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.
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.
| Original language | English |
|---|---|
| Article number | lxae173 |
| Journal | Journal of Applied Microbiology |
| Volume | 135 |
| Issue number | 7 |
| Early online date | 11 Jul 2024 |
| DOIs | |
| Publication status | Published - 31 Jul 2024 |
Data Availability Statement
Raw reads for parental isolates are available under BioProject accession number PRJNA554808. The complete annotated genome assembly for P. mirabilis HI4320 is available under BioProject accession number PRJNA608758.Funding
This work was primarily supported by funding from the Medical Research Council and the UK Health Security Agency as an iCASE studentship to H.P. (MR/P015956/1) and funding from the Medical Research Council GW4 Biomed DTP as a studentship to V.B. (MR/N0137941/1). B.V.J. is also supported by funding from the Dunhill Medical Trust (RPGF1906\171).
| Funders | Funder number |
|---|---|
| Health Security Agency | MR/N0137941/1, MR/P015956/1 |
| Dunhill Medical Trust | RPGF1906\171 |
Keywords
- Proteus mirabilis
- biocide tolerance
- chlorhexidine
- octenidine
- urinary tract infection
ASJC Scopus subject areas
- Biotechnology
- Applied Microbiology and Biotechnology