Journal article
Identification and Preliminary Characterization of Novel Type III Secreted Effector Proteins in Chlamydia trachomatis
Infection and immunity, Vol.91(7), e0049122
07/18/2023
DOI: 10.1128/iai.00491-22
PMCID: PMC10353436
PMID: 37347192
Abstract
Chlamydia trachomatis is an obligate intracellular pathogen that replicates in a host-derived vacuole termed the inclusion. Central to pathogenesis is a type III secretion system that translocates effector proteins into the host cell, which are predicted to play major roles in host cell invasion, nutrient acquisition, and immune evasion. However, until recently, the genetic intractability of C. trachomatis hindered identification and characterization of these important virulence factors. Here, we sought to expand the repertoire of identified effector proteins and confirm they are secreted during C. trachomatis infection. Utilizing bioinformatics, we identified 18 candidate substrates that had not been previously assessed for secretion, of which we show four to be secreted, using Yersinia pseudotuberculosis as a surrogate host. Using adenylate cyclase (CyaA), BlaM, and glycogen synthase kinase (GSK) secretion assays, we identified nine novel substrates that were secreted in at least one assay. Interestingly, only three of the substrates, shown to be translocated by C. trachomatis, were similarly secreted by Y. pseudotuberculosis. Using large-scale screens to determine subcellular localization and identify effectors that perturb crucial host cell processes, we identified one novel substrate, CT392, that is toxic when heterologously expressed in Saccharomyces cerevisiae. Toxicity required both the N- and C-terminal regions of the protein. Additionally, we show that these newly described substrates traffic to distinct host cell compartments, including vesicles and the cytoplasm. Collectively, our study expands the known repertoire of C. trachomatis secreted factors and highlights the importance of testing for secretion in the native host using multiple secretion assays when possible.
Details
- Title: Subtitle
- Identification and Preliminary Characterization of Novel Type III Secreted Effector Proteins in Chlamydia trachomatis
- Creators
- Paige N McCaslin - University of IowaShelby E Andersen - University of IowaCarolina M Icardi - University of IowaRobert Faris - University of IowaBrianna Steiert - University of IowaParker Smith - University of IowaJawad Haider - University of IowaMary M Weber - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.91(7), e0049122
- DOI
- 10.1128/iai.00491-22
- PMID
- 37347192
- PMCID
- PMC10353436
- eISSN
- 1098-5522
- Grant note
- DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: R01 AI155434; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: R01 AI150812; name: University of Iowa Stead Family Scholars Program; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: AI007511
- Language
- English
- Electronic publication date
- 06/22/2023
- Date published
- 07/18/2023
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology
- Record Identifier
- 9984436280302771
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