antibiotic resistance
Research Article | Molecular Biology and PhysiologyCryo-electron Microscopy Structure of the Acinetobacter baumannii 70S Ribosome and Implications for New Antibiotic DevelopmentAcinetobacter baumannii is a severe nosocomial threat largely due to its intrinsic antibiotic resistance and remarkable ability to acquire new resistance determinants. The bacterial ribosome serves as a major target for modern antibiotics and the design of new therapeutics. Here, we present cryo-EM structures of the...
Research Article | Therapeutics and PreventionTpiA is a Key Metabolic Enzyme That Affects Virulence and Resistance to Aminoglycoside Antibiotics through CrcZ in Pseudomonas aeruginosaThe increase in bacterial resistance against antibiotics imposes a severe threat to public health. It is urgent to identify new drug targets and develop novel antimicrobials. Metabolic homeostasis of bacteria plays an essential role in their virulence and resistance to antibiotics. Recent studies demonstrated that antibiotic efficacies can be improved by modulating the bacterial metabolism....
Research Article | Therapeutics and PreventionVaccine Protection against Multidrug-Resistant Klebsiella pneumoniae in a Nonhuman Primate Model of Severe Lower Respiratory Tract InfectionMultidrug-resistant bacteria continue to be a major problem worldwide, especially among individuals with significant comorbidities and other risk factors for infection. K. pneumoniae is among the leading causes of health care-associated infections, and the organism is often resistant to multiple classes of antibiotics. A carbapenem-resistant...
Research Article | Molecular Biology and PhysiologyNusG-Dependent RNA Polymerase Pausing and Tylosin-Dependent Ribosome Stalling Are Required for Tylosin Resistance by Inducing 23S rRNA Methylation in Bacillus subtilisAntibiotic resistance is a growing health concern. Resistance mechanisms have evolved that provide bacteria with a growth advantage in their natural habitat such as the soil. We determined that B. subtilis, a Gram-positive soil organism, has a mechanism of resistance to tylosin, a macrolide antibiotic commonly used in the meat industry. Tylosin induces expression of...
Research Article | Clinical Science and EpidemiologyPlasmid Dissemination and Selection of a Multidrug-Resistant Klebsiella pneumoniae Strain during Transplant-Associated Antibiotic TherapyAntibiotic-resistant bacteria are a serious threat to medically fragile patient populations. The spread of antibiotic resistance through plasmid-mediated mechanisms is of grave concern as it can lead to the conversion of endogenous patient-associated strains to difficult-to-treat pathogens.
Research Article | Therapeutics and PreventionModified Antibiotic Adjuvant Ratios Can Slow and Steer the Evolution of Resistance: Co-amoxiclav as a Case StudyAs antibiotic resistance spreads, a promising approach is to restore the effectiveness of existing drugs via coadministration with adjuvants that inhibit resistance. However, as for monotherapy, antibiotic-adjuvant therapies can select for a variety of resistance mechanisms, so it is imperative that adjuvants be used in a sustainable manner. We test whether the rate of resistance evolution can be decoupled from treatment efficacy using...
Perspective | Ecological and Evolutionary ScienceAntibiotics: Combatting Tolerance To Stop ResistanceAntibiotic resistance poses an alarming and ever-increasing threat to modern health care. Although the current antibiotic crisis is widely acknowledged, actions taken so far have proved insufficient to slow down the rampant spread of resistant pathogens. Problematically, routine screening methods and strategies to restrict therapy failure almost exclusively focus on genetic resistance, while evidence for dangers posed by other bacterial...
Research Article | Clinical Science and EpidemiologyComparative Genomics of Antibiotic-Resistant Uropathogens Implicates Three Routes for Recurrence of Urinary Tract InfectionsThe increasing antimicrobial resistance of uropathogens is challenging the continued efficacy of empiric antibiotic therapy for UTIs, which are among the most frequent bacterial infections worldwide. It has been suggested that drug-resistant uropathogens could persist in the intestine after the resolution of UTI and cause recurrences following periurethral contamination. A better understanding of the transmission dynamics between the...
Research Article | Molecular Biology and PhysiologyCell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in Listeria monocytogenesThe human pathogen Listeria monocytogenes is usually treated with high doses of β-lactam antibiotics, often combined with gentamicin. However, these antibiotics only act bacteriostatically on L. monocytogenes, and the immune system is needed to clear the infection. Therefore, individuals with a...
Research Article | Host-Microbe BiologyCommon Variants in the Glycerol Kinase Gene Reduce Tuberculosis Drug EfficacyTB control is limited in part by the length of antibiotic treatment needed to prevent recurrent disease. To probe mechanisms underlying survival under antibiotic pressure, we performed a genetic screen for M. tuberculosis mutants with altered susceptibility to treatment using the mouse model of TB. We identified multiple genes involved in a range of functions which...