Deletion of Lipoprotein PG0717 in Porphyromonas gingivalis W83 Reduces Gingipain Activity and Alters Trafficking in and Response by Host Cells

Leticia Reyes, Eileen Eiler-McManis, Paulo H. Rodrigues, Amandeep S. Chadda, Shannon M. Wallet, Myriam Bélanger, Amanda G. Barrett, Sophie Alvarez, Debra Akin, William A. Dunn, Ann Progulske-Fox

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14 Scopus citations

Abstract

P. gingivalis (Pg), a causative agent of chronic generalized periodontitis, has been implicated in promoting cardiovascular disease. Expression of lipoprotein gene PG0717 of Pg strain W83 was found to be transiently upregulated during invasion of human coronary artery endothelial cells (HCAEC), suggesting this protein may be involved in virulence. We characterized the virulence phenotype of a PG0717 deletion mutant of pg W83. There were no differences in the ability of W83Δ717 to adhere and invade HCAEC. However, the increased proportion of internalized W83 at 24 hours post-inoculation was not observed with W83Δ717. Deletion of PG0717 also impaired the ability of W83 to usurp the autophagic pathway in HCAEC and to induce autophagy in Saos-2 sarcoma cells. HCAEC infected with W83Δ717 also secreted significantly greater amounts of MCP-1, IL-8, IL-6, GM-CSF, and soluble ICAM-1, VCAM-1, and E-selectin when compared to W83. Further characterization of W83Δ717 revealed that neither capsule nor lipid A structure was affected by deletion of PG0717. Interestingly, the activity of both arginine (Rgp) and lysine (Kgp) gingipains was reduced in whole-cell extracts and culture supernatant of W83Δ717. RT-PCR revealed a corresponding decrease in transcription of rgpB but not rgpA or kgp. Quantitative proteome studies of the two strains revealed that both RgpA and RgpB, along with putative virulence factors peptidylarginine deiminase and Clp protease were significantly decreased in the W83Δ717. Our results suggest that PG0717 has pleiotropic effects on W83 that affect microbial induced manipulation of host responses important for microbial clearance and infection control.

Original languageEnglish (US)
Article numbere74230
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 12 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Reyes, L., Eiler-McManis, E., Rodrigues, P. H., Chadda, A. S., Wallet, S. M., Bélanger, M., Barrett, A. G., Alvarez, S., Akin, D., Dunn, W. A., & Progulske-Fox, A. (2013). Deletion of Lipoprotein PG0717 in Porphyromonas gingivalis W83 Reduces Gingipain Activity and Alters Trafficking in and Response by Host Cells. PloS one, 8(9), [e74230]. https://doi.org/10.1371/journal.pone.0074230