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The mammalian cell entry (Mce) protein of pathogenic Leptospira species is responsible for RGD motif-dependent infection of cells and animals
Molecular Microbiology
  • Lei Zhang, Zhejiang Provincial Center for Disease Control and Prevention
  • Chenglin Zhang
  • David M. Ojcius, University of the Pacific
  • Dexter Sun, Cornell University
  • Jinfang Zhao, Zhejiang University
  • Xu'ai Lin, Zhejiang University School of Medicine
  • Liwei Li
  • Lanjuan Li
  • Jie Yan, Zhejiang University School of Medicine
ORCiD
David M. Ojcius: 0000-0003-1461-4495
Document Type
Article
DOI
10.1111/j.1365-2958.2012.07985.x
Publication Date
3-1-2012
Abstract
Mammalian cell entry proteins (Mces) contribute to Mycobacterium tuberculosis virulence. A mce homologue has been identified in the Leptospira interrogans genome, but its function was unknown. We showed that the mce gene is expressed only by pathogenic Leptospira strains tested. Leptospiral mce mRNA and Mce protein levels increased during infection of macrophages. The ability to infect macrophages was significantly lower in a strain with the mce gene deleted (mce-). Complementation of the mce gene restored the ability of the mutant strain (mcecom) to adhere to and invade cells. Importantly, the mce gene knock-in strain (mce+) derived from L. biflexa acquired the ability to infect cells, and the mce+/ΔRAA knock-in strain (in which the RGD motif was replaced by RAA) was unable to infect cells. The mce- mutant was also dramatically less efficient in infecting hamsters than the wild-type L. interrogans strain, and fewer leptospires of the mutant were found in peripheral blood monocytes and the urine from infected animals. The recombinant Mce protein showed a high binding affinity to the integrins α5β1 and αVβ3. Blockade of the two integrins or the Mce protein decreased leptospiral adherence and invasiveness. The results showed that Mce is an RGD-motif-dependent virulence factor in pathogenic Leptospira species.
Citation Information
Lei Zhang, Chenglin Zhang, David M. Ojcius, Dexter Sun, et al.. "The mammalian cell entry (Mce) protein of pathogenic Leptospira species is responsible for RGD motif-dependent infection of cells and animals" Molecular Microbiology Vol. 83 Iss. 5 (2012) p. 1006 - 1023 ISSN: 0950-382X
Available at: http://works.bepress.com/david-ojcius/224/