antibiotic tolerance
Research Article | Molecular Biology and PhysiologyThe Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated Streptococcus pyogenes InfectionsBiofilm-mediated bacterial infections are a major threat to human health because of their recalcitrance to antibiotic treatment. Through the study of Streptococcus pyogenes, a significant human pathogen that is known to form antibiotic-tolerant biofilms, we demonstrated the role that a bacterial pathway known for responding to acid stress plays in biofilm growth and...
Research Article | Host-Microbe BiologyThe Neutrally Charged Diarylurea Compound PQ401 Kills Antibiotic-Resistant and Antibiotic-Tolerant Staphylococcus aureusMembrane-damaging antimicrobial agents have great potential to treat multidrug-resistant or multidrug-tolerant bacteria against which conventional antibiotics are not effective. However, their therapeutic applications are often hampered due to their low selectivity to bacterial over mammalian membranes or their potential for cross-resistance to a broad spectrum of cationic membrane-active antimicrobial agents. We discovered that the...
Minireview | Therapeutics and PreventionA Physiological Basis for Nonheritable Antibiotic ResistanceAntibiotics constitute one of the cornerstones of modern medicine. However, individuals may succumb to a bacterial infection if a pathogen survives exposure to antibiotics. The ability of bacteria to survive bactericidal antibiotics results from genetic changes in the preexisting bacterial genome, from the acquisition of genes from other organisms, and from nonheritable phenomena that give rise to antibiotic tolerance. Nonheritable...
Research Article | Therapeutics and PreventionRapid Freezing Enables Aminoglycosides To Eradicate Bacterial Persisters via Enhancing Mechanosensitive Channel MscL-Mediated Antibiotic UptakeAntibiotics have long been used to successfully kill bacterial pathogens, but antibiotic resistance/tolerance usually has led to the failure of antibiotic therapy, and it has become a severe threat to human health. How to improve the efficacy of existing antibiotics is of importance for combating antibiotic-resistant/tolerant pathogens. Here, we report that 10-s rapid freezing with liquid nitrogen dramatically enhanced the bactericidal...
- Research Article | Molecular Biology and PhysiologyChlorate Specifically Targets Oxidant-Starved, Antibiotic-Tolerant Populations of Pseudomonas aeruginosa Biofilms
The anaerobic growth and survival of bacteria are often correlated with physiological tolerance to conventional antibiotics, motivating the development of novel strategies targeting pathogens in anoxic environments. A key challenge is to identify drug targets that are specific to this metabolic state. Chlorate is a nontoxic compound that can be reduced to toxic chlorite by a widespread enzyme of anaerobic metabolism. We tested the...
- Editor's Pick Research ArticleProphages and Growth Dynamics Confound Experimental Results with Antibiotic-Tolerant Persister Cells
The recalcitrance of antibiotic-tolerant persister cells is thought to cause relapsing infections and antibiotic treatment failure in various clinical setups. Previous studies identified multiple genetic pathways involved in persister formation but also revealed reproducibility problems that sparked controversies about adequate tools to study persister cells. In this study, we unraveled how typical antibiotic killing assays often fail...