Response of Pseudomonas aeruginosa to the innate immune system-derived oxidants hypochlorous acid and hypothiocyanous acid
File(s)
Published version
Author(s)
Farrant, Katie V
Spiga, Livia
Davies, Jane C
Williams, Huw
Type
Journal Article
Abstract
Pseudomonas aeruginosa is a significant nosocomial pathogen and associated with lung infections in cystic fibrosis (CF). Once established, P. aeruginosa infections persist and are rarely eradicated despite host immune cells producing antimicrobial oxidants, including hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). There is limited knowledge as to how P. aeruginosa senses, responds to, and protects itself against HOCl and HOSCN, and the contribution of such responses to its success as a CF pathogen. To investigate the P. aeruginosa response to these oxidants we screened 707 transposon mutants, with mutations in regulatory genes, for altered growth following HOCl exposure. We identified regulators of antibiotic resistance, methionine biosynthesis and catabolite repression, and PA14_07340, the homologue of the Escherichia coli HOCl-sensor RclR (30% identical), that are required for protection against HOCl. We have shown that RclR (PA14_07340) protects specifically against HOCl and HOSCN stress, and responds to both oxidants by upregulating expression of a putative peroxiredoxin, rclX (PA14_07355). Transcriptional analysis revealed that while there was specificity in the response to HOCl (231 genes upregulated) and HOSCN (105 genes upregulated) there was considerable overlap, with 74 genes upregulated by both oxidants. These included genes encoding the type III secretion system, sulphur and taurine transport, and the MexEF-OprN efflux pump. RclR coordinates part of the response to both oxidants, including upregulation of pyocyanin biosynthesis genes, and in the presence of HOSCN, downregulation of chaperone genes. These data indicate that the P. aeruginosa response to HOCl and HOSCN is multifaceted, with RclR playing an essential role.
Date Issued
2021-01-01
Date Acceptance
2020-10-08
Citation
Journal of Bacteriology, 2021, 203 (2)
ISSN
0021-9193
Publisher
American Society for Microbiology
Journal / Book Title
Journal of Bacteriology
Volume
203
Issue
2
Copyright Statement
© 2020 Farrant et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/).
License URL
Sponsor
Cystic Fibrosis Trust
Grant Number
SRC 014
Subjects
Science & Technology
Life Sciences & Biomedicine
Microbiology
Pseudomonas aeruginosa
cystic fibrosis
efflux pumps
hypochlorous acid
hypothiocyanous acid
oxidative stress
peroxiredoxin
TUBERCULOSIS ALKYLHYDROPEROXIDASE AHPD
MULTIDRUG EFFLUX SYSTEM
MEXE-MEXF-OPRN
ESCHERICHIA-COLI
TRANSCRIPTION FACTOR
ALIPHATIC SULFONATES
GENE-CLUSTER
HOST-DEFENSE
REGULATOR
EXPRESSION
Pseudomonas aeruginosa
cystic fibrosis
efflux pumps
hypochlorous acid
hypothiocyanous acid
oxidative stress
peroxiredoxin
06 Biological Sciences
07 Agricultural and Veterinary Sciences
11 Medical and Health Sciences
Microbiology
Publication Status
Published
Article Number
ARTN e00300
Date Publish Online
2020-10-26