antibiotic resistance
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.
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 | Clinical Science and EpidemiologyComprehensive Genomic Investigation of Adaptive Mutations Driving the Low-Level Oxacillin Resistance Phenotype in Staphylococcus aureusThe majority of Staphylococcus aureus strains causing human disease are methicillin-susceptible (MSSA) and can be treated with antistaphylococcal penicillins (such as oxacillin). While acquisition of the mec gene represents the main resistance mechanism to oxacillin, S. aureus can acquire...
Editor's Pick Research Article | Molecular Biology and PhysiologyGenes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of Enterococcus faecalisEnterococci are leading causes of antibiotic-resistant infection transmitted in hospitals. The intrinsic hardiness of these organisms allows them to survive disinfection practices and then proliferate in the gastrointestinal tracts of antibiotic-treated patients. The objective of this study was to identify the underlying genetic basis for its unusual hardiness. Using a functional genomic approach, we identified traits and pathways of...
Research Article | Applied and Environmental ScienceEffects of Agricultural Fungicide Use on Aspergillus fumigatus Abundance, Antifungal Susceptibility, and Population StructureAntibiotic resistance is an increasing threat to human health. In the case of Aspergillus fumigatus, which is an environmental fungus that also causes life-threatening infections in humans, antimicrobial resistance is suggested to arise from fungicide use in agriculture, as the chemicals used for plant protection are almost identical to the antifungals used clinically...
Research Article | Clinical Science and EpidemiologyNa+-NQR Confers Aminoglycoside Resistance via the Regulation of l-Alanine MetabolismThe Na+-NQR complex functions as a unique redox-driven sodium pump, generating membrane potential directly. However, whether it mediates generation of membrane potential indirectly is unknown. The present study shows that the Na+-NQR complex impacts membrane potential through other antiporter families Atp and Mnh. It proceeds by ATP and then cAMP/CRP regulon, which inhibits l-alanine...
Observation | Molecular Biology and PhysiologyMicron Scale Spatial Measurement of the O2 Gradient Surrounding a Bacterial Biofilm in Real TimeO2 is a fundamental environmental metabolite that affects all life on earth. While toxic to many microbes and obligately required by others, those that have appropriate physiological responses survive and can even benefit from various levels of O2, particularly in biofilm communities. Although most studies have focused on measuring O2 within biofilms, little is known about O2 gradients...
Research Article | Therapeutics and PreventionEngineering of Long-Circulating Peptidoglycan Hydrolases Enables Efficient Treatment of Systemic Staphylococcus aureus InfectionLife-threatening infections with Staphylococcus aureus are often difficult to treat due to the increasing prevalence of antibiotic-resistant bacteria and their ability to persist in protected niches in the body. Bacteriolytic enzymes are promising new antimicrobials because they rapidly kill bacteria, including drug-resistant and persisting cells, by destroying their...
Research Article | Therapeutics and PreventionOuter Membrane Disruption Overcomes Intrinsic, Acquired, and Spontaneous Antibiotic ResistanceThe spread of antibiotic resistance is an urgent threat to global health that necessitates new therapeutics. Treatments for Gram-negative pathogens are particularly challenging to identify due to the robust outer membrane permeability barrier in these organisms. Recent discovery efforts have attempted to overcome this hurdle by disrupting the outer membrane using chemical perturbants and have yielded several new peptides and small...
Research Article | Molecular Biology and PhysiologyMechanistic Understanding Enables the Rational Design of Salicylanilide Combination Therapies for Gram-Negative InfectionsThere is a critical need for more-effective treatments to combat multidrug-resistant Gram-negative infections. Combination therapies are a promising strategy, especially when these enable existing clinical drugs to be repurposed as antibiotics. We examined the mechanisms of action and basis of innate Gram-negative resistance for the anthelmintic drug niclosamide and subsequently exploited this information to demonstrate that niclosamide...