The Great Escape

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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.

Related papers

Chlamydia trachomatis cellular exit alters interactions with host dendritic cells
Sherrid AM & Hybiske K. Infect Immun (2017). PubMed | Journal

Extrusions are phagocytosed and promote Chlamydia survival within macrophages
Zuck M, Ellis T, Venida A, Hybiske K. Cell Microbiol (2017). PubMed | Journal

Conservation of extrusion as an exit mechanism for Chlamydia
Zuck M, Sherrid A, Suchland R, Ellis T, Hybiske K. Pathog Dis (2016). PubMed | Journal

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

Mechanisms of host cell exit by the intracellular bacterium Chlamydia
Hybiske K & Stephens RS. Proc Natl Acad Sci USA (2007). PubMed | Journal

 

Functional Genetics

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. 

Related papers

Expanding the molecular toolkit for Chlamydia
Hybiske K. Cell Host Microbe (2015). PubMed | Journal

 
 

Chlamydia–Host Interactions

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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.

Related papers

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. bioRxiv (2018). bioRxiv

Direct visualization of the expression and localization of chlamydial effector proteins within infected host cells
Wang X, Hybiske K, Stephens RS. Pathog Dis (2018). PubMed | Journal

Using fluorescent proteins to visualize and quantitate Chlamydia vacuole growth dynamics in living cells
Zuck M, Feng C, Hybiske K. J Vis Exp (2015). PubMed | Journal

 

Chlambase

  ChlamBase  is an open database and encourages data contributions from the Chlamydia research community. Contribute today, and your updates will be instantly visible to the field!

ChlamBase is an open database and encourages data contributions from the Chlamydia research community. Contribute today, and your updates will be instantly visible to the field!

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

  • RB/EB expression

  • 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).

Related papers

Coming soon

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