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Melissa Broadway

Advisor: Hung Ton-That, Ph.D.

Accepted position of Research and Development Associate at SpectraCell Laboratories, Inc after receiving PhD
Now is a Juris Doctor Candidate in Intellectual Property Law at The University of Houston Law Center

Corynebacterium diphtheriae is the causative agent of cutaneous and pharyngeal diphtheria in humans. The disease is manifested by bacterial colonization and production of diphtheria toxin. While lethality is certainly caused by this toxin, corynebacterial colonization may primarily require proteinaceous fibers called pili, which mediate adherence to specific tissues. The type strain of C. diphtheriae possesses three distinct pilus structures, namely the SpaA-, SpaD-, and SpaH-type pili, which are encoded by three distinct pilus gene clusters. Each pilus is composed of a major pilin forming the pilus shaft and two minor pilins, one of which is located at the tip region, the other at the pilus base. The pilus is assembled onto the bacterial peptidoglycan by a specific transpeptidase enzyme called sortase. Although the SpaA pili are shown to be specific for pharyngeal cells in vitro, little is known about functions of the three pili in bacterial pathogenesis. This is mainly due to a lack of in vivo models of corynebacterial infection. As an alternative to rodent models as mice do not have functional receptors for diphtheria toxin, we sought to use Caenorhabditis elegans as a model host for C. diphtheriae. Preliminary data shows that when infected with C. diphtheriae isolates that contain only pilus genes or no toxin gene, C. elegans exhibited significantly reduced mortality as compared to those infected with the type strain or C. diphtheriae isolates that contain both virulence genes. Importantly, nontoxigenic strains that lack both pilus and toxin genes are more attenuated in the nematode model. My work aims to examine the hypothesis that pili and toxin are major virulent determinants of this deadly pathogen. The results generated will shed light onto the molecular basis of corynebacterial virulence and infection and provide insight into the role of Gram-positive pili in bacterial pathogenesis.

 Search pubmed for papers by M Broadway and H Ton-That

Research Info

Molecular Basis of Corynebacterium diphtheriae Virulence and Infection in the Caenorhabditis elegans Models Host