Yersinia pestis pFra Shows Biovar-Specific Differences and Recent Common Ancestry with aSalmonella enterica Serovar Typhi Plasmid

ABSTRACT Population genetic studies suggest that Yersinia pestis, the cause of plague, is a clonal pathogen that has recently emerged from Yersinia pseudotuberculosis. Plasmid acquisition is likely to have been a key element in this evolutionary leap from an enteric to a flea-transmitted systemic pathogen. However, the origin of Y. pestis-specific plasmids remains obscure. We demonstrate specific plasmid rearrangements in different Y. pestis strains which distinguish Y. pestis bv. Orientalis strains from other biovars. We also present evidence for plasmid-associated DNA exchange between Y. pestis and the exclusively human pathogen Salmonella enterica serovar Typhi.

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Complete Genome Assembly of Yersinia pseudotuberculosis IP2666pIB1

Microbiology Resource Announcements ◽

10.1128/mra.01592-18 ◽

2019 ◽

Vol 8 (7) ◽

Cited By ~ 1

Author(s):

Adam Zoubeidi ◽

Leah Schwiesow ◽

Victoria Auerbuch ◽

Hanh N. Lam

Keyword(s):

Yersinia Pestis ◽

Genome Assembly ◽

Complete Genome ◽

Yersinia Pseudotuberculosis ◽

Model Organism ◽

Genomic Analysis ◽

Bacterial Pathogenesis ◽

Bacterial Virulence ◽

Human Pathogen ◽

Content Type

Yersinia pseudotuberculosis, closely related to Yersinia pestis, is a human pathogen and model organism for studying bacterial pathogenesis. To aid in genomic analysis and understanding bacterial virulence, we sequenced and assembled the complete genome of the human pathogen Yersinia pseudotuberculosis IP2666pIB1.

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Molecular Recognition of Chymotrypsin by the Serine Protease Inhibitor Ecotin from Yersinia pestis

Journal of Biological Chemistry ◽

10.1074/jbc.m111.225730 ◽

2011 ◽

Vol 286 (27) ◽

pp. 24015-24022 ◽

Cited By ~ 10

Author(s):

Elizabeth A. Clark ◽

Nicola Walker ◽

Donna C. Ford ◽

Ian A. Cooper ◽

Petra C. F. Oyston ◽

...

Keyword(s):

Protease Inhibitor ◽

Yersinia Pestis ◽

Serine Protease ◽

Antimicrobial Therapy ◽

Yersinia Pseudotuberculosis ◽

Serine Protease Inhibitor ◽

Human Pathogen ◽

Biologically Relevant ◽

Bioinformatic Approach ◽

Broad Specificity

Resistance to antibiotics is a problem not only in terms of healthcare but also biodefense. Engineering of resistance into a human pathogen could create an untreatable biothreat pathogen. One such pathogen is Yersinia pestis, the causative agent of plague. Previously, we have used a bioinformatic approach to identify proteins that may be suitable targets for antimicrobial therapy and in particular for the treatment of plague. The serine protease inhibitor ecotin was identified as one such target. We have carried out mutational analyses in the closely related Yersinia pseudotuberculosis, validating that the ecotin gene is a virulence-associated gene in this bacterium. Y. pestis ecotin inhibits chymotrypsin. Here, we present the structure of ecotin in complex with chymotrypsin to 2.74 Å resolution. The structure features a biologically relevant tetramer whereby an ecotin dimer binds to two chymotrypsin molecules, similar to what was observed in related serine protease inhibitor structures. However, the vast majority of the interactions in the present structure are distinctive, indicating that the broad specificity of the inhibitor for these proteases is based largely on its capacity to recognize features unique to each of them. These findings will have implications for the development of small ecotin inhibitors for therapeutic use.

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The Omptins of Yersinia pestis and Salmonella enterica Cleave the Reactive Center Loop of Plasminogen Activator Inhibitor 1

Journal of Bacteriology ◽

10.1128/jb.00458-10 ◽

2010 ◽

Vol 192 (18) ◽

pp. 4553-4561 ◽

Cited By ~ 33

Author(s):

Johanna Haiko ◽

Liisa Laakkonen ◽

Katri Juuti ◽

Nisse Kalkkinen ◽

Timo K. Korhonen

Keyword(s):

Yersinia Pestis ◽

Plasminogen Activator ◽

Salmonella Enterica ◽

Yersinia Pseudotuberculosis ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

Reactive Center Loop ◽

Reactive Center ◽

Activator Inhibitor ◽

Pai 1

ABSTRACT Plasminogen activator inhibitor 1 (PAI-1) is a serine protease inhibitor (serpin) and a key molecule that regulates fibrinolysis by inactivating human plasminogen activators. Here we show that two important human pathogens, the plague bacterium Yersinia pestis and the enteropathogen Salmonella enterica serovar Typhimurium, inactivate PAI-1 by cleaving the R346-M347 bait peptide bond in the reactive center loop. No cleavage of PAI-1 was detected with Yersinia pseudotuberculosis, an oral/fecal pathogen from which Y. pestis has evolved, or with Escherichia coli. The cleavage and inactivation of PAI-1 were mediated by the outer membrane proteases plasminogen activator Pla of Y. pestis and PgtE protease of S. enterica, which belong to the omptin family of transmembrane endopeptidases identified in Gram-negative bacteria. Cleavage of PAI-1 was also detected with the omptins Epo of Erwinia pyrifoliae and Kop of Klebsiella pneumoniae, which both belong to the same omptin subfamily as Pla and PgtE, whereas no cleavage of PAI-1 was detected with omptins of Shigella flexneri or E. coli or the Yersinia chromosomal omptins, which belong to other omptin subfamilies. The results reveal a novel serpinolytic mechanism by which enterobacterial species expressing omptins of the Pla subfamily bypass normal control of host proteolysis.

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