The T3SS structural and effector genes of Chlamydia trachomatis are expressed in distinct phenotypic cell forms

Bacteria in the Chlamydiales order are obligate intracellular parasites of eukaryotic cells. Within this order, the genus Chlamydia contains the causative agents of a number of clinically important infections in humans. Biovars of Chlamydia trachomatis are the causative agents of trachoma and the le...

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Main Authors: Nicole A. Grieshaber, Cody Appa, Megan Ward, Alorah Grossman, Sean McCormik, Brendan S. Grieshaber, Travis Chiarelli, Hong Yang, Anders Omsland, Scott S. Grieshaber
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1579247/full
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author Nicole A. Grieshaber
Cody Appa
Megan Ward
Alorah Grossman
Sean McCormik
Brendan S. Grieshaber
Travis Chiarelli
Hong Yang
Anders Omsland
Scott S. Grieshaber
author_facet Nicole A. Grieshaber
Cody Appa
Megan Ward
Alorah Grossman
Sean McCormik
Brendan S. Grieshaber
Travis Chiarelli
Hong Yang
Anders Omsland
Scott S. Grieshaber
author_sort Nicole A. Grieshaber
collection DOAJ
description Bacteria in the Chlamydiales order are obligate intracellular parasites of eukaryotic cells. Within this order, the genus Chlamydia contains the causative agents of a number of clinically important infections in humans. Biovars of Chlamydia trachomatis are the causative agents of trachoma and the leading cause of preventable blindness worldwide, as well as sexually transmitted infections with the potential to cause pelvic inflammatory disease and infertility. Irrespective of the resulting disease, all chlamydial species share the same obligate intracellular life cycle and developmental cell forms. They are reliant on an infectious cycle consisting of at least three phenotypically distinct cell forms termed the reticulate body (RB), the intermediate body (IB), and the elementary body (EB). The EB is infectious but does not replicate. The RB replicates in the host cell but is non-infectious, while the IB is an intermediate form that transitions to the EB form. In this study, we ectopically expressed the transcriptional repressor Euo, the two nucleoid-associated proteins HctA and HctB, and the two-component sensor kinase CtcB in the RB. Transcriptional analysis using RNA-seq, differential expression clustering, and fluorescence in situ hybridization analysis shows that the chlamydial developmental cycle is driven by three distinct regulons corresponding to the RB, IB, or EB cell forms. Moreover, we show that the genes for the type III secretion system (T3SS) were cell type restricted, suggesting defined functional roles for the T3SS in specific cell forms.ImportanceChlamydia trachomatis, a sexually transmitted bacterial infection, poses a significant global health threat, causing over 100 million infections annually and leading to complications like ectopic pregnancy and infertility. This study investigates the gene expression patterns of C. trachomatis during its unique life cycle within human cells. As an obligate intracellular parasite, C. trachomatis transitions through distinct developmental stages—one for infection and dissemination, another for replication, and a third for transitioning back to the infectious form. By analyzing gene expression profiles at each stage, we identified key genes involved in these processes. Interestingly, our research also reveals the presence of two separate type III secretion system (T3SS) translocons expressed in distinct stages, suggesting their crucial roles in specific functions during the infection cycle.
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spelling doaj-art-362c0cd2339b4633843cef8d0b2c4e4c2025-08-20T03:48:51ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-05-011510.3389/fcimb.2025.15792471579247The T3SS structural and effector genes of Chlamydia trachomatis are expressed in distinct phenotypic cell formsNicole A. Grieshaber0Cody Appa1Megan Ward2Alorah Grossman3Sean McCormik4Brendan S. Grieshaber5Travis Chiarelli6Hong Yang7Anders Omsland8Scott S. Grieshaber9Department of Biological Sciences, University of Idaho, Moscow, ID, United StatesDepartment of Biological Sciences, University of Idaho, Moscow, ID, United StatesDepartment of Biological Sciences, University of Idaho, Moscow, ID, United StatesDepartment of Biological Sciences, University of Idaho, Moscow, ID, United StatesDepartment of Biological Sciences, University of Idaho, Moscow, ID, United StatesDepartment of Biological Sciences, University of Idaho, Moscow, ID, United StatesDepartment of Biological Sciences, University of Idaho, Moscow, ID, United StatesPaul G. Allen School for Global Health, Washington State University, Pullman, WA, United StatesPaul G. Allen School for Global Health, Washington State University, Pullman, WA, United StatesDepartment of Biological Sciences, University of Idaho, Moscow, ID, United StatesBacteria in the Chlamydiales order are obligate intracellular parasites of eukaryotic cells. Within this order, the genus Chlamydia contains the causative agents of a number of clinically important infections in humans. Biovars of Chlamydia trachomatis are the causative agents of trachoma and the leading cause of preventable blindness worldwide, as well as sexually transmitted infections with the potential to cause pelvic inflammatory disease and infertility. Irrespective of the resulting disease, all chlamydial species share the same obligate intracellular life cycle and developmental cell forms. They are reliant on an infectious cycle consisting of at least three phenotypically distinct cell forms termed the reticulate body (RB), the intermediate body (IB), and the elementary body (EB). The EB is infectious but does not replicate. The RB replicates in the host cell but is non-infectious, while the IB is an intermediate form that transitions to the EB form. In this study, we ectopically expressed the transcriptional repressor Euo, the two nucleoid-associated proteins HctA and HctB, and the two-component sensor kinase CtcB in the RB. Transcriptional analysis using RNA-seq, differential expression clustering, and fluorescence in situ hybridization analysis shows that the chlamydial developmental cycle is driven by three distinct regulons corresponding to the RB, IB, or EB cell forms. Moreover, we show that the genes for the type III secretion system (T3SS) were cell type restricted, suggesting defined functional roles for the T3SS in specific cell forms.ImportanceChlamydia trachomatis, a sexually transmitted bacterial infection, poses a significant global health threat, causing over 100 million infections annually and leading to complications like ectopic pregnancy and infertility. This study investigates the gene expression patterns of C. trachomatis during its unique life cycle within human cells. As an obligate intracellular parasite, C. trachomatis transitions through distinct developmental stages—one for infection and dissemination, another for replication, and a third for transitioning back to the infectious form. By analyzing gene expression profiles at each stage, we identified key genes involved in these processes. Interestingly, our research also reveals the presence of two separate type III secretion system (T3SS) translocons expressed in distinct stages, suggesting their crucial roles in specific functions during the infection cycle.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1579247/fullChlamydiaChlamydia developmental cyclebacterial differentiationtype III secretion systemsgene regulation
spellingShingle Nicole A. Grieshaber
Cody Appa
Megan Ward
Alorah Grossman
Sean McCormik
Brendan S. Grieshaber
Travis Chiarelli
Hong Yang
Anders Omsland
Scott S. Grieshaber
The T3SS structural and effector genes of Chlamydia trachomatis are expressed in distinct phenotypic cell forms
Frontiers in Cellular and Infection Microbiology
Chlamydia
Chlamydia developmental cycle
bacterial differentiation
type III secretion systems
gene regulation
title The T3SS structural and effector genes of Chlamydia trachomatis are expressed in distinct phenotypic cell forms
title_full The T3SS structural and effector genes of Chlamydia trachomatis are expressed in distinct phenotypic cell forms
title_fullStr The T3SS structural and effector genes of Chlamydia trachomatis are expressed in distinct phenotypic cell forms
title_full_unstemmed The T3SS structural and effector genes of Chlamydia trachomatis are expressed in distinct phenotypic cell forms
title_short The T3SS structural and effector genes of Chlamydia trachomatis are expressed in distinct phenotypic cell forms
title_sort t3ss structural and effector genes of chlamydia trachomatis are expressed in distinct phenotypic cell forms
topic Chlamydia
Chlamydia developmental cycle
bacterial differentiation
type III secretion systems
gene regulation
url https://www.frontiersin.org/articles/10.3389/fcimb.2025.1579247/full
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