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Perspective | Clinical Science and EpidemiologyDo an Altered Gut Microbiota and an Associated Leaky Gut Affect COVID-19 Severity?Coronavirus disease 2019 (COVID-19), which has been declared a pandemic, has exhibited a wide range of severity worldwide. Although this global variation is largely affected by socio-medical situations in each country, there is also high individual-level variation attributable to elderliness and certain underlying medical conditions, including high blood pressure, diabetes, and obesity.
Perspective | Host-Microbe BiologyThe Balance of Neutrophil Extracellular Trap Formation and Nuclease Degradation: an Unknown Role of Bacterial Coinfections in COVID-19 Patients?Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to public health crises worldwide. An understanding of the pathogenesis and the development of treatment strategies is of high interest. Recently, neutrophil extracellular traps (NETs) have been identified as a potential driver of severe SARS-CoV-2 infections in humans. NETs are extracellular DNA fibers released by neutrophils after contact with various stimuli and...
Opinion/Hypothesis
Opinion/Hypothesis | Host-Microbe BiologyIs It Time To Kill the Survival Curve? A Case for Disease Progression Factors in Microbial Pathogenesis and Host Defense ResearchThe molecular mechanisms of microbial virulence and host defense are most often studied using animal models and Koch’s molecular postulates. A common rationale for these types of experiments is to identify therapeutic targets based on the assumption that microbial or host factors that confer extreme animal model survival phenotypes represent critical virulence and host defense factors.
Minireviews
Minireview | Host-Microbe BiologySame Game, Different Players: Emerging Pathogens of the CF LungIncidences of non-tuberculosis mycobacteria (NTM) and Aspergillus fumigatus have increased around the world over the past decade and have become a significant health threat to immunocompromised individuals such as those with cystic fibrosis (CF). CF is characterized by the buildup of mucus in the lungs which become chronically infected by a myriad of pathogens.
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Minireview | Host-Microbe BiologyMechanisms of Attenuation by Genetic Recoding of VirusesThe development of safe and effective vaccines against viruses is central to disease control. With advancements in DNA synthesis technology, the production of synthetic viral genomes has fueled many research efforts that aim to generate attenuated viruses by introducing synonymous mutations.
Minireview | Host-Microbe BiologyPreserve a Voucher Specimen! The Critical Need for Integrating Natural History Collections in Infectious Disease StudiesDespite being nearly 10 months into the COVID-19 (coronavirus disease 2019) pandemic, the definitive animal host for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causal agent of COVID-19, remains unknown. Unfortunately, similar problems exist for other betacoronaviruses, and no vouchered specimens exist to corroborate host species identification for most of these pathogens.
Minireview | Host-Microbe BiologyCoronaviruses Associated with the Superfamily MusteloideaAmong the animal superfamily Musteloidea, which includes those commonly known as mustelids, naturally occurring and species-specific alphacoronavirus infections have been observed in both mink (Mustela vison/Neovison vison) and domestic ferrets (...
Observations
Observation | Host-Microbe BiologySterilization by Adaptive Immunity of a Conditionally Persistent Mutant of Mycobacterium tuberculosisThe bacterial pathogen Mycobacterium tuberculosis can enter into a persistent state in which M. tuberculosis can evade host immunity, thereby reducing the effectiveness of current tuberculosis vaccines. Understanding the factors that contribute to persistence would enable the rational design of...
Observation | Clinical Science and EpidemiologyColistin Heteroresistance Is Largely Undetected among Carbapenem-Resistant Enterobacterales in the United StatesHeteroresistance is an underappreciated phenomenon that may be the cause of some unexplained antibiotic treatment failures. Misclassification of heteroresistant isolates as susceptible may lead to inappropriate therapy.
Observation | Molecular Biology and PhysiologyAntibiotic-Selected Gene Amplification Heightens Metal ResistanceTo inhibit bacterial transmission and infection, health care facilities use bactericidal metal coatings to prevent colonization of surfaces and implanted devices. In these environments, antibiotics are commonly used, but their effect on metal resistance is unclear.
Observation | Host-Microbe BiologyPhospholipid Metabolism Is Associated with Time to HIV Rebound upon Treatment InterruptionThe likelihood of HIV rebound after stopping antiretroviral therapy (ART) is a combination of the size of HIV reservoirs that persist despite ART and the host immunological and inflammatory factors that control these reservoirs. Therefore, there is a need to comprehensively understand these host factors to develop a strategy to cure HIV infection and prevent viral rebound post-ART.
Observation | Therapeutics and PreventionTiny Earth: A Big Idea for STEM Education and Antibiotic DiscoveryThe world faces two seemingly unrelated challenges—a shortfall in the STEM workforce and increasing antibiotic resistance among bacterial pathogens. We address these two challenges with Tiny Earth, an undergraduate research course that excites students about science and creates a pipeline for antibiotic discovery.
Observation | Therapeutics and PreventionAntifungal Liposomes Directed by Dectin-2 Offer a Promising Therapeutic Option for Pulmonary AspergillosisInvasive aspergillosis (IA) generally results from a pulmonary infection of immunocompromised patients by the common soil organism and opportunistic pathogen Aspergillus fumigatus. The susceptible population has expanded rapidly due to the increased number of cancer patients with immunocompromising chemotherapy and transplant patients taking immunosuppressants.
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Research Articles
Research Article | Applied and Environmental ScienceMicrobial Functional Responses Explain Alpine Soil Carbon Fluxes under Future Climate ScenariosThe warming pace in the Tibetan Plateau, which is predominantly occupied by grassland ecosystems, has been 0.2°C per decade in recent years, dwarfing the rate of global warming by a factor of 2. Many Earth system models project substantial carbon sequestration in Tibet, which has been observed.
Research Article | Host-Microbe BiologyZn2+ Intoxication of Mycobacterium marinum during Dictyostelium discoideum Infection Is Counteracted by Induction of the Pathogen Zn2+ Exporter CtpCMicroelements are essential for the function of the innate immune system. A deficiency in zinc or copper results in an increased susceptibility to bacterial infections.
Research Article | Host-Microbe BiologyStep-Specific Adaptation and Trade-Off over the Course of an Infection by GASP Mutation Small Colony VariantsWithin-host evolution has been described in many bacterial diseases, and the genetic basis behind the adaptations has stimulated a lot of interest. Yet, the studied adaptations are generally focused on antibiotic resistance and rarely on the adaptation to the environment given by the host, and the potential trade-offs hindering adaptations to each step of the infection are rarely considered.
Research Article | Host-Microbe BiologyAtypical Ebola Virus Disease in a Nonhuman Primate following Monoclonal Antibody Treatment Is Associated with Glycoprotein Mutations within the Fusion Loop...Ebola virus remains a global threat to public health and biosecurity, yet we still know relatively little about its pathogenesis and the complications that arise following recovery. With nearly 20,000 survivors from the 2013–2016 West African outbreak, as well as over 1,000 survivors of the recent outbreak in the DRC, we must consider the consequences of virus persistence and recrudescent disease, even if they are rare.
Research Article | Host-Microbe BiologyRanDeL-Seq: a High-Throughput Method to Map Viral cis- and trans-Acting ElementsRecent studies have renewed interest in developing novel antiviral therapeutics and vaccines based on defective interfering particles (DIPs)—a subset of viral deletion mutants that conditionally replicate. Identifying and engineering DIPs require that viral cis- and trans-acting elements be accurately mapped.
Research Article | Host-Microbe BiologyNrf2 Regulates Granuloma Formation and Macrophage Activation during Mycobacterium avium Infection via Mediating Nramp1 and HO-1 ExpressionsNontuberculous mycobacteria (NTM) are an important cause of morbidity and mortality in pulmonary infections. Among them, Mycobacterium avium complex (MAC) is the most common cause of pulmonary NTM disease worldwide.
Research Article | Host-Microbe BiologyA Trap-Door Mechanism for Zinc Acquisition by Streptococcus pneumoniae AdcAZinc is an essential nutrient for the virulence of bacterial pathogens such as Streptococcus pneumoniae. Many Gram-positive bacteria use a two-domain lipoprotein for zinc acquisition, but how this class of metal-recruiting proteins acquire zinc and interact with the uptake machinery has remained poorly defined.
Research Article | Molecular Biology and PhysiologyThe Compact Macronuclear Genome of the Ciliate Halteria grandinella: A Transcriptome-Like Genome with 23,000 NanochromosomesHow to achieve protein diversity by genome and transcriptome processing is essential for organismal complexity and adaptation. The present work identifies that the macronuclear genome of Halteria grandinella, a cosmopolitan unicellular eukaryote, is composed almost entirely of gene-sized nanochromosomes with extremely short nongenic regions.
Research Article | Host-Microbe BiologyIntracellular Group A Streptococcus Induces Golgi Fragmentation To Impair Host Defenses through Streptolysin O and NAD-GlycohydrolaseTwo prominent virulence factors of group A Streptococcus (GAS), streptolysin O (SLO) and NAD-glycohydrolase (Nga), are linked to enhanced pathogenicity of the prevalent GAS strains. Recent advances show that SLO and Nga are important for intracellular survival of GAS in epithelial cells and macrophages.
Research Article | Host-Microbe BiologyExperimental Human Challenge Defines Distinct Pneumococcal Kinetic Profiles and Mucosal Responses between Colonized and Non-Colonized AdultsOccurrence of lower respiratory tract infections requires prior colonization of the upper respiratory tract with a pathogen. Most bacterial infection and colonization studies have been performed in murine and in vitro models due to the current invasive sampling methodology of the upper respiratory tract, both of which poorly reflect the complexity of host-pathogen interactions in the human nose.
Research Article | Host-Microbe BiologyToxoplasma gondii Extends the Life Span of Infected Human Neutrophils by Inducing Cytosolic PCNA and Blocking Activation of Apoptotic CaspasesToxoplasma gondii is an obligate intracellular parasite that can cause life-threatening disease in immunocompromised individuals and in the developing fetus. Interestingly, T. gondii has evolved strategies to successfully manipulate the host immune system to establish a productive infection and...
Research Article | Therapeutics and PreventionA Combination of Anti-PD-L1 Treatment and Therapeutic Vaccination Facilitates Improved Retroviral Clearance via Reactivation of Highly Exhausted T CellsDespite significant efforts, vaccines are not yet available for every infectious pathogen, and the search for a protective approach to prevent the establishment of chronic infections, i.e., with HIV, continues. Immune checkpoint therapies targeting inhibitory receptors, such as PD-1, have shown impressive results against solid tumors.
Research Article | Molecular Biology and PhysiologyFunctional Differences between E. coli and ESKAPE Pathogen GroES/GroELThe GroES/GroEL chaperonin from E. coli has long served as the model system for other chaperonins. This assumption seemed valid because of the high conservation between the chaperonins.
Research Article | Molecular Biology and PhysiologySeptal Class A Penicillin-Binding Protein Activity and ld-Transpeptidases Mediate Selection of Colistin-Resistant Lipooligosaccharide-Deficient Acinetobacter baumanniiThe increasing prevalence of antibiotic treatment failure associated with Gram-negative bacterial infections highlights an urgent need to develop new alternative therapeutic strategies. The last-line antimicrobial colistin (polymyxin E) targets the ubiquitous outer membrane lipopolysaccharide (LPS)/LOS membrane anchor, lipid A, which is essential for viability of most diderms.
Research Article | Molecular Biology and PhysiologyZ-Ring-Associated Proteins Regulate Clustering of the Replication Terminus-Binding Protein ZapT in Caulobacter crescentusRapidly growing bacteria experience dynamic changes in chromosome architecture during chromosome replication and segregation, reflecting the importance of mechanisms that organize the chromosome globally and locally within a cell to maintain faithful transmission of genetic material across generations. During cell division in the model bacterium Caulobacter crescentus...
Research Article | Host-Microbe BiologyIntracellular Density of Wolbachia Is Mediated by Host Autophagy and the Bacterial Cytoplasmic Incompatibility Gene cifB in a Cell Type-Dependent Manner in Drosophila melanogasterAutophagy is a eukaryotic intracellular degradation pathway which can act as an innate immune response to eliminate pathogens. Conversely, pathogens can evolve proteins which modulate the autophagy pathway to subvert degradation and establish an infection. Wolbachia, a vertically transmitted obligate endosymbiont which infects up to 40% of insect species, is negatively regulated by autophagy in whole animals, but the specific...
Research Article | Molecular Biology and PhysiologyPorZ, an Essential Component of the Type IX Secretion System of Porphyromonas gingivalis, Delivers Anionic Lipopolysaccharide to the PorU Sortase for Transpeptidase Processing of T9SS Cargo ProteinsBacteria have evolved multiple systems to transport effector proteins to their surface or into the surrounding milieu. These proteins have a wide range of functions, including attachment, motility, nutrient acquisition, and toxicity in the host. Porphyromonas gingivalis, the human pathogen responsible for severe gum diseases (periodontitis), uses a recently...
Research Article | Therapeutics and PreventionPneumococcal Conjugate Vaccine Protection against Coronavirus-Associated Pneumonia Hospitalization in Children Living with and without HIVSARS-CoV-2 may cause severe hospitalization, but little is known about the role of secondary bacterial infection in these severe cases, beyond the observation of high levels of reported inflammatory markers, associated with bacterial infection, such as procalcitonin. We did a secondary analysis of a double-blind randomized trial of pneumococcal conjugate vaccine (PCV) to examine its impact on human coronavirus (CoV) infections before...
Research Article | Molecular Biology and PhysiologySignal Recognition Particle Suppressor Screening Reveals the Regulation of Membrane Protein Targeting by the Translation RateInner membrane proteins (IMPs) are cotranslationally inserted into the inner membrane or endoplasmic reticulum by the signal recognition particle (SRP). Generally, the deletion of SRP can result in protein targeting defects in Escherichia coli.
Research Article | Host-Microbe BiologyHemozoin Promotes Lung Inflammation via Host Epithelial ActivationRespiratory distress (RD) is a complication of severe malaria associated with a particularly high risk for death in African children infected with the parasite Plasmodium falciparum. The pathophysiology underlying RD remains poorly understood, and the condition is managed supportively.
Editor's Pick Research Article | Therapeutics and PreventionPeptide-Conjugated Phosphorodiamidate Morpholino Oligomers Retain Activity against Multidrug-Resistant Pseudomonas aeruginosa In Vitro and In VivoNumerous Gram-negative bacteria are becoming increasingly resistant to multiple, if not all, classes of existing antibiotics. Multidrug-resistant Pseudomonas aeruginosa bacteria are a major cause of health care-associated infections in a variety of clinical settings, endangering patients who are immunocompromised or those who suffer from chronic infections, such as...
Research Article | Host-Microbe BiologyQuantifying Absolute Neutralization Titers against SARS-CoV-2 by a Standardized Virus Neutralization Assay Allows for Cross-Cohort Comparisons of COVID-19 SeraVaccines and antibody-based therapeutics like convalescent-phase plasma therapy are premised upon inducing or transferring neutralizing antibodies that inhibit SARS-CoV-2 entry into cells. Virus neutralization assays (VNAs) for measuring neutralizing antibody titers (NATs) are an essential part of determining vaccine or therapeutic efficacy.
Research Article | Host-Microbe BiologyCRNKL1 Is a Highly Selective Regulator of Intron-Retaining HIV-1 and Cellular mRNAsTo regulate its complex splicing pattern, HIV-1 uses the adaptor protein Rev to shuttle unspliced or partially spliced mRNA from the nucleus to the cytoplasm. In the absence of Rev, these RNAs are retained in the nucleus, but it is unclear why.
Research Article | Host-Microbe BiologyMolecular Signatures of Inflammatory Profile and B-Cell Function in Patients with Severe Fever with Thrombocytopenia SyndromeSFTSV is an emerging virus discovered in China in 2009; it has since spread to other countries in East Asia. Although the fatality rates of SFTSV infection range from 5.3% to as high as 27%, the mechanisms underlying clinical manifestations are largely unknown.
Research Article | Host-Microbe BiologySalmonella enterica Serovar Typhimurium Exploits Cycling through Epithelial Cells To Colonize Human and Murine EnteroidsPathogenic gut bacteria are common causes of intestinal disease. Enteroids—cultured three-dimensional replicas of the mammalian gut—offer an emerging model system to study disease mechanisms under conditions that recapitulate key features of the intestinal tract.
Research Article | Host-Microbe BiologyPlasmodium falciparum Guanylyl Cyclase-Alpha and the Activity of Its Appended P4-ATPase Domain Are Essential for cGMP Synthesis and Blood-Stage EgressThe clinical manifestations of malaria arise due to successive rounds of replication of Plasmodium parasites within red blood cells. Once mature, daughter merozoites are released from infected erythrocytes to invade new cells in a tightly regulated process termed egress.
Research Article | Clinical Science and EpidemiologyGenome Sequencing of Sewage Detects Regionally Prevalent SARS-CoV-2 VariantsViral genome sequencing has guided our understanding of the spread and extent of genetic diversity of SARS-CoV-2 during the COVID-19 pandemic. SARS-CoV-2 viral genomes are usually sequenced from nasopharyngeal swabs of individual patients to track viral spread.
Research Article | Therapeutics and PreventionApmA Is a Unique Aminoglycoside Antibiotic Acetyltransferase That Inactivates ApramycinApramycin is an aminoglycoside antibiotic that has been traditionally used in veterinary medicine. Recently, it has become an attractive candidate to repurpose in the fight against multidrug-resistant pathogens prioritized by the World Health Organization.
Research Article | Host-Microbe BiologyNatural Bacterial Assemblages in Arabidopsis thaliana Tissues Become More Distinguishable and Diverse during Host Development...Developing synthetic microbial communities that can increase plant yield or deter pathogens requires basic research on several fronts, including the efficiency with which microbes colonize plant tissues, how plant genes shape the microbiome, and the microbe-microbe interactions involved in community assembly. Findings on each of these fronts depend upon the spatial and temporal scales at which plant microbiomes are surveyed.
Research Article | Applied and Environmental ScienceAcetylene-Fueled Trichloroethene Reductive Dechlorination in a Groundwater Enrichment CultureUnderstanding the complex metabolisms of microbial communities in contaminated groundwaters is a challenge. PCE and TCE are among the most common groundwater contaminants in the United States that, when exposed to certain minerals, exhibit a unique abiotic degradation pathway in which C2H2 is a product.
Research Article | Ecological and Evolutionary ScienceCompetition Sensing Changes Antibiotic Production in StreptomycesBacteria secrete antibiotics to inhibit their competitors, but the presence of competitors can determine whether these toxins are produced. Here, we study the role of the competitive and resource environment on antibiotic production in Streptomyces, bacteria renowned for their production of antibiotics.
Research Article | Ecological and Evolutionary ScienceEvolutionary Trajectory of the Replication Mode of Bacterial RepliconsChromosome replication is an essential process for cell division. The mode of chromosome replication has important impacts on the structure of the chromosome and replication speed.
Research Article | Host-Microbe BiologyEngineering a Reliable and Convenient SARS-CoV-2 Replicon System for Analysis of Viral RNA Synthesis and Screening of Antiviral InhibitorsCOVID-19 has caused a severe global pandemic. Until now, there has been no simple and reliable system available in a lower-biosafety-grade laboratory for SARS-CoV-2 virologic research and inhibitor screening.
Research Article | Ecological and Evolutionary ScienceAt Least Seven Distinct Rotavirus Genotype Constellations in Bats with Evidence of Reassortment and Zoonotic TransmissionsThe increased research on bat coronaviruses after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) allowed the very rapid identification of SARS-CoV-2. This is an excellent example of the importance of knowing viruses harbored by wildlife in general, and bats in particular, for global preparedness against emerging viral pathogens.
Research Article | Applied and Environmental ScienceMetabolic Exchange and Energetic Coupling between Nutritionally Stressed Bacterial Species: Role of Quorum-Sensing MoleculesBacteria have usually been studied in single culture in rich media or under specific starvation conditions. However, in nature they coexist with other microorganisms and build an advanced society.
Research Article | Host-Microbe BiologyPartial Prion Cross-Seeding between Fungal and Mammalian Amyloid Signaling MotifsAmyloids are β-sheet-rich protein polymers that can be pathological or display a variety of biological roles. In filamentous fungi, specific immune receptors activate programmed cell death execution proteins through a process of amyloid templating akin to prion propagation.
Research Article | Therapeutics and PreventionPredictive Rules of Efflux Inhibition and Avoidance in Pseudomonas aeruginosaEfflux pump avoidance and inhibition are desired properties for the optimization of antibacterial activities against Gram-negative bacteria. However, molecular and physicochemical interactions defining the interface between compounds and efflux pumps remain poorly understood. We identified properties that correlate with efflux avoidance and inhibition, are predictive of similar features in structurally diverse compounds, and allow...
Research Article | Ecological and Evolutionary ScienceCytoplasmic Incompatibility Variations in Relation with Wolbachia cid Genes Divergence in Culex pipiensCulex pipiens mosquitoes are infected with wPip. These endosymbionts induce a conditional sterility called CI resulting from embryonic deaths, which constitutes a cornerstone for Wolbachia antivectorial methods.
Research Article | Molecular Biology and PhysiologyTrehalose Recycling Promotes Energy-Efficient Biosynthesis of the Mycobacterial Cell EnvelopeThe mycomembrane layer of the mycobacterial cell envelope is a barrier to environmental, immune, and antibiotic insults. There is considerable evidence of mycomembrane plasticity during infection and in response to host-mimicking stresses.
Research Article | Therapeutics and PreventionAntibody Landscape Analysis following Influenza Vaccination and Natural Infection in Humans with a High-Throughput Multiplex Influenza Antibody Detection AssayRepeated influenza vaccination and natural infections generate complex immune profiles in humans that require antibody landscape analysis to assess immunity and evaluate vaccines. However, antibody landscape analyses are difficult to perform using traditional assays.
Research Article | Host-Microbe BiologyChlamydia trachomatis TmeA Directly Activates N-WASP To Promote Actin Polymerization and Functions Synergistically with TarP during InvasionThe increasing genetic tractability of Chlamydia trachomatis is accelerating the ability to characterize the unique infection biology of this obligate intracellular parasite. These efforts are leading to a greater understanding of the molecular events associated with key virulence requirements.
Research Article | Host-Microbe BiologyDistinct Roles of Two DNA Methyltransferases from Cryphonectria parasitica in Fungal Virulence, Responses to Hypovirus Infection, and Viral ClearanceAlthough relatively few in number, studies of DNA methylation have shown that fungal DNA methylation is implicated in development, genome integrity, and genome defense. While fungal DNMTase has been suggested as playing a role in genome defense, studies of the biological function of fungal DNMTase have been very limited.
Research Article | Host-Microbe BiologySARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the SpikeWith the ongoing pandemic, it is critical to understand how natural immunity against SARS-CoV-2 and COVID-19 develops. We have identified that subjects with more severe COVID-19 disease mount a more robust and neutralizing antibody response against SARS-CoV-2 spike protein.
Research Article | Molecular Biology and PhysiologyNoc Corrals Migration of FtsZ Protofilaments during Cytokinesis in Bacillus subtilisIn bacteria, a condensed structure of FtsZ (Z-ring) recruits cell division machinery at the midcell, and Z-ring formation is discouraged over the chromosome by a poorly understood phenomenon called nucleoid occlusion. In B. subtilis, nucleoid occlusion has been reported to be mediated, at least in part, by the DNA-membrane bridging protein, Noc.
Research Article | Clinical Science and EpidemiologyAtypical Divergence of SARS-CoV-2 Orf8 from Orf7a within the Coronavirus Lineage Suggests Potential Stealthy Viral Strategies in Immune EvasionOrf8 is one of the most puzzling genes in the SARS lineage of coronaviruses, including SARS-CoV-2. Using sophisticated sequence comparisons, we confirm its origins from Orf7a, another gene in the lineage that appears as more conserved, compared to Orf8.
Research Article | Molecular Biology and PhysiologyA Bacterial Toxin Perturbs Intracellular Amino Acid Balance To Induce PersistenceTo overcome various environmental challenges, bacterial cells can enter a physiologically quiescent state, known as dormancy or persistence, which balances growth and viability. In this study, we report a new mechanism by which a toxin-antitoxin system responds to harsh environmental conditions or nutrient deprivation by orchestrating a dormant state while preserving viability.
Research Article | Therapeutics and PreventionStructural Characterization of Diazabicyclooctane β-Lactam “Enhancers” in Complex with Penicillin-Binding Proteins PBP2 and PBP3 of Pseudomonas aeruginosaAntibiotic resistance is a significant clinical problem. Developing novel antibiotics that overcome known resistance mechanisms is highly desired.
Research Article | Host-Microbe BiologyBiogeography of the Relationship between the Child Gut Microbiome and Innate Immune SystemBoth the gut microbiome and innate immunity are known to differ across biogeographically diverse human populations. The gut microbiome has been shown to directly influence systemic immunity in animal models.
Research Article | Ecological and Evolutionary ScienceFitness Cost Evolution of Natural Plasmids of Staphylococcus aureusPlasmids are major agents in the spread of antibiotic resistance genes among bacteria. How plasmids and their hosts coevolve to reduce the fitness cost associated with plasmid carriage when bacteria grow in an antibiotic-free environment is not well understood.
Research Article | Ecological and Evolutionary ScienceCompetitive Exclusion and Metabolic Dependency among Microorganisms Structure the Cellulose Economy of an Agricultural SoilOur study reveals the ecogenomic traits of microorganisms participating in the cellulose economy of soil. We identified three major categories of participants in this economy: (i) independent primary degraders, (ii) interdependent primary degraders, and (iii) secondary consumers (mutualists, opportunists, and parasites).
Research Article | Host-Microbe BiologyDirect Intracellular Visualization of Ebola Virus-Receptor Interaction by In Situ Proximity LigationEbola virus causes episodic but increasingly frequent outbreaks of severe disease in Middle Africa, as shown by the recently overcome second largest outbreak on record in the Democratic Republic of Congo. Despite considerable effort, FDA-approved antifiloviral therapeutics or targeted interventions are not available yet.
Research Article | Molecular Biology and PhysiologyNovel Biological Functions of the NsdC Transcription Factor in Aspergillus fumigatusAspergillus fumigatus is an opportunistic human fungal pathogen and the main causal agent of invasive aspergillosis, a life-threatening infection especially in immunocompromised patients. A. fumigatus can undergo both asexual and sexual reproductive cycles, and the regulation of both cycles involves...
Research Article | Host-Microbe BiologyHyaluronidase Impairs Neutrophil Function and Promotes Group B Streptococcus Invasion and Preterm Labor in Nonhuman PrimatesGroup B streptococci (GBS) are bacteria that commonly reside in the female lower genital tract as asymptomatic members of the microbiota. However, during pregnancy, GBS can infect tissues at the maternal-fetal interface, leading to preterm birth, stillbirth, or fetal injury.
Research Article | Molecular Biology and PhysiologyTranscriptomic, Protein-DNA Interaction, and Metabolomic Studies of VosA, VelB, and WetA in Aspergillus nidulans Asexual SporesFilamentous fungi produce a vast number of asexual spores that act as efficient propagules. Due to their infectious and/or allergenic nature, fungal spores affect our daily life. Aspergillus species produce asexual spores called conidia; their formation involves morphological development and metabolic changes, and the associated regulatory systems are coordinated by multiple transcription factors (TFs).
Research Article | Ecological and Evolutionary ScienceConvergent Adaptation to Quantitative Host Resistance in a Major Plant PathogenUnderstanding the genetic basis of pathogen adaptation to quantitative resistance in plants has a key role to play in establishing durable strategies for resistance deployment. In this context, a population genomic approach was developed for a major plant pathogen (the fungus Pseudocercospora fijiensis causing black leaf streak disease of banana) whereby samples from new resistant banana hybrids were compared with samples from...
Research Article | Ecological and Evolutionary ScienceMultiple Pathways to Homothallism in Closely Related Yeast Lineages in the BasidiomycotaSexual reproduction is important for the biology of eukaryotes because it strongly impacts the dynamics of genetic variation. In fungi, although sexual reproduction is usually associated with the fusion between cells belonging to different individuals (heterothallism), sometimes a single individual is capable of completing the sexual cycle alone (homothallism).
Research Article | Host-Microbe BiologyPersistence of Human Bocavirus 1 in Tonsillar Germinal Centers and Antibody-Dependent Enhancement of InfectionHuman bocavirus 1 (HBoV1), a common pediatric respiratory pathogen, can persist in airway secretions for months hampering diagnosis. It also persists in tonsils, providing potential reservoirs for airway shedding, with the exact location, host cell types, and virus activity unknown.
Research Article | Host-Microbe BiologyMechanistic Analysis of the Broad Antiretroviral Resistance Conferred by HIV-1 Envelope Glycoprotein MutationsAlthough combination antiretroviral (ARV) therapy is highly effective in controlling the progression of HIV disease, drug resistance can be a major obstacle. Recent findings suggest that resistance can develop without ARV target gene mutations.
Research Article | Host-Microbe BiologySirtuin 3 Downregulation in Mycobacterium tuberculosis-Infected Macrophages Reprograms Mitochondrial Metabolism and Promotes Cell DeathTuberculosis, the disease caused by the bacterium M. tuberculosis, remains one of the top 10 causes of death worldwide. Macrophages, the first cells to encounter M. tuberculosis and critical for defense against infection, are hijacked by...
Research Article | Host-Microbe BiologySphingomyelin Biosynthesis Is Essential for Phagocytic Signaling during Mycobacterium tuberculosis Host Cell EntryMycobacterium tuberculosis (Mtb) invades alveolar macrophages through phagocytosis to establish infection and cause disease. The molecular mechanisms underlying Mtb entry are still poorly understood.
Research Article | Molecular Biology and PhysiologyCarbon Catabolite Repression in Filamentous Fungi Is Regulated by Phosphorylation of the Transcription Factor CreAIn filamentous fungi, the transcription factor CreA controls carbohydrate metabolism through the regulation of genes encoding enzymes required for the use of alternative carbon sources. In this work, phosphorylation sites were identified on Aspergillus nidulans CreA, and subsequently, the two newly identified sites S268 and T308, the previously identified but...
Research Article | Molecular Biology and PhysiologyTgIF2K-B Is an eIF2α Kinase in Toxoplasma gondii That Responds to Oxidative Stress and Optimizes PathogenicityToxoplasma gondii is a single-celled parasite that infects nucleated cells of warm-blooded vertebrates, including one-third of the human population. The parasites are not cleared by the immune response and persist in the host by converting into a latent tissue cyst form.
Research Article | Clinical Science and EpidemiologyStreptococcus pyogenes Is Associated with Idiopathic Cutaneous Ulcers in Children on a Yaws-Endemic IslandCutaneous ulcers (CU) affect approximately 100,000 children in the tropics each year. While two-thirds of CU are caused by Treponema pallidum subspecies pertenue and Haemophilus ducreyi, the cause(s) of the remaining one-third is unknown.
Editor's Pick Research Article | Host-Microbe BiologyHow Phagocytic Cells Kill Different Bacteria: a Quantitative Analysis Using Dictyostelium discoideumPhagocytic cells ingest and kill bacteria, a process essential for the defense of the human body against infections. Many potential killing mechanisms have been identified in phagocytic cells, including free radicals, toxic ions, enzymes, and permeabilizing peptides.
Research Article | Applied and Environmental ScienceMetagenomic Quantification of Genes with Internal StandardsqPCR and metagenomics are central molecular techniques that have offered insights into biological processes for decades, from monitoring spatial and temporal gene dynamics to tracking ARGs or pathogens. Still needed is a tool that can quantify thousands of relevant genes in a sample as gene copies per sample mass or volume.
Research Article | Therapeutics and PreventionMonoclonal Antibodies against Zika Virus NS1 Protein Confer Protection via Fcγ Receptor-Dependent and -Independent PathwaysZika virus (ZIKV) is a mosquito-borne flavivirus that has been linked to congenital microcephaly during recent epidemics. No licensed antiviral drug or vaccine is available.
Research Article | Host-Microbe BiologyCharacterization of a Four-Component Regulatory System Controlling Bacteriocin Production in Streptococcus gallolyticusStreptococcus gallolyticus subsp. gallolyticus, formerly known as Streptococcus bovis biotype I, is an opportunistic pathogen causing septicemia and endocarditis in the elderly often associated with asymptomatic colonic neoplasia. Recent studies indicate that...
Research Article | Clinical Science and EpidemiologyGenomic Drivers of Multidrug-Resistant Shigella Affecting Vulnerable Patient Populations in the United States and AbroadMultidrug-resistant Shigella isolates with resistance to macrolides are an emerging public health threat. We define a plasmid/pathogen complex behind infections seen in the United States and globally in vulnerable patient populations and identify multiple outbreaks in the United States and evidence of intercontinental transmission.
Research Article | Host-Microbe BiologySecretion, Maturation, and Activity of a Quorum Sensing Peptide (GSP) Inducing Bacteriocin Transcription in Streptococcus gallolyticusStreptococcus gallolyticus subsp. gallolyticus is an opportunistic pathogen associated with colorectal cancer (CRC) and endocarditis. S. gallolyticus subsp. gallolyticus utilizes quorum sensing (QS) to regulate the production of a bacteriocin (gallocin) and gain a selective...
Research Article | Clinical Science and EpidemiologyCharacterization of SARS-CoV-2 RNA, Antibodies, and Neutralizing Capacity in Milk Produced by Women with COVID-19Results from prior studies assaying human milk for the presence of SARS-CoV-2, the causative virus of COVID-19, have suggested milk may act as a potential vehicle for mother-to-child transmission. Most previous studies are limited because they followed only a few participants, were cross-sectional, and/or failed to report how milk was collected and/or analyzed.
Research Article | Molecular Biology and Physiology(p)ppGpp/GTP and Malonyl-CoA Modulate Staphylococcus aureus Adaptation to FASII Antibiotics and Provide a Basis for Synergistic Bi-TherapyStaphylococcus aureus is a major human bacterial pathogen for which new inhibitors are urgently needed. Antibiotic development has centered on the fatty acid synthesis (FASII) pathway, which provides the building blocks for bacterial membrane phospholipids.
Research Article | Therapeutics and PreventionDevelopment of DNA Vaccine Targeting E6 and E7 Proteins of Human Papillomavirus 16 (HPV16) and HPV18 for Immunotherapy in Combination with Recombinant Vaccinia Boost and PD-1 AntibodyPersistent expression of high-risk human papillomavirus (HPV) E6 and E7 is an obligate driver for several human malignancies, including cervical cancer, wherein HPV16 and HPV18 are the most common types. PD-1 antibody immunotherapy helps a subset of cervical cancer patients, and its efficacy might be improved by combination with active vaccination against E6 and/or E7.
Research Article | Therapeutics and PreventionPuf4 Mediates Post-transcriptional Regulation of Cell Wall Biosynthesis and Caspofungin Resistance in Cryptococcus neoformansCryptococcus neoformans is an environmental fungus that causes pulmonary and central nervous system infections. It is also responsible for 15% of AIDS-related deaths.
Research Article | Host-Microbe BiologyExploring the Impact of Ketodeoxynonulosonic Acid in Host-Pathogen Interactions Using Uptake and Surface Display by Nontypeable Haemophilus influenzaeAll cells in vertebrates are coated with a dense array of glycans often capped with sugars called sialic acids. Sialic acids have many functions, including serving as a signal for recognition of “self” cells by the immune system, thereby guiding an appropriate immune response against foreign “nonself” and/or damaged cells.
Research Article | Host-Microbe Biology5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal EpitheliumAn expansion of Enterobacterales in the fecal microbiota is a microbial signature of dysbiosis that is linked to many noncommunicable diseases, including ulcerative colitis. Here, we used Escherichia coli, a representative of the Enterobacterales, to show that its dysbiotic expansion during colitis can be remediated by modulating host epithelial...
Research Article | Host-Microbe BiologyThe Canonical Long-Chain Fatty Acid Sensing Machinery Processes Arachidonic Acid To Inhibit Virulence in Enterohemorrhagic Escherichia coliPolyunsaturated fatty acids (PUFAs) play important roles in host immunity. Manipulation of lipid content in host tissues through diet or pharmacological interventions is associated with altered severity of various inflammatory diseases.
Research Article | Molecular Biology and PhysiologyEvaluation of Microbe-Driven Soil Organic Matter Quantity and Quality by Thermodynamic TheoryMicrobial communities are known to be important drivers of organic matter (OM) accumulation in terrestrial ecosystems. However, despite the importance of these soil microbes and processes, the mechanisms behind these microbial-SOM associations remain poorly understood.
Research Article | Molecular Biology and PhysiologyFlagellar Perturbations Activate Adhesion through Two Distinct Pathways in Caulobacter crescentusUnderstanding how bacteria colonize solid surfaces is of significant clinical, industrial and ecological importance. In this study, we identified genes that are required for Caulobacter crescentus to activate surface attachment in response to signals from a macromolecular machine called the flagellum.
Research Article | Molecular Biology and PhysiologyHistone Modifications in Papillomavirus Virion MinichromosomesA relatively unique feature of papillomaviruses is that the viral genome is associated with host histones inside the virion. However, little is known about the nature of the epigenome within papillomavirions or its biological relevance to the infectious viral cycle.
Editor's Pick Research Article | Host-Microbe BiologyUnraveling the Impact of Secreted Proteases on Hypervirulence in Staphylococcus aureusA key feature of the pathogenic success of S. aureus is the myriad virulence factors encoded within its genome. These are subject to multifactorial control, ensuring their timely production only within an intended infectious niche.
Research Article | Molecular Biology and PhysiologyMolecular Basis of the Versatile Regulatory Mechanism of HtrA-Type Protease AlgW from Pseudomonas aeruginosaHtrA-family proteases are commonly employed to sense the protein folding stress and activate the regulated intramembrane proteolysis (RIP) cascade in Gram-negative bacteria. Here, we reveal the unique dual-signal activation and dynamic regulation properties of AlgW, an HtrA-type protease triggering the AlgU stress-response pathway, which controls alginate production and mucoid conversion in...
Research Article | Molecular Biology and PhysiologyPlasticity of the Influenza Virus H5 HA ProteinThe HA protein of influenza A viruses is the major viral antigen. In this study, we simultaneously introduced mutations at 17 amino acid positions of an H5 HA expected to affect antigenicity. Viruses with ≥13 amino acid changes in HA were viable, and some had altered antigenic properties. H5 HA can therefore accommodate many mutations in regions that affect antigenicity. The substantial plasticity of H5 HA may facilitate the emergence...
Research Article | Host-Microbe BiologyAn Antibiotic-Impacted Microbiota Compromises the Development of Colonic Regulatory T Cells and Predisposes to Dysregulated Immune ResponsesThe assembly of microbial communities that populate all mucosal surfaces of the human body begins right after birth. This process is prone to disruption as newborns and young infants are increasingly exposed to antibiotics, both deliberately for therapeutic purposes, and as a consequence of transmaternal exposure.
Research Article | Ecological and Evolutionary ScienceEvolution in Long-Term Stationary-Phase Batch Culture: Emergence of Divergent Escherichia coli Lineages over 1,200 DaysBacteria have remarkable metabolic capabilities and adaptive plasticity, enabling them to survive in changing environments. In nature, bacteria spend a majority of their time in a state of slow growth or maintenance, scavenging nutrients for survival.
Research Article | Molecular Biology and PhysiologyGenetic Evidence for SecY Translocon-Mediated Import of Two Contact-Dependent Growth Inhibition (CDI) ToxinsMany bacterial species interact via direct cell-to-cell contact using CDI systems, which provide a mechanism to inject toxins that inhibit bacterial growth into one another. Here, we find that two CDI toxins, one that depolarizes membranes and another that degrades RNA, exploit the universally conserved SecY translocon machinery used to export proteins for target cell entry.
Research Article | Host-Microbe BiologyA Novel Trichomonas vaginalis Surface Protein Modulates Parasite Attachment via Protein:Host Cell Proteoglycan InteractionThe ability of the sexually transmitted parasite Trichomonas vaginalis to adhere to its human host is critical for establishing and maintaining an infection. Yet how parasites adhere to host cells is poorly understood.
Research Article | Molecular Biology and PhysiologyRegulatory Effects of CsrA in Vibrio choleraeVibrio cholerae, a Gram-negative bacterium, is a natural inhabitant of the aqueous environment. However, once ingested, this bacterium can colonize the human host and cause the disease cholera.
Research Article | Molecular Biology and PhysiologyPseudomonas aeruginosa Uses c-di-GMP Phosphodiesterases RmcA and MorA To Regulate Biofilm MaintenanceRecent advances in our understanding of c-di-GMP signaling have provided key insights into the regulation of biofilms. Despite an improved understanding of how biofilms initially form, the processes that facilitate the long-term maintenance of these multicellular communities remain opaque.
Research Article | Host-Microbe BiologyIL-27 Negatively Regulates Tip-DC Development during InfectionTNF/iNOS-producing dendritic cells (Tip-DCs) are at the front line as immune effector cells to fight off a broad range of invading microbes. Excessive development of Tip-DCs contributes to tissue destruction.
Research Article | Host-Microbe BiologyA Novel Enterococcus faecalis Heme Transport Regulator (FhtR) Senses Host Heme To Control Its Intracellular HomeostasisEnterococcus faecalis, a normal and harmless colonizer of the human intestinal flora can cause severe infectious diseases in immunocompromised patients, particularly those that have been heavily treated with antibiotics. Therefore, it is important to understand the factors that promote its resistance and its virulence....
Research Article | Host-Microbe BiologyPhytotoxic Tryptoquialanines Produced In Vivo by Penicillium digitatum Are Exported in Extracellular VesiclesDuring the postharvest period, citrus fruits can be affected by phytopathogens such as Penicillium digitatum, which causes green mold disease and is responsible for up to 90% of total citrus losses. Chemical fungicides are widely used to prevent green mold disease, leading to concerns about environmental and health risks.
Research Article | Host-Microbe BiologyIn Vivo Transcriptome of Lactobacillus acidophilus and Colonization Impact on Murine Host Intestinal Gene ExpressionTo date, our basis for comprehending the probiotic mechanisms of Lactobacillus acidophilus, one of the most widely consumed probiotic microbes, was largely limited to in vitro functional genomic studies. Using a germfree murine colonization model, in vivo-based transcriptional studies provided the first view of how...
Editor's Pick Research Article | Host-Microbe BiologyA Phosphonate Natural Product Made by Pantoea ananatis is Necessary and Sufficient for the Hallmark Lesions of Onion Center RotPantoea ananatis is a significant plant pathogen that targets a number of important crops, a problem that is compounded by the absence of effective treatments to prevent its spread. Our identification of pantaphos as the key virulence factor in onion center rot suggests a variety of approaches that could be employed to address this significant plant disease.
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Research Article | Molecular Biology and PhysiologyLight Signaling Regulates Aspergillus niger Biofilm Formation by Affecting Melanin and Extracellular Polysaccharide BiosynthesisAs an important industrial filamentous fungus, Aspergillus niger can perceive light. The link between light signaling and A. niger biofilm is worthy of further study since reports are lacking in this area.
Research Article | Molecular Biology and PhysiologyA Grad-seq View of RNA and Protein Complexes in Pseudomonas aeruginosa under Standard and Bacteriophage Predation ConditionsStable complexes by cellular proteins and RNA molecules lie at the heart of gene regulation and physiology in any bacterium of interest. It is therefore crucial to globally determine these complexes in order to identify and characterize new molecular players and regulation mechanisms.
Research Article | Host-Microbe BiologySARS-CoV-2 Genomic Variation in Space and Time in Hospitalized Patients in PhiladelphiaUnderstanding how SARS-CoV-2 spreads globally and within infected individuals is critical to the development of mitigation strategies. We found that most lineages in Philadelphia had resembled sequences from New York, suggesting infection primarily but not exclusively from this location.
Editor's Pick Research Article | Host-Microbe BiologyAn Indispensable Role for the MavE Effector of Legionella pneumophila in Lysosomal EvasionIntracellular proliferation of Legionella pneumophila within a vacuole in human alveolar macrophages is essential for manifestation of Legionnaires’ pneumonia. Intravacuolar growth of the pathogen is totally dependent on remodeling the L. pneumophila-containing vacuole (LCV) by the ER and on its...
Research Article | Host-Microbe BiologyViral Interactions and Pathogenesis during Multiple Viral Infections in Agaricus bisporusHow viruses interact in a multiple-virus infection was examined by quantifying the levels of 18 viral RNAs in fruiting cultures of the agriculturally cultivated fungus Agaricus bisporus and statistically analyzing and modeling their abundance. Synergistic, antagonistic, and neutral interactions occurred simultaneously in cultures.
Research Article | Host-Microbe BiologyRole of Two Metacaspases in Development and Pathogenicity of the Rice Blast Fungus Magnaporthe oryzaeMagnaporthe oryzae causes rice blast disease that threatens global food security by resulting in the severe loss of rice production every year. A tightly regulated life cycle allows M. oryzae to disarm the host plant immune system during its biotrophic stage before triggering plant cell death in its necrotrophic stage.
Research Article | Host-Microbe BiologyWolbachia and Virus Alter the Host Transcriptome at the Interface of Nucleotide Metabolism PathwaysRecently developed arbovirus control strategies leverage the symbiotic bacterium Wolbachia, which spreads in insect populations and blocks viruses from replicating. While this strategy has been successful, details of how this “pathogen blocking” works are limited. Here, we use a combination of virus infections, fly genetics, and transcriptomics to show that Wolbachia and virus interact at host nucleotide metabolism...
Research Article | Therapeutics and PreventionTargeting of Mammalian Glycans Enhances Phage Predation in the Gastrointestinal TractInvasive pathobionts or microbes capable of causing disease can reside deep within the mucosal epithelium of our gastrointestinal tract. Targeted effective antibacterial therapies are needed to combat these disease-causing organisms, many of which may be multidrug resistant.
Research Article | Clinical Science and EpidemiologyTracking the Emergence of Azithromycin Resistance in Multiple Genotypes of Typhoidal SalmonellaIn the early 1900s, with mortality of ∼30%, typhoid and paratyphoid (caused by Salmonella Typhi and Paratyphi A) ravaged parts of the world; with improved water, sanitation, and hygiene in resource-rich countries and the advent of antimicrobials, mortality dwindled to <1%. Today, the burden rests disproportionately on South Asia, where the primary means for combatting the disease is antimicrobials.
Research Article | Therapeutics and PreventionEvolution of Antibiotic Tolerance Shapes Resistance Development in Chronic Pseudomonas aeruginosa InfectionsOver the past decades, pan-resistant strains of major bacterial pathogens have emerged and have rendered clinically available antibiotics ineffective, putting at risk many of the major achievements of modern medicine, including surgery, cancer therapy, and organ transplantation. A thorough understanding of processes leading to the development of antibiotic resistance in human patients is thus urgently needed.
Research Article | Therapeutics and PreventionResistance to a Nucleoside Analog Antiviral Drug from More Rapid Extension of Drug-Containing PrimersWhile resistance to antiviral drugs can hinder their clinical use, understanding resistance mechanisms can illuminate how these drugs and their targets act. We studied a substitution in the human cytomegalovirus (HCMV) DNA polymerase that confers resistance to a leading anti-HCMV drug, ganciclovir.
Research Article | Therapeutics and PreventionStenoparib, an Inhibitor of Cellular Poly(ADP-Ribose) Polymerase, Blocks Replication of the SARS-CoV-2 and HCoV-NL63 Human Coronaviruses In VitroNew therapeutics are urgently needed in the fight against COVID-19. Repurposing drugs that are either already approved for human use or are in advanced stages of the approval process can facilitate more rapid advances toward this goal.
Research Article | Host-Microbe BiologyHuman Herpesvirus 6B U26 Inhibits the Activation of the RLR/MAVS Signaling PathwayHHV-6B (human herpesvirus 6B) is well known to evade host antiviral responses and establish a lifelong latent infection. How HHV-6B evades RNA recognition is still poorly understood. Our results indicate that HHV-6 U26 plays a vital role in RLR/MAVS signaling pathway activity. Knockout of endogenous MAVS could facilitate HHV-6B replication. The findings in this study could provide new insights into host-virus interactions and help...
Research Article | Host-Microbe BiologyHBV Core Protein Is in Flux between Cytoplasmic, Nuclear, and Nucleolar CompartmentsHBV is an endemic virus. More than 250 million people suffer from chronic HBV infection and about 800,000 die from HBV-associated disease each year.
Research Article | Host-Microbe BiologyBrachypodium Phenylalanine Ammonia Lyase (PAL) Promotes Antiviral Defenses against Panicum mosaic virus and Its SatellitesAlthough the role of plant defense mechanisms against viruses are relatively well studied in dicots and in incompatible plant-microbe interactions, studies of their roles in compatible interactions and in grasses are lagging behind. In this study, we leveraged the emerging grass model Brachypodium and genetic resources to dissect Panicum mosaic virus (PMV)- and its satellite virus (SPMV)-compatible grass-virus...
Research Article | Molecular Biology and PhysiologyParameters Affecting Continuous In Vitro Culture of Treponema pallidum StrainsSyphilis is caused by the bacterium Treponema pallidum subsp. pallidum. Until recently, this pathogen could only be maintained through infection of rabbits or other animals, making study of this important human pathogen challenging and costly. T. pallidum subsp. pallidum has now...
Research Article | Therapeutics and PreventionPrime-Pull Immunization with a Bivalent M-Protein and Spy-CEP Peptide Vaccine Adjuvanted with CAF®01 Liposomes Induces Both Mucosal and Peripheral Protection from covR/S Mutant Streptococcus pyogenesA vaccine to control S. pyogenes infection is desperately warranted. S. pyogenes colonizes the upper respiratory tract (URT) and skin, from where it can progress to invasive and immune-mediated diseases.
Research Article | Host-Microbe BiologyHerpes Simplex Virus 1 Manipulates Host Cell Antiviral and Proviral DNA Damage ResponsesWe investigated the relationship between the DNA damage response, a collection of vital cellular pathways that repair potentially lethal damage to the genome, and the DNA virus herpes simplex virus 1. We found that infection by the virus triggers the DNA damage response and key proteins that mediate this response have opposing effects on the replication and production of progeny viruses.
Editor's Pick Research Article | Host-Microbe BiologyA Heterogeneously Expressed Gene Family Modulates the Biofilm Architecture and Hypoxic Growth of Aspergillus fumigatusThe manipulation of microbial biofilms in industrial and clinical applications remains a difficult task. The problem is particularly acute with regard to filamentous fungal biofilms for which molecular mechanisms of biofilm formation, maintenance, and function are only just being elucidated.
Research Article | Host-Microbe BiologyType I Interferon Signaling Is a Common Factor Driving Streptococcus pneumoniae and Influenza A Virus Shedding and TransmissionRespiratory tract infections are a leading cause of childhood mortality and, globally, Streptococcus pneumoniae is the leading cause of mortality due to pneumonia. Transmission of S. pneumoniae primarily occurs through direct contact with respiratory secretions, although the host and bacterial...
Research Article | Molecular Biology and PhysiologyToward a Comprehensive Analysis of Posttranscriptional Regulatory Networks: a New Tool for the Identification of Small RNA Regulators of Specific mRNAsWith the recognition of the importance of posttranscriptional regulation mediated by bacterial small RNAs (sRNAs), their contribution to global gene expression regulatory networks needs to be addressed in a truly comprehensive manner. While a single sRNA targets multiple RNAs, an mRNA can be regulated by multiple sRNAs that can be either transcribed individually or derived by processing of mRNAs.
Research Article | Host-Microbe BiologyA Glycoprotein Mutation That Emerged during the 2013–2016 Ebola Virus Epidemic Alters Proteolysis and Accelerates Membrane FusionThe 2013–2016 outbreak of Ebola virus disease in West Africa demonstrated the potential for previously localized outbreaks to turn into regional, or even global, health emergencies. With over 28,000 cases and 11,000 confirmed deaths, this outbreak was over 50 times as large as any previously recorded.
Editor's Pick Research Article | Therapeutics and PreventionMutations in the Hemagglutinin Stalk Domain Do Not Permit Escape from a Protective, Stalk-Based Vaccine-Induced Immune Response in the Mouse ModelBroadly protective or universal influenza virus vaccines target viral epitopes that appear to be conserved. However, it is unclear whether the virus will be able to escape once immunological pressure is applied to these epitopes through vaccination of large proportions of the population. Studies that investigate the fitness and antigenic characteristics of viruses that escape immunological pressure on these conserved epitopes are...
Research Article | Host-Microbe BiologyIdentification and Molecular Dissection of IMC32, a Conserved Toxoplasma Inner Membrane Complex Protein That Is Essential for Parasite ReplicationThe IMC is an important organelle that apicomplexan parasites use to maintain their intracellular lifestyle. While many IMC proteins have been identified, only a few central players that are essential for internal budding have been described and even fewer are conserved across the phylum.
Editor's Pick Research Article | Clinical Science and EpidemiologyEvolutionary Dynamics Based on Comparative Genomics of Pathogenic Escherichia coli Lineages Harboring Polyketide Synthase (pks) IslandExtraintestinal pathologies caused by highly virulent strains of E. coli amount to clinical implications with high morbidity and mortality rates. Pathogenic E. coli strains are evolving with the horizontal acquisition of mobile genetic elements, including pathogenicity islands such as the pks...
Research Article | Clinical Science and EpidemiologyComorbidities in SARS-CoV-2 Patients: a Systematic Review and Meta-AnalysisCOVID-19 has plagued the world since it was first identified in December 2019. Previous systematic reviews and meta-analysis were limited by various factors such as the usage of non-peer reviewed data and were also limited by the lack of clinical data on a global scale.
Research Article | Host-Microbe BiologyHigh-Resolution Differentiation of Enteric Bacteria in Premature Infant Fecal Microbiomes Using a Novel rRNA AmpliconAchieving strain-level resolution is a major obstacle for source tracking and temporal studies of microbiomes. In this study, we describe a novel deep-sequencing approach that provides species- and strain-level resolution of the neonatal microbiome.
Research Article | Molecular Biology and PhysiologyA Novel Mode of Photoprotection Mediated by a Cysteine Residue in the Chlorophyll Protein IsiACyanobacteria, oxygenic photosynthetic microbes, constantly experience varying light regimes. Light intensities higher than those that saturate the photosynthetic capacity of the organism often lead to redox damage to the photosynthetic apparatus and often cell death.
Research Article | Host-Microbe BiologyDiscovery of Bacterial Fimbria–Glycan Interactions Using Whole-Cell Recombinant Escherichia coli ExpressionUnderstanding the tropism of pathogens for host and tissue requires a complete understanding of the host receptors targeted by fimbrial adhesins. Furthermore, blocking adhesion is a promising strategy to counter increasing antibiotic resistance and is enabled by the identification of host receptors.
Editor's Pick Research Article | Molecular Biology and PhysiologySubcellular Architecture of the xyl Gene Expression Flow of the TOL Catabolic Plasmid of Pseudomonas putida mt-2The transfer of information between DNA, RNA, and proteins in a bacterium is often compared to the decoding of a piece of software in a computer. However, the tridimensional layout and the relational logic of the cognate biological hardware, i.e., the nucleoid, the RNA polymerase, and the ribosomes, are habitually taken for granted.
Research Article | Molecular Biology and PhysiologyCryoelectron Microscopy Structures of AdeB Illuminate Mechanisms of Simultaneous Binding and Exporting of SubstratesAcinetobacter baumannii has emerged as one of the most highly antibiotic-resistant Gram-negative pathogens. The prevalent AdeB multidrug efflux pump mediates resistance to a broad spectrum of clinically relevant antimicrobial agents.
Research Article | Host-Microbe BiologyReal-Time Imaging of Polioviral RNA Translocation across a MembraneThe initial transfer of genomic material from a virus into a host cell is a key step in any viral infection. Consequently, understanding how viruses deliver their genomes into cells could reveal attractive therapeutic targets.
Editor's Pick Research Article | Host-Microbe BiologyPreconceptual Priming Overrides Susceptibility to Escherichia coli Systemic Infection during PregnancyPregnancy makes women especially vulnerable to infection. The most common cause of bloodstream infection during pregnancy is by a bacterium called Escherichia coli.
Research Article | Molecular Biology and PhysiologyTopoisomerase 2β Induces DNA Breaks To Regulate Human Papillomavirus ReplicationHigh-risk human papillomaviruses (HPVs) infect epithelial cells and induce viral genome amplification upon differentiation. HPV proteins activate DNA damage repair pathways by inducing high numbers of DNA breaks in both viral and cellular DNAs.
Research Article | Therapeutics and PreventionBacteriophage Treatment Rescues Mice Infected with Multidrug-Resistant Klebsiella pneumoniae ST258...Infections caused by multidrug-resistant K. pneumoniae pose a serious threat to at-risk patients and present a therapeutic challenge for clinicians. Bacteriophage (phage) therapy is an alternative treatment approach that has been associated with positive clinical outcomes when administered experimentally to patients with refractory bacterial infections.
Errata
Commentaries
Invasive mold infections caused by molds other than Aspergillus spp. or Mucorales are emerging. The reported prevalences of infection due to these rare fungal pathogens vary among geographic regions, driven by differences in climatic conditions, susceptible hosts, and diagnostic capabilities.
Many insects are intimately associated with microbial symbionts, which are passed to developing oocytes in the maternal body for ensuring vertical transmission to the next generation. Previous studies uncovered that some symbionts utilize preexisting host’s molecular and cellular machineries for targeting oocytes.
Enterococcus faecalis differs from many other common human pathogens in its physiology and in its susceptibility to antimicrobial agents. Multiresistant E. faecalis strains owe their phenotypes to a combination of intrinsic and acquired antimicrobial resistance determinants.