Open AccessVibrio cholerae ensures function of host proteins required for virulence through consumption of luminal methionine sulfoxide
Author(s) -
Audrey S. Vanhove,
Saiyu Hang,
Vidhya Vijayakumar,
Adam C. N. Wong,
John M. Asara,
Paula I. Watnick
Publication year - 2017
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1006428
Subject(s) - msra , vibrio cholerae , virulence , methionine sulfoxide reductase , biology , methionine , microbiology and biotechnology , enterocyte , biochemistry , bacteria , gene , amino acid , genetics , small intestine
Vibrio cholerae is a diarrheal pathogen that induces accumulation of lipid droplets in enterocytes, leading to lethal infection of the model host Drosophila melanogaster . Through untargeted lipidomics, we provide evidence that this process is the product of a host phospholipid degradation cascade that induces lipid droplet coalescence in enterocytes. This infection-induced cascade is inhibited by mutation of the V . cholerae glycine cleavage system due to intestinal accumulation of methionine sulfoxide (MetO), and both dietary supplementation with MetO and enterocyte knock-down of host methionine sulfoxide reductase A (MsrA) yield increased resistance to infection. MsrA converts both free and protein-associated MetO to methionine. These findings support a model in which dietary MetO competitively inhibits repair of host proteins by MsrA. Bacterial virulence strategies depend on functional host proteins. We propose a novel virulence paradigm in which an intestinal pathogen ensures the repair of host proteins essential for pathogenesis through consumption of dietary MetO.