Mechanisms of pathogenesis for Enterococcus
My research laboratory is interested in understanding the mechanisms of pathogenesis for the opportunistic bacterial pathogen, Enterococcus faecalis. This organism now ranks as a leading cause of hospital acquired infection, causing a variety of infections ranging from urinary tract infection, bacteremia and wound infection to life threatening endocarditis. These infections are often difficult to treat due to the presence of multiple antibiotic resistances. One of the virulence properties of the organism of interest is the production of capsular polysaccharide. The presence of the capsule enhances the organism’s ability to persist in the host at sites of infection. The capsule is considered to be anti-phagocytic allowing the bacterium to escape killing by neutrophils in the absence of capsule specific antibodies. We are interested in determining the underlying genetic pathways related to the regulation and production of capsule, with the goal of identifying candidate targets for the development of new anti-infectives. We are also examining biofilm formation by this organism to determine those factors essential to this developmental process. Biofilms are aggregates of bacteria attached to a solid surface and are thought to be the primary mode of growth during infection. Understanding the basis for biofilm formation will allow us to target those key factors with the goal of disrupting a process vital to the organism’s ability to cause disease.
- Varahan S, Iyer VS, Moore WT, Hancock LE#. 2013. Eep confers lysozyme resistance to Enterococcus faecalis via the activation of the extracytoplasmic function sigma factor, SigV. J. Bacteriol. 195(14): 3125-34. Epub 2013 May 3.
- Teixeira N, Varahan S, Gorman MJ, Palmer KL, Zaidman-Remy A, Yokohata R, Nakayama J, Hancock LE, Jacinto A, Gilmore MS, Lopes MFS. 2013. Drosophila host model reveals new Enterococcus faecalis quorum-sensing associated virulence factors. PLoS One May 29;8(5):e64
- Teixeira N, Santos S, Marujo P, Yokohata R, Iyer VS, Nakayama J, Hancock LE, Serror P, Lopes MFS#. 2012. The incongruent gelatinase genotype and phenotype in Enterococcus faecalis are due to shutting off the ability to respond to the gelatinase biosynthesis-activating pheromone (GBAP) quorum-sensing signal. Microbiol. 158(Pt 2):519-28. Epub 2011 Nov 24.
- Iyer VS, Hancock LE#. 2012. Deletion of Sigma54 (rpoN) alters the rate of autolysis and biofilm formation in Enterococcus faecalis. J. Bacteriol. 194(2):368-75. Epub 2011 Nov 11
- Srivastava M, Mallard C, Barke T, Hancock LE, Self WT. 2011. A selenium-dependent xanthine dehydrogenase triggers biofilm proliferation in Enterococcus faecalis through oxidant production. J. Bacteriol. 193(7):1643-52. Epub 2011 Jan 21.
- Thurlow LR, Thomas VC, Narayanan S, Olson S, Fleming SD, Hancock LE#. 2010. Gelatinase contributes to the pathogenesis of endocarditis caused by Enterococcus faecalis. Infect Immun. 78(11):4936-43. Epub 2010 Aug 16.
- Manson JM, Hancock LE, and MS Gilmore#. 2010. Mechanism of chromosomal transfer of Enterococcus faecalis pathogenicity island, capsule, antimicrobial-resistance and other traits. Proc Natl Acad Sci U S A. 107(27):12269-74. Epub 2010 Jun 21.
- Guiton PS, Hung CS, Hancock LE, Caparon MG, Hultgren SJ#. 2010. Enterococcal biofilm formation and virulence in an optimized murine model of foreign body-associated urinary tract infections. Infect. Immun. 78(10):4166-75. Epub 2010 Aug 9.
- Macovei L, Ghosh A, Thomas VC, Hancock LE, Mahmood S, and Zurek L.# 2009. Enterococcus faecalis with the gelatinase phenotype regulated by the fsr operon and with biofilm-forming capacity are common in the agricultural environment. Environ. Microbiol. 11(6): 1540–1547.
- Thomas VC, Hiromasa Y, Harms N, Thurlow L, Tomich J, Hancock LE#. 2009. A fratricidal mechanism is responsible for eDNA release and biofilm development of Enterococcus faecalis. Mol. Microbiol. 72(4):1022-36. This paper was featured in the Research Highlights section of Nature Reviews Microbiology June 2009 vol. 7 no. 6, pg. 403.
- Thurlow LR, Thomas VC, Hancock LE#. 2009. Capsular polysaccharide production in Enterococcus faecalis and the contribution of CpsF to capsule serospecificity. J. Bacteriol. 191(20):6203-10. Epub 2009 Aug 14.
- Thomas VC, Hancock LE#. 2009. Suicide and fratricide in bacterial biofilms. Int J Artif Organs. 32(9):537-442.
- Thurlow LR, Thomas VC, Fleming SD, Hancock LE#. 2009. Enterococcus faecalis capsular polysaccharide serotypes C and D and their contributions to host innate immune evasion. Infect Immun. 77(12):5551-7 Epub 2009 Oct 5.
- Thomas VC, Thurlow LR, Boyle D, Hancock LE#. 2008. Regulation of autolysis-dependent eDNA release by Enterococcus faecalis extracellular proteases influences biofilm development. J. Bacteriol. 2008 Aug;190(16):5690-8. Epub 2008 Jun 13.