Project Abstract: Investigating the Function of Bacterial Cytoskeletal Elements in the Division and
Growth of the FtsZ-less Chlamydia
Chlamydia is an obligate intracellular bacterial pathogen that causes a range of serious diseases in
humans. In developed countries, Chlamydia trachomatis is the leading cause of bacterial sexually transmitted
infections (STI). In developing countries, C. trachomatis is not only a significant cause of STI, but it is also
responsible for the primary cause of infectious preventable blindness, trachoma. The major concern of
chlamydial infections is that they are often asymptomatic and undiagnosed, which can lead to chronic
sequelae. These include pelvic inflammatory disease, tubal factor infertility, and reactive arthritis for C.
trachomatis. Chlamydial diseases remain a significant burden on health care systems around the world.
In adapting to obligate intracellular growth, Chlamydia has significantly reduced its genome size and
eliminated genes from various pathways as it relies on the host cell for its metabolic needs. One such
“essential” gene that Chlamydia has eliminated is FtsZ, the central organizer of the division septum during
binary fission. A major focus of the lab is to understand how Chlamydia divides. Previously, we have
demonstrated that Chlamydia divides by an MreB-dependent polarized division mechanism that relies, in part,
on the unique N-terminal domain of chlamydial MreB. This pathogen also alternates between different
functional and morphological forms during its normal growth, also referred to as its developmental cycle.
These observations, combined with its obligate intracellular dependence, make Chlamydia a difficult, but
fascinating, organism with which to work. Nonetheless, recent development of genetic tools to mechanistically
study chlamydiae has significantly enhanced our understanding of this pathogen. The current application
goals are designed to leverage prior work investigating the function of chlamydial cytoskeletal elements. Goal
1: We will investigate how MreB is maintained at the division septum after its initial recruitment to a specific
site on the bacterial surface as well as the contributions of various phospholipids to this process. We will also
determine factors that contribute to how daughter cell outgrowth occurs during the budding process. Goal 2:
We will investigate a novel bactofilin cytoskeletal element we identified that functions in maintaining cell size.
We seek to understand its function in regulating cell size in Chlamydia by interrogating specific domains
necessary for its effects and identifying interaction partners that contribute to cell size. We hypothesize that,
given the absence of FtsZ in these organisms and their use of MreB in its place, the mechanisms of cell size
control will be unique in these bacteria. Consequently, our results may lead to the identification of Chlamydia-
unique targets for antimicrobial development. This will limit the impact of broad spectrum antibiotics on the
microbiome during treatment of chlamydia infections. More fundamentally, findings from the proposed
research will enhance our understanding of the evolutionary strategies bacteria employ to regulate a critical
physiological function.