Single-Inclusion Kinetics of <italic toggle="yes">Chlamydia trachomatis</italic> Development

ABSTRACT The obligate intracellular bacterial pathogen Chlamydia trachomatis is reliant on a developmental cycle consisting of two cell forms, termed the elementary body (EB) and the reticulate body (RB). The EB is infectious and utilizes a type III secretion system and preformed effector proteins d...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Travis J. Chiarelli, Nicole A. Grieshaber, Anders Omsland, Christopher H. Remien, Scott S. Grieshaber
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	bacterial development chlamydia live-cell imaging mathematical modeling infectious disease Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8c96fd0e75d445698feeebbf250d34df
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8c96fd0e75d445698feeebbf250d34df
record_format	dspace
spelling	oai:doaj.org-article:8c96fd0e75d445698feeebbf250d34df2021-12-02T18:44:44ZSingle-Inclusion Kinetics of <italic toggle="yes">Chlamydia trachomatis</italic> Development10.1128/mSystems.00689-202379-5077https://doaj.org/article/8c96fd0e75d445698feeebbf250d34df2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00689-20https://doaj.org/toc/2379-5077ABSTRACT The obligate intracellular bacterial pathogen Chlamydia trachomatis is reliant on a developmental cycle consisting of two cell forms, termed the elementary body (EB) and the reticulate body (RB). The EB is infectious and utilizes a type III secretion system and preformed effector proteins during invasion, but it does not replicate. The RB replicates in the host cell but is noninfectious. This developmental cycle is central to chlamydial pathogenesis. In this study, we developed mathematical models of the developmental cycle that account for potential factors influencing RB-to-EB cell type switching during infection. Our models predicted that two categories of regulatory signals for RB-to-EB development could be differentiated experimentally, an “intrinsic” cell-autonomous program inherent to each RB and an “extrinsic” environmental signal to which RBs respond. To experimentally differentiate between mechanisms, we tracked the expression of C. trachomatis development-specific promoters in individual inclusions using fluorescent reporters and live-cell imaging. These experiments indicated that EB production was not influenced by increased multiplicity of infection or by superinfection, suggesting the cycle follows an intrinsic program that is not directly controlled by environmental factors. Additionally, live-cell imaging revealed that EB development is a multistep process linked to RB growth rate and cell division. The formation of EBs followed a progression with expression from the euo and ihtA promoters evident in RBs, while expression from the promoter for hctA was apparent in early EBs/IBs. Finally, expression from the promoters for the true late genes, hctB, scc2, and tarp, was evident in the maturing EB. IMPORTANCE Chlamydia trachomatis is an obligate intracellular bacterium that can cause trachoma, cervicitis, urethritis, salpingitis, and pelvic inflammatory disease. To establish infection in host cells, Chlamydia must complete a multiple-cell-type developmental cycle. The developmental cycle consists of specialized cells, the EB cell, which mediates infection of new host cells, and the RB cell, which replicates and eventually produces more EB cells to mediate the next round of infection. By developing and testing mathematical models to discriminate between two competing hypotheses for the nature of the signal controlling RB-to-EB cell type switching, we demonstrate that RB-to-EB development follows a cell-autonomous program that does not respond to environmental cues. Additionally, we show that RB-to-EB development is a function of chlamydial growth and division. This study serves to further our understanding of the chlamydial developmental cycle that is central to the bacterium’s pathogenesis.Travis J. ChiarelliNicole A. GrieshaberAnders OmslandChristopher H. RemienScott S. GrieshaberAmerican Society for Microbiologyarticlebacterial developmentchlamydialive-cell imagingmathematical modelinginfectious diseaseMicrobiologyQR1-502ENmSystems, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	bacterial development chlamydia live-cell imaging mathematical modeling infectious disease Microbiology QR1-502
spellingShingle	bacterial development chlamydia live-cell imaging mathematical modeling infectious disease Microbiology QR1-502 Travis J. Chiarelli Nicole A. Grieshaber Anders Omsland Christopher H. Remien Scott S. Grieshaber Single-Inclusion Kinetics of <italic toggle="yes">Chlamydia trachomatis</italic> Development
description	ABSTRACT The obligate intracellular bacterial pathogen Chlamydia trachomatis is reliant on a developmental cycle consisting of two cell forms, termed the elementary body (EB) and the reticulate body (RB). The EB is infectious and utilizes a type III secretion system and preformed effector proteins during invasion, but it does not replicate. The RB replicates in the host cell but is noninfectious. This developmental cycle is central to chlamydial pathogenesis. In this study, we developed mathematical models of the developmental cycle that account for potential factors influencing RB-to-EB cell type switching during infection. Our models predicted that two categories of regulatory signals for RB-to-EB development could be differentiated experimentally, an “intrinsic” cell-autonomous program inherent to each RB and an “extrinsic” environmental signal to which RBs respond. To experimentally differentiate between mechanisms, we tracked the expression of C. trachomatis development-specific promoters in individual inclusions using fluorescent reporters and live-cell imaging. These experiments indicated that EB production was not influenced by increased multiplicity of infection or by superinfection, suggesting the cycle follows an intrinsic program that is not directly controlled by environmental factors. Additionally, live-cell imaging revealed that EB development is a multistep process linked to RB growth rate and cell division. The formation of EBs followed a progression with expression from the euo and ihtA promoters evident in RBs, while expression from the promoter for hctA was apparent in early EBs/IBs. Finally, expression from the promoters for the true late genes, hctB, scc2, and tarp, was evident in the maturing EB. IMPORTANCE Chlamydia trachomatis is an obligate intracellular bacterium that can cause trachoma, cervicitis, urethritis, salpingitis, and pelvic inflammatory disease. To establish infection in host cells, Chlamydia must complete a multiple-cell-type developmental cycle. The developmental cycle consists of specialized cells, the EB cell, which mediates infection of new host cells, and the RB cell, which replicates and eventually produces more EB cells to mediate the next round of infection. By developing and testing mathematical models to discriminate between two competing hypotheses for the nature of the signal controlling RB-to-EB cell type switching, we demonstrate that RB-to-EB development follows a cell-autonomous program that does not respond to environmental cues. Additionally, we show that RB-to-EB development is a function of chlamydial growth and division. This study serves to further our understanding of the chlamydial developmental cycle that is central to the bacterium’s pathogenesis.
format	article
author	Travis J. Chiarelli Nicole A. Grieshaber Anders Omsland Christopher H. Remien Scott S. Grieshaber
author_facet	Travis J. Chiarelli Nicole A. Grieshaber Anders Omsland Christopher H. Remien Scott S. Grieshaber
author_sort	Travis J. Chiarelli
title	Single-Inclusion Kinetics of <italic toggle="yes">Chlamydia trachomatis</italic> Development
title_short	Single-Inclusion Kinetics of <italic toggle="yes">Chlamydia trachomatis</italic> Development
title_full	Single-Inclusion Kinetics of <italic toggle="yes">Chlamydia trachomatis</italic> Development
title_fullStr	Single-Inclusion Kinetics of <italic toggle="yes">Chlamydia trachomatis</italic> Development
title_full_unstemmed	Single-Inclusion Kinetics of <italic toggle="yes">Chlamydia trachomatis</italic> Development
title_sort	single-inclusion kinetics of <italic toggle="yes">chlamydia trachomatis</italic> development
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/8c96fd0e75d445698feeebbf250d34df
work_keys_str_mv	AT travisjchiarelli singleinclusionkineticsofitalictoggleyeschlamydiatrachomatisitalicdevelopment AT nicoleagrieshaber singleinclusionkineticsofitalictoggleyeschlamydiatrachomatisitalicdevelopment AT andersomsland singleinclusionkineticsofitalictoggleyeschlamydiatrachomatisitalicdevelopment AT christopherhremien singleinclusionkineticsofitalictoggleyeschlamydiatrachomatisitalicdevelopment AT scottsgrieshaber singleinclusionkineticsofitalictoggleyeschlamydiatrachomatisitalicdevelopment
_version_	1718377690176684032

Single-Inclusion Kinetics of <italic toggle="yes">Chlamydia trachomatis</italic> Development

Ejemplares similares