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antibiotic resistance

  • Open Access
    Colistin Heteroresistance Is Largely Undetected among Carbapenem-Resistant <em>Enterobacterales</em> in the United States
    Observation | Clinical Science and Epidemiology
    Colistin Heteroresistance Is Largely Undetected among Carbapenem-Resistant Enterobacterales in the United States

    Heteroresistance 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.

    Victor I. Band, Sarah W. Satola, Richard D. Smith, David A. Hufnagel, Chris Bower, Andrew B. Conley, Lavanya Rishishwar, Suzanne E. Dale, Dwight J. Hardy, Roberto L. Vargas, Ghinwa Dumyati, Marion A. Kainer, Erin C. Phipps, Rebecca Pierce, Lucy E. Wilson, Matthew Sorensen, Erik Nilsson, I. King Jordan, Eileen M. Burd, Monica M. Farley, Jesse T. Jacob, Robert K. Ernst, David S. Weiss
  • Open Access
    Predictive Rules of Efflux Inhibition and Avoidance in <span class="named-content genus-species" id="named-content-1">Pseudomonas aeruginosa</span>
    Research Article | Therapeutics and Prevention
    Predictive Rules of Efflux Inhibition and Avoidance in Pseudomonas aeruginosa

    Efflux 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...

    Jitender Mehla, Giuliano Malloci, Rachael Mansbach, Cesar A. López, Ruslan Tsivkovski, Keith Haynes, Inga V. Leus, Sally B. Grindstaff, Robert H. Cascella, Napoleon D’Cunha, Liam Herndon, Nicolas W. Hengartner, Enrico Margiotta, Alessio Atzori, Attilio V. Vargiu, Pedro D. Manrique, John K. Walker, Olga Lomovskaya, Paolo Ruggerone, S. Gnanakaran, Valentin V. Rybenkov, Helen I. Zgurskaya
  • Open Access
    Comprehensive Genomic Investigation of Adaptive Mutations Driving the Low-Level Oxacillin Resistance Phenotype in <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span>
    Research Article | Clinical Science and Epidemiology
    Comprehensive Genomic Investigation of Adaptive Mutations Driving the Low-Level Oxacillin Resistance Phenotype in Staphylococcus aureus

    The 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...

    Stefano G. Giulieri, Romain Guérillot, Jason C. Kwong, Ian R. Monk, Ashleigh S. Hayes, Diane Daniel, Sarah Baines, Norelle L. Sherry, Natasha E. Holmes, Peter Ward, Wei Gao, Torsten Seemann, Timothy P. Stinear, Benjamin P. Howden
  • Open Access
    Genes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of <span class="named-content genus-species" id="named-content-1">Enterococcus faecalis</span>
    Editor's Pick Research Article | Molecular Biology and Physiology
    Genes Contributing to the Unique Biology and Intrinsic Antibiotic Resistance of Enterococcus faecalis

    Enterococci 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...

    Michael S. Gilmore, Rauf Salamzade, Elizabeth Selleck, Noelle Bryan, Suelen S. Mello, Abigail L. Manson, Ashlee M. Earl
  • Open Access
    Effects of Agricultural Fungicide Use on <span class="named-content genus-species" id="named-content-1">Aspergillus fumigatus</span> Abundance, Antifungal Susceptibility, and Population Structure
    Research Article | Applied and Environmental Science
    Effects of Agricultural Fungicide Use on Aspergillus fumigatus Abundance, Antifungal Susceptibility, and Population Structure

    Antibiotic 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...

    Amelia E. Barber, Jennifer Riedel, Tongta Sae-Ong, Kang Kang, Werner Brabetz, Gianni Panagiotou, Holger B. Deising, Oliver Kurzai
  • Open Access
    Na<sup>+</sup>-NQR Confers Aminoglycoside Resistance via the Regulation of <span class="sc">l-</span>Alanine Metabolism
    Research Article | Clinical Science and Epidemiology
    Na+-NQR Confers Aminoglycoside Resistance via the Regulation of l-Alanine Metabolism

    The 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...

    Ming Jiang, Su-fang Kuang, Shi-shi Lai, Song Zhang, Jun Yang, Bo Peng, Xuan-xian Peng, Zhuang-gui Chen, Hui Li
  • Open Access
    Micron Scale Spatial Measurement of the O<sub>2</sub> Gradient Surrounding a Bacterial Biofilm in Real Time
    Observation | Molecular Biology and Physiology
    Micron Scale Spatial Measurement of the O2 Gradient Surrounding a Bacterial Biofilm in Real Time

    O2 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...

    Alexander D. Klementiev, Zhaoyu Jin, Marvin Whiteley
  • Open Access
    Engineering of Long-Circulating Peptidoglycan Hydrolases Enables Efficient Treatment of Systemic <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span> Infection
    Research Article | Therapeutics and Prevention
    Engineering of Long-Circulating Peptidoglycan Hydrolases Enables Efficient Treatment of Systemic Staphylococcus aureus Infection

    Life-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...

    Anna M. Sobieraj, Markus Huemer, Léa V. Zinsli, Susanne Meile, Anja P. Keller, Christian Röhrig, Fritz Eichenseher, Yang Shen, Annelies S. Zinkernagel, Martin J. Loessner, Mathias Schmelcher
  • Open Access
    Outer Membrane Disruption Overcomes Intrinsic, Acquired, and Spontaneous Antibiotic Resistance
    Research Article | Therapeutics and Prevention
    Outer Membrane Disruption Overcomes Intrinsic, Acquired, and Spontaneous Antibiotic Resistance

    The 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...

    Craig R. MacNair, Eric D. Brown
  • Open Access
    Mechanistic Understanding Enables the Rational Design of Salicylanilide Combination Therapies for Gram-Negative Infections
    Research Article | Molecular Biology and Physiology
    Mechanistic Understanding Enables the Rational Design of Salicylanilide Combination Therapies for Gram-Negative Infections

    There 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...

    Janine N. Copp, Daniel Pletzer, Alistair S. Brown, Joris Van der Heijden, Charlotte M. Miton, Rebecca J. Edgar, Michelle H. Rich, Rory F. Little, Elsie M. Williams, Robert E. W. Hancock, Nobuhiko Tokuriki, David F. Ackerley

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