Professor & Vice Chair

Basic Sciences
Division of Microbiology
School of Medicine
Loma Linda University
Loma Linda, CA 92350
U.S.A

Phone:(909) 558- 8497
Fax:(909) 558-4035
E-mail: hfletcher@llu.edu

Profile Photo

Research Interest

It appears that only a few Gram-negative anaerobic bacteria, among the more than 700 microbial species known to exist in the human mouth, are associated with periodontal diseases.  In addition, some of these organisms are also associated with cardiovascular and other systemic diseases.  Porphyromonas gingivalis, a black-pigmented, gram-negative anaerobe, is an important etiological agent of periodontal disease and is also linked to cardiovascular disease. It produces several virulence factors (e.g., capsule, adhesin, membrane vesicles, and hydrolytic enzymes) that can contribute to its pathogenicity.  The overall objective of our research program is to elucidate the molecular mechanism(s) for virulence regulation in P. gingivalis and examine the effects of these virulence factors on the host-microbe interaction.  Our current research efforts are the following:  (1) Studies on the mechanisms of virulence regulation in P. gingivalis.  (2) Mechanisms for adaptation to oxidative stress in P. gingivalis.  (3) P. gingivalis - host interaction: gingipain-induced apoptosis. (4)  Mechanisms of nitric oxide stress resistance in P. gingivalis.  (5)  Studies on the role of sialidases in P. gingivalis pathogenesis.  (6)  Involvement of extracytoplasmic function sigma factors in virulence regulation in P. gingivalis.

Selected Publications

  1. McKenzie, R.M.E., N. A. Johnson, W. Aruni and H. M. Fletcher. 2010. The bcp gene in the bcp-recA-vimA-vimE-vimF operon is important in oxidative stress resistance in Porphyromonas gingivalis W83. Mol Oral Microbiol. In Press.
  2. Dou, Y., D. O. Osbourne, R. McKenzie, and H. M. Fletcher. 2010.  Involvement of extracytoplasmic function sigma factor in virulence regulation in Porphyromonas gingivalis W83. FEMS Microbiol. Lett. In Press.
  3. Vanterpool, E, A.W. Aruni, F. Roy, and H.M. Fletcher.  2010. regT can modulate gingipain activity and response to oxidative stress in Porphyromonas gingivalis.  Microbiology. 156:3065-72.
  4. Osbourne, D. O., W. Aruni, F. Roy, C. Perry, L. Sandberg, A. Muthiah And H. M. Fletcher. 2010.  The role of vimA in cell surface biogenesis in Porphyromonas gingivalis.  Microbiology. Microbiology. 156:2180-93.
  5. Henry, L, L. Sandberg, K. Zhang and H. M. Fletcher.  2008. DNA repair of 8-oxo-7,8-dihydroguanine lesions in Porphyromonas gingivalis..  J. Bacteriol. 190:7985-93. 
  6. S. M. Sheets, A. Robles-Price, R. M. E. Mckenzie, C. A. Casiano, and H. M. Fletcher. 2008. Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis. Frontiers in Bioscience. 13:3215-3238.
  7. Roy F., E. Vanterpool and H. M. Fletcher. 2006.  HtrA of Porphyromonas gingivalis can regulate growth and gingipain activity under stressful environmental conditions. Microbiology. 152:3391-3398.
  8. Vanterpool, E., F. Roy, S.M. Sheets, L. Sandberg and H. M. Fletcher.  2006. VimA is part of the maturation pathway for the major gingipains of P. gingivalis W83. Microbiology. 152:3383-3389.
  9. Sheets, S. M., Potempa, J., Travis, J. and  H. M. Fletcher and  C. A. Casiano.  2006. Gingipains from Porphyromonas gingivalis W83 synergistically disrupt endothelial cell adhesion and can induce caspase-independent apoptosis.  Infect. Immu.  74:5667-5678.
  10. Y. Asai, M. Hashimoto, H. M. Fletcher, K. Miyake, S. Akira T. Ogawa. 2005. Lipopolysaccharide Preparation Extracted from Porphyromonas gingivalis Lipoprotein-Deficient Mutant Shows a Marked Decrease in Toll-Like Receptor 2-Mediated Signaling.  Infect. Immu. 73: 2157-2163.
  11. Vanterpool, E, F. Roy and H.M. Fletcher. 2005.  Inactivation of vimF, a putative glycosyl transferase gene, which is downstream of vimE, alters the glycosylation and activation of the gingipains in Porphyromonas gingivalis W83 . Infect. Immu. 73: 3971-3982.
  12. Vanterpool, E, F. Roy and H.M. Fletcher. 2005. Altered gingipain maturation in the vimA and vimE-defective isogenic mutants of Porphyromonas gingivalis. Infect. Immu. 73: 1357-1366.
  13. Sheets, S. M., J. Potempa, J. Travis, C. A. Casiano and  H. M. Fletcher.  2005. Porphyromonas gingivalis  protease-induce cadherin proteolysis, loss of cell adhesion, and apoptosis in endothelial cells.  Infect. Immu. 73: 1543-1552.