Identification of novel substrates of Shigella T3SA through analysis of its virulence plasmid-encoded secretome

• DOI: 10.1371/journal.pone.0186920
• Publication Date: 2017-10-26T18:06:01Z
• Authors: Laurie Pinaud; Mariana L. Ferrari; Robin Friedman; Nico Jehmlich; Martin von Bergen; Armelle Phalipon; Philippe J. Sanso...; François-Xavier C...
• Keywords: Yersinia enterocolitica; Salmonella enterica; Enteropathogenic Escherichia coli; Antitoxin

Many human Gram-negative bacterial pathogens express a Type Three Secretion Apparatus (T3SA), including among the most notorious Shigella spp., Salmonella enterica, Yersinia enterocolitica and enteropathogenic Escherichia coli (EPEC). These bacteria on their surface multiple copies of T3SA that mediate delivery into host cells specific protein substrates critical to pathogenesis. spp. are responsible for bacillary dysentery. The effector function several has largely been studied but potential cellular targets far from having comprehensively delineated. In addition, it is likely some have escaped scrutiny as yet. Indeed, sequencing virulence plasmid flexneri revealed numerous open reading frames with unknown functions could encode additional substrates. Taking advantage label-free mass spectrometry detection proteins secreted by constitutively secreting strain S. flexneri, we identified five novel T3SA. We further confirmed secretion through translocation using β-lactamase assays. coding sequences two these (Orf13 Orf131a) guanine-cytosine content comparable those components effectors. three other (Orf48, Orf86 Orf176) significant homology antitoxin moieties type II Toxin-Antitoxin systems usually implicated in maintenance low copy plasmids. While Orf13 Orf131a might constitute new effectors contributing pathogenicity, roles antitoxins or antitoxin-like during infection discussed.