Division of Allergy and Infectious Diseases



Faculty




Totten, Patricia, Ph.D.
Research Associate Professor of Medicine, 


CONTACT INFORMATION
Box 359779
University of Washington
Seattle, Washington 98195

Phone: (206) 341-5350
Fax: (206) 341-5363
e-mail:  patotten@u.washington.edu 

LINK TO PAT TOTTEN'S COMMUNITY OF SCIENCE WEB PAGE


CURRENT INTERESTS

My research interests include (1) defining the molecular pathogenesis of chancroid, a genital ulcer disease caused by Haemophilus ducreyi, and (2) assessing the association of novel organisms, including Mycoplasma genitalium, with idiopathic STD syndromes. My research group has identified several potential virulence factors produced by Haemophilus ducreyi and is currently investigating their interactions with host cells in vitro and disease progression in our primate model for chancroid. We have identified a novel cell-associated cytolysin produced by all 90 strains of H. ducreyi tested, and have shown that this hemolysin is also expressed in vivo. This cytoysin, identified by its hemolytic phenotype, has a cell range that includes epithelial and inflammatory cell types, suggesting that it may be involved in the generation of tissue necrosis typical of genital ulcers and in inhibition of the immune response and clearance of this organism. We are currently testing these hypotheses using wild-type and genetically engineered cytolysin deficient strains of H. ducreyi in our primate model and analyzing disease progression, survival of the organism, and the strength of the immune response generated by infection. Recently, we have shown that H. ducreyi produces an activity that prevents the opsonic uptake of secondary targets by macrophages as well as preventing phagocytic killing of E. coli by this cell type. We are currently pursuing the molecular basis of this intriguing antiphagocytic phenotype.

Another research interest of my research group is the identification and association of fastidious, or even uncultivable organisms, with idiopathic STD disease syndromes. Thus, we used a case-control study to assess the association of several potential genital pathogens with nongonoccocal urethritis and showed an association of M. genitalium with this STD syndrome. In the following years, we expanded these findings by showing as association of M. genitalium with cervicitis and with endometritis, disease syndromes that may have important sequelae in women. We plan to pursue these exciting findings by determining the natural history of M. genitalium infection, by identifying risk factors and risk markers for infection, and by assessing the association of this organism with these and other reproductive tract disease syndromes in women. Finally, we are currently using rDNA PCR followed by DNA sequencing to identify organisms infecting the fallopian tubes among women with salpingitis and have discovered novel organisms not detected in our controls. We plan to develop specific PCR assays to detect these organisms in larger sample sets and assess their association with reproductive tract disease syndromes in women.

PUBLICATIONS

Manhart LE, Critchlow CW, Holmes KK, Dutro SM, Eschenbach DA, Stevens CE, Totten PA. Mucopurulent cervicitis and Mycoplasma genitalium. J Infect Dis 187:650-7, 2003.

Cohen CR, Manhart LE, Bukusi EA, Astet S, Brunham RC, Holmes KK, Sinei SK, Bwayo JJ, Totten PA. Association between Mycoplasma genitalium and acute endometritis. Lancet 359:765-6, 2002.

Totten PA, Schwartz MA, Sjöström KE, Kenny GE, Handsfield HH, Weiss JB, Whittington WH. Association of Mycoplasma genitalium with nongonococcal urethritis in heterosexual men. J Infect Dis 183:269-76, 2001.

Wood GE, Dutro SM, Totten PA. Haemophilus ducreyi inhibits phagocytosis by U-937 cells, a human macrophage-like cell line. Infect Immun 69:4726-33, 2001.

Wood GE, Dutro SM, Totten PA. Target cell range of the Haemophilus ducreyi hemolysin and its involvement in invasion of human epithelial cells. Infect Immun 67:3740-9, 1999.



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