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Microbial Pathogenesis

The research interests of my laboratory are focused on genetic and biochemical analyses of Gram-positive bacterial pathogens. 

One focus of research is  the toxin producing bacterial species Corynebacterium diphtheriae. C. diphtheriae is a toxigenic human pathogene and a model organism for the study of metal-dependent gene regulation in Gram-positive and acid-fast bacterial species. The diphtheria toxin repressor DtxR is the primary iron-responsive transcriptional regulator in C. diphtheriae and regulators homologous to DtxR are found in many bacterial species (including the pathogenic Mycobacteria).  In addition we identified and described a zinc uptake regulator, Zur in C. diphtheraie.  We are investigating the role(s) of DtxR, Zur and other metal-dependent regulators in metal homeostasis, oxidative stress protection systems and pathogenesis.

We are also intertested in disecting the role that gene regulation in response to oxidative stress plays in pathogenesis.  To that end we are studing the regulators that control transcription in response to reactive oxygen species including the hydrogen peroxide responsive protein OxyR. 

Illuminating the mechanisms that protect C. diphtheriae from reactive oxygen species will  provide information on mechanisms used by C. diphtheriae to evade host defenses that rely on causing oxidative damage and may reveal new targets for the development of antimicrobial agents active against many Gram positive bacterial pathogens.

In addition to our work with C. diphtheriae we have expanded our focus to include metal and oxidative stress dependent gene regulation in the Gram positive nosicomial pathogen Enterococcus faecalis. Hospital acquired E. faecalis strains are often resistant to multiple antibiotics and in addition these strains serve as a reservoir of antibiotic resistance genes that can be transferred to other bacterial pathogens. New methods to treat and prevent infection by E. faecalis are sorely needed. E. faecalis encodes proteins with homology both to DtxR and Zur and little is currently known about the function of these proteins. Our goals are to characterize the role of these proteins in pathogenesis of and gene regulation in E. faecalis and thereby to provide new targets for the development of antimicrobials. 

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