Research in the Totten laboratory focuses the molecular pathogenesis of sexually
transmitted bacteria as well as the discovery of novel bacteria associated
with idiopathic reproductive tract infections. We have characterized
several virulence factors of Haemophilus ducreyi, including a toxin
that damages epithelial and immune cells, which might explain, in part, the
tissue damage characteristic of chancroid, the genital ulcer disease caused
by this organism. We are currently analyzing the role of these
virulence factors in the pathogenesis of chancroid using tissue culture and
animal models. We are also studying the molecular pathogenesis of infection
with Mycoplasma genitalium, a newly recognized STD pathogen that has
the smallest genome of any known free-living cellular organism. We have
shown that this bacterium is able to persist for months, and even years, in
the female genital tract, and are thus investigating the mechanisms this bacterium
uses to evade the host immune response to persist. We have shown extensive
variation in the genes for two surface exposed proteins in the complex adhesin
organelle of M. genitalium and have demonstrated that this variation
is consistent with recombination with archived partial copies of these genes
located at distant sites on its small chromosome. We hypothesize that
this gene variation leads to antigenic, and possibly phase variation, and are
currently investigating the mechanism used for this variation and effect on
immune escape. Finally, we are exploring the association of novel, and
even previously uncultured bacteria with idiopathic STD syndromes. For
example, using an organism-specific PCR assays developed in the Totten laboratory,
we demonstrated an association of Mycoplasma genitalium with urethritis,
cervicitis, and endometritis and the association of Ureaplasma urealyticum with
urethritis in men. Using broad range ribosomal DNA PCR assays, followed by
cloning, sequencing and in silico analysis, we also have uncovered
novel bacteria able to infect the upper reproductive tract in women. Our
current studies pursuing these exciting findings might uncover new fastidious
and possibly previously uncultured bacteria associated with serious reproductive
tract disease in women.