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Lack of O‐antigen is essential for plasminogen activation by Yersinia pestis and Salmonella enterica
Author(s) -
Kukkonen Maini,
Suomalainen Marjo,
Kyllönen Päivi,
Lähteenmäki Kaarina,
Lång Hannu,
Virkola Ritva,
Helander Ilkka M.,
Holst Otto,
Korhonen Timo K.
Publication year - 2004
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2003.03817.x
Subject(s) - yersinia pestis , biology , salmonella enterica , microbiology and biotechnology , bacterial outer membrane , lipid a , yersinia , antigen , yersinia pseudotuberculosis , enterobacteriaceae , plasminogen activator , lipopolysaccharide , bacterial adhesin , proteases , virulence , recombinant dna , escherichia coli , biochemistry , bacteria , immunology , enzyme , gene , genetics , endocrinology
Summary The O‐antigen of lipopolysaccharide (LPS) is a virulence factor in enterobacterial infections, and the advantage of its genetic loss in the lethal pathogen Yersinia pestis has remained unresolved. Y. pestis and Salmonella enterica express β‐barrel surface proteases of the omptin family that activate human plasminogen. Plasminogen activation is central in pathogenesis of plague but has not, however, been found to be important in diarrhoeal disease. We observed that the presence of O‐antigen repeats on wild‐type or recombinant S. enterica , Yersinia pseudotuberculosis or Escherichia coli prevents plasminogen activation by PgtE of S. enterica and Pla of Y. pestis ; the O‐antigen did not affect incorporation of the omptins into the bacterial outer membrane. Purified His 6 ‐Pla was successfully reconstituted with rough LPS but remained inactive after reconstitution with smooth LPS. Expression of smooth LPS prevented Pla‐mediated adhesion of recombinant E. coli to basement membrane as well as invasion into human endothelial cells. Similarly, the presence of an O‐antigen prevented PgtE‐mediated bacterial adhesion to basement membrane. Substitution of Arg‐138 and Arg‐171 of the motif for protein binding to lipid A 4′‐phosphate abolished proteolytic activity but not membrane translocation of PgtE, indicating dependence of omptin activity on a specific interaction with lipid A. The results suggest that Pla and PgtE require LPS for activity and that the O‐antigen sterically prevents recognition of large‐molecular‐weight substrates. Loss of O‐antigen facilitates Pla functions and invasiveness of Y. pestis ; on the other hand, smooth LPS renders plasminogen activator cryptic in S. enterica .