Identification of mechanisms modulating chlorhexidine and octenidine susceptibility in Proteus mirabilis

Author:

Pelling Harriet12,Bennett Vicky1,Bock Lucy J3,Wand Matthew E3,Denham Emma L1,MacFarlane Wendy M2,Sutton J Mark3,Jones Brian V1

Affiliation:

1. Department of Life Sciences, University of Bath , Bath BA2 7AY , United Kingdom

2. School of Applied Sciences, University of Brighton , Brighton BN2 4GJ , United Kingdom

3. United Kingdom Health Security Agency , Salisbury , United Kingdom

Abstract

Abstract Aims We aimed to identify mechanisms underlying the tolerance of Proteus mirabilis—a common cause of catheter associated urinary tract infection—to the clinically used biocides chlorhexidine (CHD) and octenidine (OCT). Methods and results We adapted three clinical isolates to grow at concentrations of 512 µg ml−1 CHD and 128 µg ml−1 OCT. Genetic characterization and complementation studies revealed mutations inactivating the smvR repressor and increasing smvA efflux expression were associated with adaptation to both biocides. Mutations in mipA (encoding the MltA interacting protein) were less prevalent than smvR mutations and only identified in CHD adapted populations. Mutations in the rppA response regulator were exclusive to one adapted isolate and were linked with reduced polymyxin B susceptibility and a predicted gain of function after biocide adaptation. Biocide adaptation had no impact on crystalline biofilm formation. Conclusions SmvR inactivation is a key mechanism in both CHD and OCT tolerance. MipA inactivation alone confers moderate protection against CHD, and rppA showed no direct role in either CHD or OCT susceptibility.

Funder

Medical Research Council

Dunhill Medical Trust

Publisher

Oxford University Press (OUP)

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3