Original Research ARTICLE
Genetic inactivation of Chlamydia trachomatis inclusion membrane protein CT228 alters MYPT1 recruitment, extrusion production and longevity of infection
- 1Oklahoma State University, United States
- 2Southern Illinois University Carbondale, United States
Chlamydia trachomatis is an obligate intracellular pathogen with global health and economic impact. Upon infection, C. trachomatis resides within a protective niche, the inclusion, wherein it replicates and usurps host cell machinery and resources. The inclusion membrane is the key host-pathogen interface that governs specific protein-protein interactions to manipulate host signaling pathways. At the conclusion of the infection cycle, C. trachomatis exits the host cell via lysis or extrusion. Extrusion depends on the phosphorylation state of myosin light chain 2 (MLC2); the extent of phosphorylation is determined by the ongoing opposing activities of myosin phosphatase (MYPT1) and myosin kinase (MLCK). Previously, it was shown that MYPT1 is recruited to the inclusion and interacts with CT228 for regulation of host cell egress.
In this study, we generated a targeted chromosomal mutation of CT228 (L2-ΔCT228) using the TargeTron system and demonstrate a loss of MYPT1 recruitment and increase in extrusion production in vitro. Mutation of CT228 did not affect chlamydial growth in cell culture or recruitment of MLC2. Moreover, we document a delay in clearance of L2-ΔCT228 during murine intravaginal infection as well as a reduction in both systemic humoral response and reproductive tract mucinous changes, relative to L2-wild type. Taken together, the data suggest that loss of MYPT1 recruitment (as a result of CT228 disruption) regulates to the degree of host cell exit via extrusion and affects the longevity of infection in vivo.
Keywords: Chlamydia, Extrusion, Lymphogranuloma Venereum, L2 serovar, Sexually transmitted infection, Urogenital infection, CT228, mouse infection
Received: 30 Jul 2018;
Accepted: 08 Nov 2018.
Edited by:Rey Carabeo, Washington State University, United States
Reviewed by:George Liechti, Uniformed Services University of the Health Sciences, United States
Ashok Aiyar, LSU Health Sciences Center New Orleans, United States
Maria T. Damiani, CONICET - UNCuyo
Copyright: © 2018 Shaw, Key, Snider, Shaw, Fisher and Lutter. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Dr. Jennifer H. Shaw, Oklahoma State University, Stillwater, United States, email@example.com
Dr. Erika I. Lutter, Oklahoma State University, Stillwater, United States, firstname.lastname@example.org