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Virginia L. Clark, Ph.D.

Contact

Call Center (585) 276-3000

About Me

Faculty Appointments

Professor Emeritus - Department of Microbiology and Immunology (SMD)

Credentials

Education

PhD | Univ Rochester Sch Med/Dent. Microbiology. 1977

BA | Carleton College. Chemistry. 1967

Research

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 of...
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 denitrification pathway in gonococcal virulence. We have elucidated the regulatory pathway for aniA and have identified the regulator of norB. Regulation of these two genes is complex, involving 2 activators and 3 repressors of transcription. We are currently working to identify the anaerobic regulon and the function of anaerobically regulated genes.

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. Thus. NO metabolism may enable gonococci to alter the host immune response. NO and its relative peroxynitrite are reactive nitrogen species that are toxic to many bacteria. We have determined that gonococci are highly resistant to the toxic effects of both of these compounds. We are currently working to identify the mechanism of peroxynitrite resistance in N. gonorrhoeae.

Publications

Journal Articles

The role of catalase in gonococcal resistance to peroxynitrite.

Spence SA, Clark VL, Isabella VM

Microbiology.. 2012 February 158 (Pt 2):560-570. Epub 11/24/2011.

Identification of a conserved protein involved in anaerobic unsaturated fatty acid synthesis in Neiserria gonorrhoeae: implications for facultative and obligate anaerobes that lack FabA.

Isabella VM, Clark VL

Molecular microbiology.. 2011 October 82 (2):489-501. Epub 09/19/2011.

Deep sequencing-based analysis of the anaerobic stimulon in Neisseria gonorrhoeae.

Isabella VM, Clark VL

BMC genomics.. 2011 January 2012 :51. Epub 01/20/2011.

Resistance to peroxynitrite in Neisseria gonorrhoeae.

Barth KR, Isabella VM, Wright LF, Clark VL

Microbiology.. 2009 August 155 (Pt 8):2532-2545. Epub 04/30/2009.

Functional analysis of NsrR, a nitric oxide-sensing Rrf2 repressor in Neisseria gonorrhoeae.

Isabella VM, Lapek JD, Kennedy EM, Clark VL

Molecular microbiology.. 2009 January 71 (1):227-39. Epub 1900 01 01.

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.

Barth K, Clark VL

Canadian journal of microbiology.. 2008 August 54 (8):639-46. Epub 1900 01 01.

Laboratory maintenance of Neisseria gonorrhoeae.

Spence JM, Wright L, Clark VL

Current protocols in microbiology.. 2008 February Chapter 4 :Unit 4A.1. Epub 1900 01 01.

cis- and trans-acting elements involved in regulation of norB (norZ), the gene encoding nitric oxide reductase in Neisseria gonorrhoeae.

Isabella V, Wright LF, Barth K, Spence JM, Grogan S, Genco CA, Clark VL

Microbiology.. 2008 January 154 (Pt 1):226-239. Epub 1900 01 01.

Role of ribosomal protein L12 in gonococcal invasion of Hec1B cells.

Spence JM, Clark VL

Infection and immunity.. 2000 September 68 (9):5002-10. Epub 1900 01 01.

Gonococcal nitric oxide reductase is encoded by a single gene, norB, which is required for anaerobic growth and is induced by nitric oxide.

Householder TC, Fozo EM, Cardinale JA, Clark VL

Infection and immunity.. 2000 September 68 (9):5241-6. Epub 1900 01 01.

Expression of AniA, the major anaerobically induced outer membrane protein of Neisseria gonorrhoeae, provides protection against killing by normal human sera.

Cardinale JA, Clark VL

Infection and immunity.. 2000 July 68 (7):4368-9. Epub 1900 01 01.

cis- and trans-acting elements involved in regulation of aniA, the gene encoding the major anaerobically induced outer membrane protein in Neisseria gonorrhoeae.

Householder TC, Belli WA, Lissenden S, Cole JA, Clark VL

Journal of bacteriology.. 1999 January 181 (2):541-51. Epub 1900 01 01.

A proposed role for the lutropin receptor in contact-inducible gonococcal invasion of Hec1B cells.

Spence JM, Chen JC, Clark VL

Infection and immunity.. 1997 September 65 (9):3736-42. Epub 1900 01 01.

Construction of a translational lacZ fusion system to study gene regulation in Neisseria gonorrhoeae.

Silver LE, Clark VL

Gene.. 1995 December 1166 (1):101-4. Epub 1900 01 01.

Revised sequence of the Porphyromonas gingivalis prtT cysteine protease/hemagglutinin gene: homology with streptococcal pyrogenic exotoxin B/streptococcal proteinase.

Madden TE, Clark VL, Kuramitsu HK

Infection and immunity.. 1995 January 63 (1):238-47. Epub 1900 01 01.

Expression of Porphyromonas gingivalis proteolytic activity in Escherichia coli.

Madden TE, Thompson TM, Clark VL

Oral microbiology and immunology.. 1992 December 7 (6):349-56. Epub 1900 01 01.

Isolation and nucleotide sequence of the gene (aniA) encoding the major anaerobically induced outer membrane protein of Neisseria gonorrhoeae.

Hoehn GT, Clark VL

Infection and immunity.. 1992 November 60 (11):4695-703. Epub 1900 01 01.

The major anaerobically induced outer membrane protein of Neisseria gonorrhoeae, Pan 1, is a lipoprotein.

Hoehn GT, Clark VL

Infection and immunity.. 1992 November 60 (11):4704-8. Epub 1900 01 01.

Enhancement of the invasive ability of Neisseria gonorrhoeae by contact with HecIB, an adenocarcinoma endometrial cell line.

Chen JC, Bavoil P, Clark VL

Molecular microbiology.. 1991 June 5 (6):1531-8. Epub 1900 01 01.

Distribution of a protein antigenically related to the major anaerobically induced gonococcal outer membrane protein among other Neisseria species.

Hoehn GT, Clark VL

Infection and immunity.. 1990 December 58 (12):3929-33. Epub 1900 01 01.

The RNA polymerases of Porphyromonas gingivalis and Fusobacterium nucleatum are unrelated to the RNA polymerase of Escherichia coli.

Klimpel KW, Clark VL

Journal of dental research.. 1990 September 69 (9):1567-72. Epub 1900 01 01.

Distribution of gonococcal lipopolysaccharide biosynthesis genes among strains of Neisseria gonorrhoeae and other neisserial species.

Palermo-Dilts DA, Silver LE, Clark VL

Microbial pathogenesis.. 1990 March 8 (3):227-33. Epub 1900 01 01.

Identification of subunits of gonococcal RNA polymerase by immunoblot analysis: evidence for multiple sigma factors.

Klimpel KW, Lesley SA, Clark VL

Journal of bacteriology.. 1989 July 171 (7):3713-8. Epub 1900 01 01.

Genetic loci and linkage associations in Neisseria gonorrhoeae and Neisseria meningitidis.

West SE, Clark VL

Clinical microbiology reviews.. 1989 April 2 Suppl (Suppl):S92-103. Epub 1900 01 01.

The heat shock response of type 1 and type 4 gonococci.

Klimpel KW, Clark VL

Sexually transmitted diseases.. 1989 16 (3):141-7. Epub 1900 01 01.

Transfer of a gonococcal beta-lactamase plasmid to conjugation-deficient Neisseria cinerea strains by transformation.

Genco CA, Clark VL

Journal of general microbiology.. 1988 December 134 (12):3277-83. Epub 1900 01 01.

Role of outer-membrane proteins and lipopolysaccharide in conjugation between Neisseria gonorrhoeae and Neisseria cinerea.

Genco CA, Clark VL

Journal of general microbiology.. 1988 December 134 (12):3285-94. Epub 1900 01 01.

Presence of antibodies to the major anaerobically induced gonococcal outer membrane protein in sera from patients with gonococcal infections.

Clark VL, Knapp JS, Thompson S, Klimpel KW

Microbial pathogenesis.. 1988 November 5 (5):381-90. Epub 1900 01 01.

Multiple protein differences exist between Neisseria gonorrhoeae type 1 and type 4.

Klimpel KW, Clark VL

Infection and immunity.. 1988 April 56 (4):808-14. Epub 1900 01 01.

Expression of a cloned lipopolysaccharide antigen from Neisseria gonorrhoeae on the surface of Escherichia coli K-12.

Palermo DA, Evans TM, Clark VL

Infection and immunity.. 1987 November 55 (11):2844-9. Epub 1900 01 01.