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Journal of Bacteriology, August 2009, p. 4758-4766, Vol. 191, No. 15
0021-9193/09/$08.00+0     doi:10.1128/JB.00489-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Single Substitution I259T, Conserved in the Plasminogen Activator Pla of Pandemic Yersinia pestis Branches, Enhances Fibrinolytic Activity {triangledown}

Johanna Haiko,1 Maini Kukkonen,1 Janne J. Ravantti,2 Benita Westerlund-Wikström,1 and Timo K. Korhonen1*

General Microbiology, Faculty of Biosciences, FI-00014 University of Helsinki, Finland,1 Institute of Biotechnology, Faculty of Biosciences, FI-00014 University of Helsinki, Finland2

Received 9 April 2009/ Accepted 13 May 2009

The outer membrane plasminogen activator Pla of Yersinia pestis is a central virulence factor in plague. The primary structure of the Pla β-barrel is conserved in Y. pestis biovars Antiqua, Medievalis, and Orientalis, which are associated with pandemics of plague. The Pla molecule of the ancestral Y. pestis lineages Microtus and Angola carries the single amino acid change T259I located in surface loop 5 of the β-barrel. Recombinant Y. pestis KIM D34 or Escherichia coli XL1 expressing Pla T259I was impaired in fibrinolysis and in plasminogen activation. Lack of detectable generation of the catalytic light chain of plasmin and inactivation of plasmin enzymatic activity by the Pla T259I construct indicated that Microtus Pla cleaved the plasminogen molecule more unspecifically than did common Pla. The isoform pattern of the Pla T259I molecule was different from that of the common Pla molecule. Microtus Pla was more efficient than wild-type Pla in {alpha}2-antiplasmin inactivation. Pla of Y. pestis and PgtE of Salmonella enterica have evolved from the same omptin ancestor, and their comparison showed that PgtE was poor in plasminogen activation but exhibited efficient antiprotease inactivation. The substitution 259IIDKT/TIDKN in PgtE, constructed to mimic the L5 region in Pla, altered proteolysis in favor of plasmin formation, whereas the reverse substitution 259TIDKN/IIDKT in Pla altered proteolysis in favor of {alpha}2-antiplasmin inactivation. The results suggest that Microtus Pla represents an ancestral form of Pla that has evolved into a more efficient plasminogen activator in the pandemic Y. pestis lineages.

* Corresponding author. Mailing address: General Microbiology, Faculty of Biosciences, FI-00014 University of Helsinki, Finland. Phone: 358 9 1915 9260. Fax: 358 9 1915 8754. E-mail: timo.korhonen{at}helsinki.fi

{triangledown} Published ahead of print on 22 May 2009.

Journal of Bacteriology, August 2009, p. 4758-4766, Vol. 191, No. 15
0021-9193/09/$08.00+0     doi:10.1128/JB.00489-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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