Pseudomonas aeruginosa adapts to octenidine via a combination of efflux and membrane remodelling

Lucy J. Bock*, Philip M. Ferguson, Maria Clarke, Vichayanee Pumpitakkul, Matthew E. Wand, Paul Enguerrand Fady, Leanne Allison, Roland A. Fleck, Matthew J. Shepherd, A. James Mason, J. Mark Sutton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen capable of stably adapting to the antiseptic octenidine by an unknown mechanism. Here we characterise this adaptation, both in the laboratory and a simulated clinical setting, and identify a novel antiseptic resistance mechanism. In both settings, 2 to 4-fold increase in octenidine tolerance was associated with stable mutations and a specific 12 base pair deletion in a putative Tet-repressor family gene (smvR), associated with a constitutive increase in expression of the Major Facilitator Superfamily (MFS) efflux pump SmvA. Adaptation to higher octenidine concentrations led to additional stable mutations, most frequently in phosphatidylserine synthase pssA and occasionally in phosphatidylglycerophosphate synthase pgsA genes, resulting in octenidine tolerance 16- to 256-fold higher than parental strains. Metabolic changes were consistent with mitigation of oxidative stress and altered plasma membrane composition and order. Mutations in SmvAR and phospholipid synthases enable higher level, synergistic tolerance of octenidine.

Original languageEnglish
Article number1058
JournalCommunications Biology
Volume4
Issue number1
DOIs
Publication statusPublished - 9 Sep 2021

Bibliographical note

Funding Information: We thank Schülke & Mayr (Norderstedt, Germany) for supplying octenidine and the SEVA community, in particular the group of Victor De Lorenzo, for supplying plasmids and protocols used and adapted in this study. We are grateful to Rose Jeeves for setting up the initial BreSeq analysis workstream. We thank Keith Poole (Queen’s University, Canada) for transposon mutants used in this study. L.J.B., M.E.W. and J.M.S. acknowledge funding from Grant-in-Aid Project number 109506 and M.J.S. from PHE’s Placement Student scheme. P.M.F. is supported by a KCL Health Schools Studentship funded by the EPSRC (EP/M50788X/1). P.F. was supported by a BBSRC LIDo iCASE studentship with Public Health England—2081638. NMR experiments described in this paper were produced using the facilities of the Centre for Biomolecular Spectroscopy, King’s College London, acquired with a Multi-user Equipment Grant from the Wellcome Trust and an Infrastructure Grant from the British Heart Foundation. This work was also supported by the Francis Crick Institute through provision of access to the MRC Biomedical NMR Centre. The Francis Crick Institute receives its core funding from Cancer Research UK (FC001029), the UK Medical Research Council (FC001029), and the Wellcome Trust (FC001029). We thank Dr Tom Frenkiel and Dr Alain Oregioni for their assistance with HR-MAS NMR experiments performed at the Francis Crick Institute. We thank Alice Hodgson-Casson for contributing the metabolic pathway cartoon.

Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Publisher Copyright: © Crown 2021

Citation: Bock, L.J., Ferguson, P.M., Clarke, M. et al. Pseudomonas aeruginosa adapts to octenidine via a combination of efflux and membrane remodelling. Commun Biol 4, 1058 (2021).

DOI: https://doi.org/10.1038/s42003-021-02566-4

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