1. Academic Validation
  2. Identification and Characterization of the Neisseria gonorrhoeae MscS-Like Mechanosensitive Channel

Identification and Characterization of the Neisseria gonorrhoeae MscS-Like Mechanosensitive Channel

  • Infect Immun. 2018 May 22;86(6):e00090-18. doi: 10.1128/IAI.00090-18.
Zhemin Wang  # 1 Xiaomin Wang  # 2 Ping Lu 1 Chunshan Ni 1 Yuezhou Li 3 Stijn van der Veen 4 5
Affiliations

Affiliations

  • 1 Department of Microbiology and Parasitology, School of Medicine, Zhejiang University, Hangzhou, China.
  • 2 Department of Physiology, School of Medicine, Zhejiang University, Hangzhou, China.
  • 3 Department of Physiology, School of Medicine, Zhejiang University, Hangzhou, China yuezhou-li@zju.edu.cn stijnvanderveen@zju.edu.cn.
  • 4 Department of Microbiology and Parasitology, School of Medicine, Zhejiang University, Hangzhou, China yuezhou-li@zju.edu.cn stijnvanderveen@zju.edu.cn.
  • 5 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou, China.
  • # Contributed equally.
Abstract

Mechanosensitive channels are ubiquitous in bacteria and provide an essential mechanism to survive sudden exposure to a hypo-osmotic environment by the sensing and release of increased turgor pressure. No mechanosensitive channels have thus far been identified and characterized for the human-specific Bacterial pathogen Neisseria gonorrhoeae In this study, we identified and characterized the N. gonorrhoeae MscS-like mechanosensitive channel (Ng-MscS). Electrophysiological analyses by the patch clamp method showed that Ng-MscS is stretch activated and contains pressure-dependent gating properties. Further mutagenesis studies of critical residues forming the hydrophobic vapor lock showed that gain-of-function mutations in Ng-MscS inhibited Bacterial growth. Subsequent analysis of the function of Ng-MscS in N. gonorrhoeae by osmotic down-shock assays revealed that the survival of Ng-mscS deletion mutants was significantly reduced compared with that of wild-type strains, while down-shock survival was restored upon the ectopic complementation of mscS Finally, to investigate whether Ng-MscS is important for N. gonorrhoeae during infections, competition assays were performed by using a murine vaginal tract Infection model. Ng-mscS deletion mutants were outcompeted by N. gonorrhoeae wild-type strains for colonization and survival in this Infection model, highlighting that Ng-MscS contributes to in vivo colonization and survival. Therefore, Ng-MscS might be a promising target for the future development of novel antimicrobials.

Keywords

MscS; Neisseria gonorrhoeae; electrophysiology; gonococcus; host colonization; hypo-osmotic shock; patch clamp.

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