Ken Fields , Ph.D.

Assistant Professor of Microbiology and Immunology
Room 3033 (office) / 3084 (lab), Rosenstiel Medical Sciences Building
1600 NW 10th Avenue
Office: 305-243-6711
Lab: 305-243-6118
Fax: 305-243-4623
kfields@med.miami.edu

Research Interests:

The Gram-negative bacterium Chlamydia trachomatis is an obligate intracellular, medically significant human pathogen capable of colonizing genital or ocular mucosal epithelia. Infections by genital-specific C. trachomatis serovars represent the most common reportable sexually transmitted disease in the United States with an average of 4 million new cases reported annually. Ocular-specific serovars potentially affect 400 million people worldwide. Infections result in progressive corneal scarring that can lead to trachoma, the most prevalent form of preventable blindness worldwide. Disease pathology most likely results from the significant inflammatory response provoked by chlamydial infection and not by specific toxins per se. Pathology is exacerbated and in some cases may depend on repeated or chronic infection. The fact that most chlamydial genital infections are asymptomatic until serious, irreversible pathology develops makes this a particularly insidious and costly pathogen. Significantly, infections fail to elicit solid, long-term protective immunity, and there is currently no efficacious vaccine available. Chlamydia e develop entirely within a parasitophorous vacuole termed an inclusion, which remains non-fusogenic with the host endocytic pathway. Although Chlamydiae certainly stimulate and are susceptible to inactivation by mediators of both cellular and humoral immunity, their ability to persist is likely related to an ability to exploit the privileged intracellular niche afforded by the inclusion. The focus of my lab is to understand how Chlamydia, while sequestered within a membrane-bound vacuole, are able to directly modulate host-cell functions and thereby create and maintain a pathogen-permissive environment. Specifically, the lab studies contributions of a type III secretion mechanism to chlamydial pathogenesis.

The type III mechanism has been described in a diverse array of medically and commercially significant bacterial pathogens (see pages of Drs. Greg Plano and Kurt Schesser) and represents a sophisticated secretion system used to deploy anti-host proteins termed effectors that disrupt the host’s ability to effectively combat infection. Type III systems are essential for full virulence, and although the secretory apparatus is somewhat conserved among pathogenic bacteria, the complement of effectors varies depending on the needs of the specific pathogen. Chlamydia genomes contain genes encoding a functional type III apparatus but consistent with Chlamydia’s unique niche, lack coding sequences for effectors homologous to recognized effectors in other systems. Since there is currently no tractable genetic system for Chlamydia, a screen for chlamydial type III effectors has been developed using the heterologous Yersinia type III system. The contributions of these effectors to chlamydial pathogenesis are the primary focus of the lab.

Current projects include:

• Identification of host targets for currently identified Chlamydia type III effectors.

• Study of the consequences of these interactions on chlamydial pathogenesis and development.

• Elucidation of additional Chlamydia effectors using the heterologous Yersinia type III system.

A secondary focus in the lab is the investigation of potentially host-interactive components of the type III apparatus.

Current projects include:

• Identification of surface-exposed components of the Chlamydia type III apparatus.

• Studies designed to identify direct interactions of apparatus components with host cells and evaluate functional consequences of those interactions.

• Assessment of surface-exposed type III components as targets for neutralizing antibodies.

Selected Publications:

Betts, H.J., Twiggs, L.E., Sal, M.S., Wyrick, P.B., and Fields, K.A.  2008.  Bioinformatic and biochemical evidence for the identification of the type III secretion system needle protein of Chlamydia trachomatis.  J. Bacteriol. 190:1680-1690. 

Chellas-Gery, B., Linton, C.N., and Fields, K.A. 2007.  Human GCIP interacts with CT847, a novel Chlamydia trachomatis type III secretion substrate, and is degraded in a tissue-culture infection model.  Cell Microbiol. 9:2417-2430.

Wolf, K., Betts, H.J., Chellas-Gery, B., Hower, S., Linton, C.N., and Fields K.A. 2006.  Treatment of Chlamydia trachomatis with a small molecule inhibitor of the Yersinia type III secretion system disrupts progression of the chlamydial developmental cycle. Mol Microbiol.  61:1543-1555.

Fields, K.A., Fischer, E.R., Mead, D.J., Hackstadt, T. 2005.  Analysis of putative
C. trachomatis chaperones Scc2 and Scc3 and their use in identification of type III secretion substrates.  J. Bacteriol.  187:6466-6478.

Clifton, D.R., Fields, K.A., Grieshaber, S.S., Dooley, C.A., Fischer, E.R., Mead, D.J., Carabeo, R.A., and Hackstadt, T. (2004) A chlamydial type III translocated protein is tyrosine-phosphorylated at the site of entry and associated with recruitment of actin. Proc Natl Acad Sci U S A 101: 10166-10171.