URMC Microbiology Faculty: Virginia Clark

Faculty Profile

Ph.D. (1976)
Rochester

Virginia Clark
Associate Professor of Microbiology & Immunology
and of Oral Biology

Primary Appointment:
Microbiology & Immunology

Graduate Degree Programs
Immunology, Microbiology, and Virology - IMV

Contact Information

University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 672
Rochester, New York 14642

Medical Center 2-3019
Phone: (585) 275-3154
E-Mail: ginny_clark@urmc.rochester.edu

Research Focus: Regulation of Virulence Factors in Neisseria Gonorrhoeae
Research Overview: Neisseria gonorrhoeae (GC) is the etiologic agent of gonorrhea, still one of the most prevalent infectious diseases in the U.S. Untreated infections in women can lead to pelvic inflammatory disease (PID), a significant cause of infertility in this country. N. gonorrhoeae is often isolated along with obligate anaerobes, which presents a conundrum, as the gonococcus has been considered to be an obligate aerobe. We demonstrated that GC is actually a facultative anaerobic that can utilize nitrite as a terminal electron acceptor. An examination of genes that are only expressed anaerobically may reveal new virulence factors that are important in gonococcal pathogenesis.; N. gonorrhoeae grows anaerobically by using the central two reactions of the denitrification pathway, reduction of nitrite by AniA and reduction of nitric oxide by NorB. The gonococcus does not produce energy from these two reactions, but the pathway does enable the organism to maintain an oxidation/reduction balance anaerobically. The presence of AniA and NorB allows the gonococcus to produce and degrade nitric oxide (NO), known to be an important modulator of the host innate immune system and signal transduction pathways. This ability to keep NO at a low level may be responsible for the fact that most gonococcal infections in women are asymptomatic.; We are using a combination of genetic, physiologic, and cell biology techniques to better understand the role of the dentrification pathway in gonococcal virulence. We have elucidated the regulatory pathway for aniA and have identified the regulator of norB. We are also working to identify the anaerobic regulon using microarrays. We have determined that gonococci establish a NO steady state in the presence of a long half-lived NO donor, reducing the NO level from a pro-inflammatory concentration to an anti-inflammatory concentration. We are currently investigating whether gonococcal NO metabolism alters cytokine induction.; N. gonorrhoeae is an obligate human pathogen and there is no animal model system that reproduces human infection and disease. We have been using the invasion of the human endometrial cell line, Hec1B, as a model for gonococcal PID. We have found that gonococci increase their invasive ability when they come in contact with Hec1B cells, and that both induction of invasion and entry requires the presence of the lutropin receptor (LHr). We have demonstrated that surface-localized ribosomal protein L7/L12 has an integral role in LHr-mediated gonococcal invasion and that L7/L12 can bind directly to LHr..
Recent Publications: Isabella VM, Lapek Jr JD, Kennedy EM, Clark VL Functional analysis of NsrR, a nitric oxide-sensing Rrf2 repressor in Neisseria gonorrhoeae. Mol Microbiol. 2008 Nov 5;

Barth K, Clark VL Differences in nitric oxide steady states between arginine, hypoxanthine, uracil auxotrophs (AHU) and non-AHU strains of Neisseria gonorrhoeae during anaerobic respiration in the presence of nitrite. Can J Microbiol. 2008 Aug;54(8):639-46; Spence JM, Wright L, Clark VL Laboratory Maintenance of Neisseria gonorrhoeae. Curr Protoc Microbiol. 2008 Feb;Chapter 4:Unit4A.1; Isabella V, Wright LF, Barth K, Spence JM, Grogan S, Genco CA, Clark VL "cis- and trans-acting elements involved in regulation of norB (norZ), the gene encoding nitric oxide reductase in Neisseria gonorrhoeae." Microbiology. 2008 Jan;154(Pt 1):226-39; Cardinale JA, Clark VL. "Determinants of nitric oxide steady-state levels during anaerobic respiration by Neisseria gonorrhoeae." Mol Microbiol. 2005 Oct;58(1):177-88.; Spence JM, Tyler RE, Domaoal RA, Clark VL. "L12 enhances gonococcal transcytosis of polarized Hec1B cells via the lutropin receptor." Microb Pathog. 32:117-25, 2002.; Lissenden S, Mohan S, et al. "Identification of transcription activators that regulate gonococcal adaptation from aerobic to anaerobic or oxygen-limited growth." Mol Microbiol. 37:839-55, 2000.; Householder TC, Fozo EM, Cardinale JA, Clark VL. "Gonococcal nitric oxide reductase is encoded by a single gene, norB, which Is required for anaerobic growth and Is induced by nitric oxide." Infect Immun. 68:5241-6, 2000.; Spence JM, Clark VL. "Role of ribosomal protein L12 in gonococcal invasion of Hec1B cells." Infect Immun. 68:5002-10, 2000.; Cardinale JA, Clark VL. "Expression of AniA, the major anaerobically induced outer membrane protein of Neisseria gonorrhoeae, provides protection against killing by normal human sera." Infect Immun. 68:4368-9, 2000.; Householder TC, Belli WA, Lissenden S, Cole JA, Clark VL. "cis- and trans-acting elements involved in regulation of aniA, the gene encoding the major anaerobically induced outer membrane protein in Neisseria gonorrhoeae." J Bacteriol 181:541-51, 1999.