Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive <italic toggle="yes">Chlamydia trachomatis</italic> Biovars

ABSTRACT Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes blinding trachoma and sexually transmitted disease. C. trachomatis isolates are classified into 2 biovars—lymphogranuloma venereum (LGV) and trachoma—which are distinguished biologically by their natural host...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Michael John Patton, Chih-Yu Chen, Chunfu Yang, Stuart McCorrister, Chris Grant, Garrett Westmacott, Xin-Yong Yuan, Estela Ochoa, Robert Fariss, William M. Whitmire, John H. Carlson, Harlan D. Caldwell, Grant McClarty
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Chlamydia trachomatis plasmid proteomics virulence factors Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/db4d519280fe422684f8f3e8c09bfe61
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:db4d519280fe422684f8f3e8c09bfe61
record_format	dspace
spelling	oai:doaj.org-article:db4d519280fe422684f8f3e8c09bfe612021-11-15T15:53:25ZPlasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive <italic toggle="yes">Chlamydia trachomatis</italic> Biovars10.1128/mBio.02164-172150-7511https://doaj.org/article/db4d519280fe422684f8f3e8c09bfe612018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02164-17https://doaj.org/toc/2150-7511ABSTRACT Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes blinding trachoma and sexually transmitted disease. C. trachomatis isolates are classified into 2 biovars—lymphogranuloma venereum (LGV) and trachoma—which are distinguished biologically by their natural host cell infection tropism. LGV biovars infect macrophages and are invasive, whereas trachoma biovars infect oculo-urogenital epithelial cells and are noninvasive. The C. trachomatis plasmid is an important virulence factor in the pathogenesis of these infections. Central to its pathogenic role is the transcriptional regulatory function of the plasmid protein Pgp4, which regulates the expression of plasmid and chromosomal virulence genes. As many gene regulatory functions are post-transcriptional, we employed a comparative proteomic study of cells infected with plasmid-cured C. trachomatis serovars A and D (trachoma biovar), a L2 serovar (LGV biovar), and the L2 serovar transformed with a plasmid containing a nonsense mutation in pgp4 to more completely elucidate the effects of the plasmid on chlamydial infection biology. Our results show that the Pgp4-dependent elevations in the levels of Pgp3 and a conserved core set of chromosomally encoded proteins are remarkably similar for serovars within both C. trachomatis biovars. Conversely, we found a plasmid-dependent, Pgp4-independent, negative regulation in the expression of the chlamydial protease-like activity factor (CPAF) for the L2 serovar but not the A and D serovars. The molecular mechanism of plasmid-dependent negative regulation of CPAF expression in the LGV serovar is not understood but is likely important to understanding its macrophage infection tropism and invasive infection nature. IMPORTANCE The Chlamydia trachomatis plasmid is an important virulence factor in the pathogenesis of chlamydial infection. It is known that plasmid protein 4 (Pgp4) functions in the transcriptional regulation of the plasmid virulence protein 3 (Pgp3) and multiple chromosomal loci of unknown function. Since many gene regulatory functions can be post-transcriptional, we undertook a comparative proteomic analysis to better understand the plasmid’s role in chlamydial and host protein expression. We report that Pgp4 is a potent and specific master positive regulator of a common core of plasmid and chromosomal virulence genes shared by multiple C. trachomatis serovars. Notably, we show that the plasmid is a negative regulator of the expression of the chlamydial virulence factor CPAF. The plasmid regulation of CPAF is independent of Pgp4 and restricted to a C. trachomatis macrophage-tropic strain. These findings are important because they define a previously unknown role for the plasmid in the pathophysiology of invasive chlamydial infection.Michael John PattonChih-Yu ChenChunfu YangStuart McCorristerChris GrantGarrett WestmacottXin-Yong YuanEstela OchoaRobert FarissWilliam M. WhitmireJohn H. CarlsonHarlan D. CaldwellGrant McClartyAmerican Society for MicrobiologyarticleChlamydia trachomatisplasmidproteomicsvirulence factorsMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chlamydia trachomatis plasmid proteomics virulence factors Microbiology QR1-502
spellingShingle	Chlamydia trachomatis plasmid proteomics virulence factors Microbiology QR1-502 Michael John Patton Chih-Yu Chen Chunfu Yang Stuart McCorrister Chris Grant Garrett Westmacott Xin-Yong Yuan Estela Ochoa Robert Fariss William M. Whitmire John H. Carlson Harlan D. Caldwell Grant McClarty Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive <italic toggle="yes">Chlamydia trachomatis</italic> Biovars
description	ABSTRACT Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes blinding trachoma and sexually transmitted disease. C. trachomatis isolates are classified into 2 biovars—lymphogranuloma venereum (LGV) and trachoma—which are distinguished biologically by their natural host cell infection tropism. LGV biovars infect macrophages and are invasive, whereas trachoma biovars infect oculo-urogenital epithelial cells and are noninvasive. The C. trachomatis plasmid is an important virulence factor in the pathogenesis of these infections. Central to its pathogenic role is the transcriptional regulatory function of the plasmid protein Pgp4, which regulates the expression of plasmid and chromosomal virulence genes. As many gene regulatory functions are post-transcriptional, we employed a comparative proteomic study of cells infected with plasmid-cured C. trachomatis serovars A and D (trachoma biovar), a L2 serovar (LGV biovar), and the L2 serovar transformed with a plasmid containing a nonsense mutation in pgp4 to more completely elucidate the effects of the plasmid on chlamydial infection biology. Our results show that the Pgp4-dependent elevations in the levels of Pgp3 and a conserved core set of chromosomally encoded proteins are remarkably similar for serovars within both C. trachomatis biovars. Conversely, we found a plasmid-dependent, Pgp4-independent, negative regulation in the expression of the chlamydial protease-like activity factor (CPAF) for the L2 serovar but not the A and D serovars. The molecular mechanism of plasmid-dependent negative regulation of CPAF expression in the LGV serovar is not understood but is likely important to understanding its macrophage infection tropism and invasive infection nature. IMPORTANCE The Chlamydia trachomatis plasmid is an important virulence factor in the pathogenesis of chlamydial infection. It is known that plasmid protein 4 (Pgp4) functions in the transcriptional regulation of the plasmid virulence protein 3 (Pgp3) and multiple chromosomal loci of unknown function. Since many gene regulatory functions can be post-transcriptional, we undertook a comparative proteomic analysis to better understand the plasmid’s role in chlamydial and host protein expression. We report that Pgp4 is a potent and specific master positive regulator of a common core of plasmid and chromosomal virulence genes shared by multiple C. trachomatis serovars. Notably, we show that the plasmid is a negative regulator of the expression of the chlamydial virulence factor CPAF. The plasmid regulation of CPAF is independent of Pgp4 and restricted to a C. trachomatis macrophage-tropic strain. These findings are important because they define a previously unknown role for the plasmid in the pathophysiology of invasive chlamydial infection.
format	article
author	Michael John Patton Chih-Yu Chen Chunfu Yang Stuart McCorrister Chris Grant Garrett Westmacott Xin-Yong Yuan Estela Ochoa Robert Fariss William M. Whitmire John H. Carlson Harlan D. Caldwell Grant McClarty
author_facet	Michael John Patton Chih-Yu Chen Chunfu Yang Stuart McCorrister Chris Grant Garrett Westmacott Xin-Yong Yuan Estela Ochoa Robert Fariss William M. Whitmire John H. Carlson Harlan D. Caldwell Grant McClarty
author_sort	Michael John Patton
title	Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive <italic toggle="yes">Chlamydia trachomatis</italic> Biovars
title_short	Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive <italic toggle="yes">Chlamydia trachomatis</italic> Biovars
title_full	Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive <italic toggle="yes">Chlamydia trachomatis</italic> Biovars
title_fullStr	Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive <italic toggle="yes">Chlamydia trachomatis</italic> Biovars
title_full_unstemmed	Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive <italic toggle="yes">Chlamydia trachomatis</italic> Biovars
title_sort	plasmid negative regulation of cpaf expression is pgp4 independent and restricted to invasive <italic toggle="yes">chlamydia trachomatis</italic> biovars
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/db4d519280fe422684f8f3e8c09bfe61
work_keys_str_mv	AT michaeljohnpatton plasmidnegativeregulationofcpafexpressionispgp4independentandrestrictedtoinvasiveitalictoggleyeschlamydiatrachomatisitalicbiovars AT chihyuchen plasmidnegativeregulationofcpafexpressionispgp4independentandrestrictedtoinvasiveitalictoggleyeschlamydiatrachomatisitalicbiovars AT chunfuyang plasmidnegativeregulationofcpafexpressionispgp4independentandrestrictedtoinvasiveitalictoggleyeschlamydiatrachomatisitalicbiovars AT stuartmccorrister plasmidnegativeregulationofcpafexpressionispgp4independentandrestrictedtoinvasiveitalictoggleyeschlamydiatrachomatisitalicbiovars AT chrisgrant plasmidnegativeregulationofcpafexpressionispgp4independentandrestrictedtoinvasiveitalictoggleyeschlamydiatrachomatisitalicbiovars AT garrettwestmacott plasmidnegativeregulationofcpafexpressionispgp4independentandrestrictedtoinvasiveitalictoggleyeschlamydiatrachomatisitalicbiovars AT xinyongyuan plasmidnegativeregulationofcpafexpressionispgp4independentandrestrictedtoinvasiveitalictoggleyeschlamydiatrachomatisitalicbiovars AT estelaochoa plasmidnegativeregulationofcpafexpressionispgp4independentandrestrictedtoinvasiveitalictoggleyeschlamydiatrachomatisitalicbiovars AT robertfariss plasmidnegativeregulationofcpafexpressionispgp4independentandrestrictedtoinvasiveitalictoggleyeschlamydiatrachomatisitalicbiovars AT williammwhitmire plasmidnegativeregulationofcpafexpressionispgp4independentandrestrictedtoinvasiveitalictoggleyeschlamydiatrachomatisitalicbiovars AT johnhcarlson plasmidnegativeregulationofcpafexpressionispgp4independentandrestrictedtoinvasiveitalictoggleyeschlamydiatrachomatisitalicbiovars AT harlandcaldwell plasmidnegativeregulationofcpafexpressionispgp4independentandrestrictedtoinvasiveitalictoggleyeschlamydiatrachomatisitalicbiovars AT grantmcclarty plasmidnegativeregulationofcpafexpressionispgp4independentandrestrictedtoinvasiveitalictoggleyeschlamydiatrachomatisitalicbiovars
_version_	1718427309454655488

Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive <italic toggle="yes">Chlamydia trachomatis</italic> Biovars

Ejemplares similares