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tolerance

  • Gain-of-Function Mutations in Acid Stress Response (<em>evgS</em>) Protect <span class="named-content genus-species" id="named-content-1">Escherichia coli</span> from Killing by Gallium Nitrate, an Antimicrobial Candidate
    Mechanisms of Action: Physiological Effects
    Gain-of-Function Mutations in Acid Stress Response (evgS) Protect Escherichia coli from Killing by Gallium Nitrate, an Antimicrobial Candidate

    Widespread antimicrobial resistance encourages repurposing/refining of nonantimicrobial drugs for antimicrobial indications. Gallium nitrate (GaNt), an FDA-approved medication for cancer-related hypercalcemia, recently showed good activity against several clinically significant bacteria.

    Jie Zeng, Liwen Wu, Zhou Liu, Yihua Lv, Jinzhi Feng, Weijie Wang, Yunxin Xue, Dai Wang, Jiabin Li, Karl Drlica, Xilin Zhao
  • <span class="named-content genus-species" id="named-content-1">Pseudomonas aeruginosa</span> Polynucleotide Phosphorylase Controls Tolerance to Aminoglycoside Antibiotics by Regulating the MexXY Multidrug Efflux Pump
    Mechanisms of Resistance
    Pseudomonas aeruginosa Polynucleotide Phosphorylase Controls Tolerance to Aminoglycoside Antibiotics by Regulating the MexXY Multidrug Efflux Pump

    Pseudomonas aeruginosa is an opportunistic pathogen that shows high intrinsic resistance to a variety of antibiotics. The MexX-MexY-OprM efflux pump plays an important role in bacterial resistance to aminoglycoside antibiotics.

    Zheng Fan, Xiaolei Pan, Dan Wang, Ronghao Chen, Tongtong Fu, Baopeng Yang, Yongxin Jin, Fang Bai, Zhihui Cheng, Weihui Wu
  • <em>In Vitro</em> and <em>In Vivo</em> Activity, Tolerability, and Mechanism of Action of BX795 as an Antiviral against Herpes Simplex Virus 2 Genital Infection
    Antiviral Agents
    In Vitro and In Vivo Activity, Tolerability, and Mechanism of Action of BX795 as an Antiviral against Herpes Simplex Virus 2 Genital Infection

    Herpes simplex virus type 2 (HSV-2) causes recurrent lesions in the anogenital area that may be transmitted through sexual encounters. Nucleoside analogs, such as acyclovir (ACV), are currently prescribed clinically to curb this infection. However, in some cases, reduced efficacy has been observed due to the emergence of resistance against these drugs. In our previous study, we reported the discovery of a novel anti-HSV-1 small molecule...

    James Hopkins, Tejabhiram Yadavalli, Rahul Suryawanshi, Farreh Qatanani, Ipsita Volety, Ram Koganti, Aqsa Iqbal, Deepak Shukla
  • Investigating the Effects of Osmolytes and Environmental pH on Bacterial Persisters
    Susceptibility
    Investigating the Effects of Osmolytes and Environmental pH on Bacterial Persisters

    Bacterial persisters are phenotypic variants that temporarily demonstrate an extraordinary tolerance toward antibiotics. Persisters have been linked to the recalcitrance of biofilm-related infections; hence, a complete understanding of their physiology can lead to improvement of therapeutic strategies for such infections. Mechanisms pertaining to persister formation are thought to be associated with stress response pathways triggered by...

    Prashant Karki, Sayed Golam Mohiuddin, Pouria Kavousi, Mehmet A. Orman
  • <span class="named-content genus-species" id="named-content-1">Encephalitozoon cuniculi</span> Genotype III Evinces a Resistance to Albendazole Treatment in both Immunodeficient and Immunocompetent Mice
    Experimental Therapeutics
    Encephalitozoon cuniculi Genotype III Evinces a Resistance to Albendazole Treatment in both Immunodeficient and Immunocompetent Mice

    Of four genotypes of Encephalitozoon cuniculi, E. cuniculi genotype II is considered to represent a parasite that occurs in many host species in a latent asymptomatic form, whereas E. cuniculi genotype III seems to be more...

    Bohumil Sak, Klára Brdíčková, Nikola Holubová, Dana Květoňová, Lenka Hlásková, Martin Kváč
  • Determining the Development of Persisters in Extensively Drug-Resistant <span class="named-content genus-species" id="named-content-1">Acinetobacter baumannii</span> upon Exposure to Polymyxin B-Based Antibiotic Combinations Using Flow Cytometry
    Susceptibility
    Determining the Development of Persisters in Extensively Drug-Resistant Acinetobacter baumannii upon Exposure to Polymyxin B-Based Antibiotic Combinations Using Flow Cytometry

    Polymyxin B-based combinations are increasingly prescribed as a last-line option against extensively drug-resistant (XDR) Acinetobacter baumannii. It is unknown if such combinations can result in the development of nondividing persister cells in XDR A. baumannii. We investigated persister...

    Fiona Hui-Sian Wong, Yiying Cai, Hui Leck, Tze-Peng Lim, Jocelyn Qi-Min Teo, Winnie Lee, Tse Hsien Koh, Thuan Tong Tan, Kar Wai Tan, Andrea Lay-Hoon Kwa
  • CreC Sensor Kinase Activation Enhances Growth of <span class="named-content genus-species" id="named-content-1">Escherichia coli</span> in the Presence of Cephalosporins and Carbapenems
    Mechanisms of Resistance
    CreC Sensor Kinase Activation Enhances Growth of Escherichia coli in the Presence of Cephalosporins and Carbapenems

    Mutants with enhanced growth in the presence of an antibiotic are more difficult to identify than mutants where the antibiotic’s MIC increases, because they are not amenable to lethal selection in vitro. We report that activatory mutations in the CreC signal sensor enhance growth of Escherichia coli in the presence of cefoxitin, cefotaxime, and meropenem,...

    Yuiko Takebayashi, Emma S. Taylor, Sam Whitwam, Matthew B. Avison
  • Spheroplast-Mediated Carbapenem Tolerance in Gram-Negative Pathogens
    Mechanisms of Resistance
    Spheroplast-Mediated Carbapenem Tolerance in Gram-Negative Pathogens

    Antibiotic tolerance, the ability to temporarily sustain viability in the presence of bactericidal antibiotics, constitutes an understudied and yet potentially widespread cause of antibiotic treatment failure. We have previously shown that the Gram-negative pathogen Vibrio cholerae can tolerate exposure to the typically bactericidal β-lactam antibiotics by assuming a...

    Trevor Cross, Brett Ransegnola, Jung-Ho Shin, Anna Weaver, Kathy Fauntleroy, Michael S. VanNieuwenhze, Lars F. Westblade, Tobias Dörr
  • A First-in-Human Safety, Tolerability, and Pharmacokinetics Study of Benapenem in Healthy Chinese Volunteers
    Clinical Therapeutics
    A First-in-Human Safety, Tolerability, and Pharmacokinetics Study of Benapenem in Healthy Chinese Volunteers

    The objective of this trial was to investigate the safety, tolerability, and pharmacokinetics (PK) of benapenem administered by single or multiple intravenous infusions in healthy Chinese volunteers. The trial was divided into 3 parts.

    Cai-Yun Zhao, Yuan Lv, Yan Zhu, Min-Ji Wei, Meng-Ying Liu, Xi-Wei Ji, Zi-Sheng Kang, Ya-Hong Xia, Ji-Hong Tian, Yan Ma, Yan Liu
  • Mechanisms of Resistance
    Impact of Bacterial Membrane Fatty Acid Composition on the Failure of Daptomycin To Kill Staphylococcus aureus
    Rym Boudjemaa, Clément Cabriel, Florence Dubois-Brissonnet, Nicolas Bourg, Guillaume Dupuis, Alexandra Gruss, Sandrine Lévêque-Fort, Romain Briandet, Marie-Pierre Fontaine-Aupart, Karine Steenkeste

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