The Great Escape
extrusion strategy of chlamydia exit
Intracellular pathogens have evolved numerous strategies for promoting their exit from host cells, consistent with the essential role of exit for pathogenesis. Yet despite this fundamental importance, microbial exit largely remains an unexplored research area. Efforts in our lab aim to advance understanding of this new theme.
Our pioneering discoveries forged the current understanding of Chlamydia exit from host cells. Chlamydiae possess two mechanisms for accomplishing cellular escape that are mutually exclusive: extrusion and lysis. Extrusion is a packaged release of Chlamydiain which the bacteria are pinched off from the host cell into a membrane-encased compartment, a process that leaves the original host cell intact. Extrusions are novel structures that enhance the biology of Chlamydia infection in many fascinating ways, such as serving as a ‘stealth shuttle’ as these bacteria attempt to elude the host immune system.
Actin recruitment to the Chlamydia inclusion is spatiotemporally regulated by a mechanism that requires host and bacterial factors
Chin E, Kirker K, Zuck M, James G, Hybiske K. PLoS One (2012). PubMed | Journal
Discovery of Chlamydia virulence factors
Genome-wide discovery and characterization of virulence determinants for Chlamydia remains a major unaddressed research area. Through recent landmark advances in genetic manipulation of Chlamydia, and a rich collaboration with Scott Hefty and Dan Rockey that exploits new methodologies for genetic engineering in Chlamydia, we are working to discover the Chlamydia genes and host protein targets that play critical roles in Chlamydia infection and pathogenesis.
combining genetics & proteomics to illuminate novel chlamydia-host interactions
Successful infection of host cells by Chlamydia requires continuous interactions between scores of bacteria and host proteins, in a manner that ultimately benefits the pathogen. Identification and characterization of these protein interactions is a high priority research area, and may spearhead the development of novel antimicrobials.
We are developing and exploiting novel proteomic systems to probe unique interactions between intracellular Chlamydia and host cell targets.
Proximity-dependent proteomics of the Chlamydia trachomatis inclusion membrane reveals functional interactions with endoplasmic reticulum exit sites
Dickinson MS, Anderson LN, Webb-Robertson BJ, Hansen JR, Smith RD, Wright AT, Hybiske K. PLoS Pathogens (2019). Journal
a curated model organism database for the Chlamydia research community
Together with the Su Lab, experts in aggregating community acquired research knowledge into open source databases, we are proud to announce the launch of ChlamBase.org. ChlamBase is a fork of WikiGenomes.org, a Wikidata-backed database of over 100 NCBI microbial reference genomes. The goal of ChlamBase is to provide a streamlined, researcher-curated database of genetic and proteomic knowledge for the Chlamydia research community. This database uniquely offers information not available on other services, such as:
Current gene annotations
Orthologous gene comparisons and alignments
Annotations of Chlamydia mutants
Developmental expression timing
Host and bacterial protein interactions
STI Structure-based drug design
development of novel antimicrobials to treat sexually transmitted infections
We are part of a multi-laboratory team at the University of Washington focused on developing novel antimicrobial drugs to treat sexually transmitted infections (STIs) caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium. From the unique strengths of our team, we are uniquely poised to combat the emerging threats of untreatable N. gonorrhoeae and M. genitalium infections. We employ a structure-based approach, using crystal structures and virtual models provided by the Seattle Structural Genomics Center for Infectious Disease (SSGCID).