Mutation of the enterohemorrhagic escherichia coli core LPS biosynthesis enzyme RfaD confers hypersusceptibility to host intestinal innate immunity in vivo

Cheng Ju Kuo, Jenn Wei Chen, Hao Chieh Chiu, Ching Hao Teng, Tai I. Hsu, Pei Jung Lu, Wan Jr Syu, Sin Tian Wang, Ting Chen Chou, Chang Shi Chen

研究成果: Article

5 引文 (Scopus)

摘要

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important foodborne pathogen causing severe diseases in humans worldwide. Currently, there is no specific treatment available for EHEC infection and the use of conventional antibiotics is contraindicated. Therefore, identification of potential therapeutic targets and development of effective measures to control and treat EHEC infection are needed. Lipopolysaccharides (LPS) are surface glycolipids found on the outer membrane of gram-negative bacteria, including EHEC, and LPS biosynthesis has long been considered as potential anti-bacterial target. Here, we demonstrated that the EHEC rfaD gene that functions in the biosynthesis of the LPS inner core is required for the intestinal colonization and pathogenesis of EHEC in vivo. Disruption of the EHEC rfaD confers attenuated toxicity in Caenorhabditis elegans and less bacterial colonization in the intestine of C. elegans and mouse. Moreover, rfaD is also involved in the control of susceptibility of EHEC to antimicrobial peptides and host intestinal immunity. It is worth noting that rfaD mutation did not interfere with the growth kinetics when compared to the wild-type EHEC cells. Taken together, we demonstrated that mutations of the EHEC rfaD confer hypersusceptibility to host intestinal innate immunity in vivo, and suggested that targeting the RfaD or the core LPS synthesis pathway may provide alternative therapeutic regimens for EHEC infection.

原文English
文章編號82
期刊Frontiers in Cellular and Infection Microbiology
6
發行號AUG
DOIs
出版狀態Published - 2016 八月 12

指紋

Enterohemorrhagic Escherichia coli
Innate Immunity
Lipopolysaccharides
Mutation
Enzymes
Escherichia coli Infections
Caenorhabditis elegans
Escherichia coli O157
Glycolipids
Gram-Negative Bacteria
Intestines
Immunity

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

引用此文

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title = "Mutation of the enterohemorrhagic escherichia coli core LPS biosynthesis enzyme RfaD confers hypersusceptibility to host intestinal innate immunity in vivo",
abstract = "Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important foodborne pathogen causing severe diseases in humans worldwide. Currently, there is no specific treatment available for EHEC infection and the use of conventional antibiotics is contraindicated. Therefore, identification of potential therapeutic targets and development of effective measures to control and treat EHEC infection are needed. Lipopolysaccharides (LPS) are surface glycolipids found on the outer membrane of gram-negative bacteria, including EHEC, and LPS biosynthesis has long been considered as potential anti-bacterial target. Here, we demonstrated that the EHEC rfaD gene that functions in the biosynthesis of the LPS inner core is required for the intestinal colonization and pathogenesis of EHEC in vivo. Disruption of the EHEC rfaD confers attenuated toxicity in Caenorhabditis elegans and less bacterial colonization in the intestine of C. elegans and mouse. Moreover, rfaD is also involved in the control of susceptibility of EHEC to antimicrobial peptides and host intestinal immunity. It is worth noting that rfaD mutation did not interfere with the growth kinetics when compared to the wild-type EHEC cells. Taken together, we demonstrated that mutations of the EHEC rfaD confer hypersusceptibility to host intestinal innate immunity in vivo, and suggested that targeting the RfaD or the core LPS synthesis pathway may provide alternative therapeutic regimens for EHEC infection.",
author = "Kuo, {Cheng Ju} and Chen, {Jenn Wei} and Chiu, {Hao Chieh} and Teng, {Ching Hao} and Hsu, {Tai I.} and Lu, {Pei Jung} and Syu, {Wan Jr} and Wang, {Sin Tian} and Chou, {Ting Chen} and Chen, {Chang Shi}",
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AU - Kuo, Cheng Ju

AU - Chen, Jenn Wei

AU - Chiu, Hao Chieh

AU - Teng, Ching Hao

AU - Hsu, Tai I.

AU - Lu, Pei Jung

AU - Syu, Wan Jr

AU - Wang, Sin Tian

AU - Chou, Ting Chen

AU - Chen, Chang Shi

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AB - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important foodborne pathogen causing severe diseases in humans worldwide. Currently, there is no specific treatment available for EHEC infection and the use of conventional antibiotics is contraindicated. Therefore, identification of potential therapeutic targets and development of effective measures to control and treat EHEC infection are needed. Lipopolysaccharides (LPS) are surface glycolipids found on the outer membrane of gram-negative bacteria, including EHEC, and LPS biosynthesis has long been considered as potential anti-bacterial target. Here, we demonstrated that the EHEC rfaD gene that functions in the biosynthesis of the LPS inner core is required for the intestinal colonization and pathogenesis of EHEC in vivo. Disruption of the EHEC rfaD confers attenuated toxicity in Caenorhabditis elegans and less bacterial colonization in the intestine of C. elegans and mouse. Moreover, rfaD is also involved in the control of susceptibility of EHEC to antimicrobial peptides and host intestinal immunity. It is worth noting that rfaD mutation did not interfere with the growth kinetics when compared to the wild-type EHEC cells. Taken together, we demonstrated that mutations of the EHEC rfaD confer hypersusceptibility to host intestinal innate immunity in vivo, and suggested that targeting the RfaD or the core LPS synthesis pathway may provide alternative therapeutic regimens for EHEC infection.

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