Mutation of the enterohemorrhagic escherichia coli core LPS biosynthesis enzyme RfaD confers hypersusceptibility to host intestinal innate immunity in vivo
Journal
Frontiers in Cellular and Infection Microbiology
Journal Volume
6
Journal Issue
AUG
Date Issued
2016
Author(s)
Kuo C.-J.
Chen J.-W.
Teng C.-H.
Hsu T.-I.
Lu P.-J.
Syu W.-J.
Wang S.T.
Chou T.-C.
Chen C.-S.
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. ? 2016 Kuo, Chen, Chiu, Teng, Hsu, Lu, Syu, Wang, Chou and Chen.
Subjects
Antimicrobial peptides (AMPs); Caenorhabditis elegans; Enterohemorrhagic Escherichia coli (EHEC); Intestinal innate immunity; Lipopolysaccharide (LPS); RfaD/GmhD/WaaD
SDGs
Other Subjects
act 5 protein; colistin; lipopolysaccharide; membrane protein; polymyxin B; polypeptide antibiotic agent; rfaD gene encoding protein; unclassified drug; ACT-5 protein, C elegans; actin; ADP-L-glycero-D-mannoheptose-6-epimerase; antimicrobial cationic peptide; Caenorhabditis elegans protein; CAP18 lipopolysaccharide-binding protein; epimerase; Escherichia coli protein; hldD protein, E coli; lipopolysaccharide; virulence factor; adult; animal experiment; animal tissue; Article; bacterial colonization; Caenorhabditis elegans; colony forming unit; controlled study; enterohemorrhagic Escherichia coli; enzyme synthesis; Escherichia coli infection; female; gene; immunopathogenesis; infection sensitivity; innate immunity; minimum inhibitory concentration; mouse; mutation; nonhuman; phenotype; polyacrylamide gel electrophoresis; protein expression; protein isolation; rfaD gene; survival analysis; animal; biosynthesis; C57BL mouse; chemistry; disease model; enteropathy; enzymology; Escherichia coli Infections; Escherichia coli O157; gene deletion; genetics; human; immunology; innate immunity; intestine; metabolism; microbiology; pathology; Actins; Animals; Antimicrobial Cationic Peptides; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Carbohydrate Epimerases; Disease Models, Animal; Escherichia coli Infections; Escherichia coli O157; Escherichia coli Proteins; Female; Humans; Immunity, Innate; Intestinal Diseases; Intestines; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Sequence Deletion; Virulence Factors
Type
journal article