title: Varying dependency of periplasmic peptidylprolyl cis-trans isomerases in promoting Yersinia pseudotuberculosis stress tolerance and pathogenicity.
abstract: Periplasmic PPIases (peptidylprolyl cis-trans isomerases) catalyse the cis-trans isomerization of peptidyl-prolyl bonds, which is a rate-limiting step during protein folding. We demonstrate that the surA, ppiA, ppiD, fkpA and fklB alleles each encode a periplasmic PPIase in the bacterial pathogen Yersinia pseudotuberculosis. Of these, four were purified to homogeneity. Purified SurA, FkpA and FklB, but not PpiD, displayed detectable PPIase activity in vitro. Significantly, only Y. pseudotuberculosis lacking surA caused drastic alterations to the outer membrane protein profile and FA (fatty acid) composition. They also exhibited aberrant cellular morphology, leaking LPS (lipopolysaccharide) into the extracellular environment. The SurA PPIase is therefore most critical for maintaining Y. pseudotuberculosis envelope integrity during routine culturing. On the other hand, bacteria lacking either surA or all of the genes ppiA, ppiD, fkpA and fklB were sensitive to hydrogen peroxide and were attenuated in mice infections. Thus Y. pseudotuberculosis exhibits both SurA-dependent and -independent requirements for periplasmic PPIase activity to ensure in vivo survival and a full virulence effect in a mammalian host.
authors: Department of Molecular Biology and Umeå Center for Microbial Research, Umeå University, SE-901 87 Umeå, Sweden.
authors: Ikenna R
authors: IR
authors: Obi
authors: Roland
authors: R
authors: Nordfelth
authors: Matthew S
authors: MS
authors: Francis
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019897:Periplasm / Q000201:enzymology*; D013347:Subcellular Fractions / Q000378:metabolism; D015011:Yersinia pseudotuberculosis / Q000201:enzymology / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; C098640:periplasmic peptidylprolyl cis-trans isomerase; D019696:Peptidylprolyl Isomerase