Polarized Chlamydial Cell Division in the Absence of FtsZ Chlamydia is an obligate intracellular bacterial pathogen that causes a range of serious diseases in humans. In developed countries, Chlamydia trachomatis is the primary cause of bacterial sexually transmitted infections (STI) whereas Chlamydia pneumoniae causes community-acquired respiratory infections. In developing countries, C. trachomatis is not only a significant cause of STI, 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 and possibly atherosclerosis and adult onset asthma for C. pneumoniae. Consequently, 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. This is a common trait amongst bacteria that evolve to obligate intracellular growth. However, Chlamydia has also lost genes that are considered essential in other bacteria. This proposal outlines a series of studies to investigate the essential process of chlamydial cell division. Chlamydia lacks the gene ftsZ, which encodes the bacterial tubulin-like homolog that is critical for organizing the cell division machinery at the site of division. Thus, how Chlamydia divides is an intriguing microbiological question. We have previously proposed that Chlamydia has substituted the bacterial actin-like homolog MreB for the function of FtsZ. This is unusual for many reasons, one of which is that MreB is important in imparting the rod shape to certain types of bacteria such as E. coli. Chlamydia is a round, coccoid bacterium yet encodes multiple rod-shape determining proteins. Recent evidence from our lab and others suggests that Chlamydia uses these proteins for cell division. Yet, the assumption has been that Chlamydia still utilizes the classic binary fission mechanism to separate daughter cells. Rather, new data from our labs have revealed that Chlamydia uses a polarized budding mechanism similar to yeast to accomplish division. Budding is rare in bacteria, and we intend to use Chlamydia as a model system to understand how budding occurs. We propose a series of experiments to understand the role of bacterial cytoskeletal proteins in bacterial budding as well as how they are regulated and with what other proteins they interact. Because budding is rare, any unique targets represent ideal candidates for anti-chlamydial antibiotic development that would have limited effects on normal flora.

Public Health Relevance

Polarized Chlamydial Cell Division in the Absence of FtsZ Chlamydiae are important pathogens of humans and significant causes of morbidity, causing a range of illnesses including sexually transmitted diseases, trachoma, pneumonia, and other respiratory tract infections. Many of the basic microbiological processes of Chlamydia remain poorly characterized in part because these bacteria often lack key proteins involved in these processes. The work proposed here outlines a series of studies to address these gaps in knowledge that will potentially facilitate rational drug design to limit effects of anti-chlamydial treatment on normal flora of the human host.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Unknown (R35)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Gindhart, Joseph G
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Nebraska Medical Center
Schools of Medicine
United States
Zip Code
Olson, Macy G; Goldammer, Megan; Gauliard, Emilie et al. (2018) A Bacterial Adenylate Cyclase-Based Two-Hybrid System Compatible with Gateway® Cloning. Methods Mol Biol 1794:75-96
Ouellette, Scot P (2018) Feasibility of a Conditional Knockout System for Chlamydia Based on CRISPR Interference. Front Cell Infect Microbiol 8:59