In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 3 ( 2021-3-2), p. e1009345-
Abstract:
Sensing and responding to environmental signals is critical for bacterial pathogens to successfully infect and persist within hosts. Many bacterial pathogens sense temperature as an indication they have entered a new host and must alter their virulence factor expression to evade immune detection. Using secondary structure prediction, we identified an RNA thermosensor (RNAT) in the 5’ untranslated region (UTR) of tviA encoded by the typhoid fever-causing bacterium Salmonella enterica serovar Typhi ( S . Typhi). Importantly, tviA is a transcriptional regulator of the critical virulence factors Vi capsule, flagellin, and type III secretion system-1 expression. By introducing point mutations to alter the mRNA secondary structure, we demonstrate that the 5’ UTR of tviA contains a functional RNAT using in vitro expression, structure probing, and ribosome binding methods. Mutational inhibition of the RNAT in S . Typhi causes aberrant virulence factor expression, leading to enhanced innate immune responses during infection. In conclusion, we show that S . Typhi regulates virulence factor expression through an RNAT in the 5’ UTR of tviA . Our findings demonstrate that limiting inflammation through RNAT-dependent regulation in response to host body temperature is important for S . Typhi’s “stealthy” pathogenesis.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009345
DOI:
10.1371/journal.ppat.1009345.g001
DOI:
10.1371/journal.ppat.1009345.g002
DOI:
10.1371/journal.ppat.1009345.g003
DOI:
10.1371/journal.ppat.1009345.g004
DOI:
10.1371/journal.ppat.1009345.g005
DOI:
10.1371/journal.ppat.1009345.g006
DOI:
10.1371/journal.ppat.1009345.g007
DOI:
10.1371/journal.ppat.1009345.g008
DOI:
10.1371/journal.ppat.1009345.s001
DOI:
10.1371/journal.ppat.1009345.s002
DOI:
10.1371/journal.ppat.1009345.s003
DOI:
10.1371/journal.ppat.1009345.s004
DOI:
10.1371/journal.ppat.1009345.s005
DOI:
10.1371/journal.ppat.1009345.s006
DOI:
10.1371/journal.ppat.1009345.s007
DOI:
10.1371/journal.ppat.1009345.s008
DOI:
10.1371/journal.ppat.1009345.s009
DOI:
10.1371/journal.ppat.1009345.s010
DOI:
10.1371/journal.ppat.1009345.s011
DOI:
10.1371/journal.ppat.1009345.s012
DOI:
10.1371/journal.ppat.1009345.s013
DOI:
10.1371/journal.ppat.1009345.r001
DOI:
10.1371/journal.ppat.1009345.r002
DOI:
10.1371/journal.ppat.1009345.r003
DOI:
10.1371/journal.ppat.1009345.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
Bookmarklink