Regulating polymyxin resistance in Gram-negative bacteria: roles of two-component systems PhoPQ and PmrAB

Author:

Huang Jiayuan1,Li Chen23,Song Jiangning2,Velkov Tony4,Wang Lushan5,Zhu Yan1,Li Jian1

Affiliation:

1. Biomedicine Discovery Institute & Department of Microbiology, Monash University, Melbourne 3800, Australia

2. Biomedicine Discovery Institute & Department of Biochemistry & Molecular Biology, Monash University, Melbourne 3800, Australia

3. Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich 8093, Switzerland

4. Department of Pharmacology & Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Melbourne 3010, Australia

5. State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China

Abstract

Polymyxins (polymyxin B and colistin) are last-line antibiotics against multidrug-resistant Gram-negative pathogens. Polymyxin resistance is increasing worldwide, with resistance most commonly regulated by two-component systems such as PmrAB and PhoPQ. This review discusses the regulatory mechanisms of PhoPQ and PmrAB in mediating polymyxin resistance, from receiving an external stimulus through to activation of genes responsible for lipid A modifications. By analyzing the reported nonsynonymous substitutions in each two-component system, we identified the domains that are critical for polymyxin resistance. Notably, for PmrB 71% of resistance-conferring nonsynonymous mutations occurred in the HAMP (present in histidine kinases, adenylate cyclases, methyl accepting proteins and phosphatase) linker and DHp (dimerization and histidine phosphotransfer) domains. These results enhance our understanding of the regulatory mechanisms underpinning polymyxin resistance and may assist with the development of new strategies to minimize resistance emergence.

Publisher

Future Medicine Ltd

Subject

Microbiology (medical),Microbiology

Reference115 articles.

1. Gram-Negative Bacterial Infections: Research Priorities, Accomplishments, and Future Directions of the Antibacterial Resistance Leadership Group

2. World Health Organization. Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug resistant bacterial infections, including tuberculosis. EMP/IAU/201712 (2017). www.who.int/medicines/areas/rational_use/prioritization-of-pathogens/en

3. Polymyxin: Alternative Mechanisms of Action and Resistance

4. Pharmacology of polymyxins: new insights into an ‘old’ class of antibiotics

5. Mechanisms of resistance to membrane-disrupting antibiotics in Gram-positive and Gram-negative bacteria

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