In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 6 ( 2022-6-17), p. e1010581-
Abstract:
Vibrio cholerae is the etiologic agent of the severe human diarrheal disease cholera. To colonize mammalian hosts, this pathogen must defend against host-derived toxic compounds, such as nitric oxide (NO) and NO-derived reactive nitrogen species (RNS). RNS can covalently add an NO group to a reactive cysteine thiol on target proteins, a process called protein S-nitrosylation, which may affect bacterial stress responses. To better understand how V . cholerae regulates nitrosative stress responses, we profiled V . cholerae protein S-nitrosylation during RNS exposure. We identified an S-nitrosylation of cysteine 235 of AphB, a LysR-family transcription regulator that activates the expression of tcpP , which activates downstream virulence genes. Previous studies show that AphB C235 is sensitive to O 2 and reactive oxygen species (ROS). Under microaerobic conditions, AphB formed dimer and directly repressed transcription of hmpA , encoding a flavohemoglobin that is important for NO resistance of V . cholerae . We found that tight regulation of hmpA by AphB under low nitrosative stress was important for V . cholerae optimal growth. In the presence of NO, S-nitrosylation of AphB abolished AphB activity, therefore relieved hmpA expression. Indeed, non-modifiable aphB C235S mutants were sensitive to RNS in vitro and drastically reduced colonization of the RNS-rich mouse small intestine. Finally, AphB S-nitrosylation also decreased virulence gene expression via debilitation of tcpP activation, and this regulation was also important for V . cholerae RNS resistance in vitro and in the gut. These results suggest that the modulation of the activity of virulence gene activator AphB via NO-dependent protein S-nitrosylation is critical for V . cholerae RNS resistance and colonization.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010581
DOI:
10.1371/journal.ppat.1010581.g001
DOI:
10.1371/journal.ppat.1010581.g002
DOI:
10.1371/journal.ppat.1010581.g003
DOI:
10.1371/journal.ppat.1010581.g004
DOI:
10.1371/journal.ppat.1010581.g005
DOI:
10.1371/journal.ppat.1010581.g006
DOI:
10.1371/journal.ppat.1010581.s001
DOI:
10.1371/journal.ppat.1010581.s002
DOI:
10.1371/journal.ppat.1010581.s003
DOI:
10.1371/journal.ppat.1010581.s004
DOI:
10.1371/journal.ppat.1010581.s005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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