Differential regulation of the surface-exposed and secreted SslE lipoprotein in extraintestinal pathogenic Escherichia coli

Tan, Lendl, Moriel, Danilo G., Totsika, Makrina, Beatson, Scott A. and Schembri, Mark A. (2016) Differential regulation of the surface-exposed and secreted SslE lipoprotein in extraintestinal pathogenic Escherichia coli. PLoS One, 11 9: e0162391. doi:10.1371/journal.pone.0162391


 
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Author Tan, Lendl
Moriel, Danilo G.
Totsika, Makrina
Beatson, Scott A.
Schembri, Mark A.
Title Differential regulation of the surface-exposed and secreted SslE lipoprotein in extraintestinal pathogenic Escherichia coli
Formatted title
Differential regulation of the surface-exposed and secreted SslE lipoprotein in extraintestinal pathogenic Escherichia coli
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2016-09-06
Year available 2016
Sub-type Article (original research)
DOI 10.1371/journal.pone.0162391
Open Access Status DOI
Volume 11
Issue 9
Start page e0162391
Total pages 26
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Abstract Extra-intestinal pathogenic Escherichia coli (ExPEC) are responsible for diverse infections including meningitis, sepsis and urinary tract infections. The alarming rise in anti-microbial resistance amongst ExPEC complicates treatment and has highlighted the need for alternative preventive measures. SslE is a lipoprotein secreted by a dedicated type II secretion system in E. coli that was first identified as a potential vaccine candidate using reverse genetics. Although the function and protective efficacy of SslE has been studied, the molecular mechanisms that regulate SslE expression remain to be fully elucidated. Here, we show that while the expression of SslE can be detected in E. coli culture supernatants, different strains express and secrete different amounts of SslE when grown under the same conditions. While the histone-like transcriptional regulator H-NS strongly represses sslE at ambient temperatures, the variation in SslE expression at human physiological temperature suggested a more complex mode of regulation. Using a genetic screen to identify novel regulators of sslE in the high SslE-expressing strain UTI89, we defined a new role for the nucleoid-associated regulator Fis and the ribosome-binding GTPase TypA as positive regulators of sslE transcription. We also showed that Fis-mediated enhancement of sslE transcription is dependent on a putative Fis-binding sequence located upstream of the -35 sequence in the core promoter element, and provide evidence to suggest that Fis may work in complex with H-NS to control SslE expression. Overall, this study has defined a new mechanism for sslE regulation and increases our understanding of this broadly conserved E. coli vaccine antigen.
Formatted abstract
Extra-intestinal pathogenic Escherichia coli (ExPEC) are responsible for diverse infections including meningitis, sepsis and urinary tract infections. The alarming rise in anti-microbial resistance amongst ExPEC complicates treatment and has highlighted the need for alternative preventive measures. SslE is a lipoprotein secreted by a dedicated type II secretion system in E. coli that was first identified as a potential vaccine candidate using reverse genetics. Although the function and protective efficacy of SslE has been studied, the molecular mechanisms that regulate SslE expression remain to be fully elucidated. Here, we show that while the expression of SslE can be detected in E. coli culture supernatants, different strains express and secrete different amounts of SslE when grown under the same conditions. While the histone-like transcriptional regulator H-NS strongly represses sslE at ambient temperatures, the variation in SslE expression at human physiological temperature suggested a more complex mode of regulation. Using a genetic screen to identify novel regulators of sslE in the high SslE-expressing strain UTI89, we defined a new role for the nucleoid-associated regulator Fis and the ribosome-binding GTPase TypA as positive regulators of sslE transcription. We also showed that Fis-mediated enhancement of sslE transcription is dependent on a putative Fis-binding sequence located upstream of the -35 sequence in the core promoter element, and provide evidence to suggest that Fis may work in complex with H-NS to control SslE expression. Overall, this study has defined a new mechanism for sslE regulation and increases our understanding of this broadly conserved E. coli vaccine antigen.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID GNT1042651
GNT1106930
DE130101169
GNT1090456
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
 
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Created: Thu, 29 Sep 2016, 00:13:40 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences