antibiotic resistance
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...
Research Article | Host-Microbe BiologyThe Role of IgG Subclass in Antibody-Mediated Protection against Carbapenem-Resistant Klebsiella pneumoniaeCarbapenem-resistant Klebsiella pneumoniae is an urgent public health threat that causes life-threatening infections in immunocompromised hosts. Its resistance to nearly all antibiotics necessitates novel strategies to treat it, including the use of monoclonal antibodies. Monoclonal antibodies are emerging as important adjuncts to traditional pharmaceuticals, and...
Commentary | Host-Microbe BiologyThe Unrecognized Threat of Secondary Bacterial Infections with COVID-19Coronavirus disease 2019 (COVID-19) is the greatest pandemic of our generation, with 16 million people affected and 650,000 deaths worldwide so far. One of the risk factors associated with COVID-19 is secondary bacterial pneumonia. In recent studies on COVID-19 patients, secondary bacterial infections were significantly associated with worse outcomes and death despite antimicrobial therapies. In the past, the intensive use of...
Research Article | Molecular Biology and PhysiologyThe Leader Peptide peTrpL Forms Antibiotic-Containing Ribonucleoprotein Complexes for Posttranscriptional Regulation of Multiresistance GenesLeader peptides encoded by transcription attenuators are widespread small proteins that are considered nonfunctional in trans. We found that the leader peptide peTrpL of the soil-dwelling plant symbiont Sinorhizobium meliloti is required for differential, posttranscriptional regulation of a multidrug resistance operon upon antibiotic exposure. Multiresistance...
Research Article | Therapeutics and PreventionChlorpromazine and Amitriptyline Are Substrates and Inhibitors of the AcrB Multidrug Efflux PumpEfflux pumps of the resistance nodulation-cell division (RND) superfamily are major contributors to multidrug resistance for most of the Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae,...
Research Article | Host-Microbe BiologyPersistent Legionnaires’ Disease and Associated Antibiotic Treatment Engender a Highly Disturbed Pulmonary Microbiome Enriched in Opportunistic MicroorganismsThe composition and dynamics of the lung microbiome during pneumonia are not known, although the lung microbiome might influence the severity and outcome of this infectious disease, similar to what was shown for the microbiome at other body sites. Here we report the findings of a comprehensive analysis of the lung microbiome composition of three patients with long-term pneumonia due to...
Research Article | Molecular Biology and PhysiologyLoss of Bacterial Cell Pole Stabilization in Caulobacter crescentus Sensitizes to Outer Membrane Stress and Peptidoglycan-Directed AntibioticsMaintenance of an intact cell envelope is essential for free-living bacteria to protect themselves against their environment. In the case of rod-shaped bacteria, the poles of the cell are potential weak points in the cell envelope due to the high curvature of the layers and the need to break and reform the cell envelope at the division plane as the cells divide. We have found that TipN, a factor required for correct division and cell...
Research Article | Therapeutics and PreventionTargeting Hidden Pathogens: Cell-Penetrating Enzybiotics Eradicate Intracellular Drug-Resistant Staphylococcus aureusThe increasing prevalence of antibiotic-resistant bacteria is one of the most urgent problems of our time. Staphylococcus aureus is an important human pathogen that has acquired several mechanisms to evade antibiotic treatment. In addition, S. aureus is able to invade and persist within human cells...