Hypervirulent <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L<sub>2</sub>) and D Lineages

ABSTRACT Chlamydia trachomatis is an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence facto...

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Autores principales:	Naraporn Somboonna, Raymond Wan, David M. Ojcius, Matthew A. Pettengill, Sandeep J. Joseph, Alexander Chang, Ray Hsu, Timothy D. Read, Deborah Dean
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/514aa54432b64bba83cc363007c38c7c
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spelling	oai:doaj.org-article:514aa54432b64bba83cc363007c38c7c2021-11-15T15:38:50ZHypervirulent <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L<sub>2</sub>) and D Lineages10.1128/mBio.00045-112150-7511https://doaj.org/article/514aa54432b64bba83cc363007c38c7c2011-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00045-11https://doaj.org/toc/2150-7511ABSTRACT Chlamydia trachomatis is an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L2/434 and outbreak strain L2b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L2c, isolated from an MSM with severe hemorrhagic proctitis. L2c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, unlike the LGV strains described to date. Deep genome sequencing revealed that L2c was a recombinant of L2 and D strains with conserved clustered regions of genetic exchange, including a 78-kb region and a partial, yet functional, toxin gene that was lost with prolonged culture. Indels (insertions/deletions) were discovered in an ftsK gene promoter and in the tarp and hctB genes, which encode key proteins involved in replication, inclusion formation, and histone H1-like protein activity, respectively. Analyses suggest that these indels affect gene and/or protein function, supporting the in vitro and disease phenotypes. While recombination has been known to occur for C. trachomatis based on gene sequence analyses, we provide the first whole-genome evidence for recombination between a virulent, invasive LGV strain and a noninvasive common urogenital strain. Given the lack of a genetic system for producing stable C. trachomatis mutants, identifying naturally occurring recombinants can clarify gene function and provide opportunities for discovering avenues for genomic manipulation. IMPORTANCE Lymphogranuloma venereum (LGV) is a prevalent and debilitating sexually transmitted disease in developing countries, although there are significant ongoing outbreaks in Australia, Europe, and the United States among men who have sex with men (MSM). Relatively little is known about LGV virulence factors, and only two LGV genomes have been sequenced to date. We isolated an LGV strain from an MSM with severe hemorrhagic proctitis that was morphologically unique in tissue culture compared with other LGV strains. Bioinformatic and statistical analyses identified the strain as a recombinant of L2 and D strains with highly conserved clustered regions of genetic exchange. The unique culture morphology and, more importantly, disease phenotype could be traced to the genes involved in recombination. The findings have implications for bacterial species evolution and, in the case of ongoing LGV outbreaks, suggest that recombination is a mechanism for strain emergence that results in significant disease pathology.Naraporn SomboonnaRaymond WanDavid M. OjciusMatthew A. PettengillSandeep J. JosephAlexander ChangRay HsuTimothy D. ReadDeborah DeanAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 3 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Naraporn Somboonna Raymond Wan David M. Ojcius Matthew A. Pettengill Sandeep J. Joseph Alexander Chang Ray Hsu Timothy D. Read Deborah Dean Hypervirulent <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L<sub>2</sub>) and D Lineages
description	ABSTRACT Chlamydia trachomatis is an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L2/434 and outbreak strain L2b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L2c, isolated from an MSM with severe hemorrhagic proctitis. L2c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, unlike the LGV strains described to date. Deep genome sequencing revealed that L2c was a recombinant of L2 and D strains with conserved clustered regions of genetic exchange, including a 78-kb region and a partial, yet functional, toxin gene that was lost with prolonged culture. Indels (insertions/deletions) were discovered in an ftsK gene promoter and in the tarp and hctB genes, which encode key proteins involved in replication, inclusion formation, and histone H1-like protein activity, respectively. Analyses suggest that these indels affect gene and/or protein function, supporting the in vitro and disease phenotypes. While recombination has been known to occur for C. trachomatis based on gene sequence analyses, we provide the first whole-genome evidence for recombination between a virulent, invasive LGV strain and a noninvasive common urogenital strain. Given the lack of a genetic system for producing stable C. trachomatis mutants, identifying naturally occurring recombinants can clarify gene function and provide opportunities for discovering avenues for genomic manipulation. IMPORTANCE Lymphogranuloma venereum (LGV) is a prevalent and debilitating sexually transmitted disease in developing countries, although there are significant ongoing outbreaks in Australia, Europe, and the United States among men who have sex with men (MSM). Relatively little is known about LGV virulence factors, and only two LGV genomes have been sequenced to date. We isolated an LGV strain from an MSM with severe hemorrhagic proctitis that was morphologically unique in tissue culture compared with other LGV strains. Bioinformatic and statistical analyses identified the strain as a recombinant of L2 and D strains with highly conserved clustered regions of genetic exchange. The unique culture morphology and, more importantly, disease phenotype could be traced to the genes involved in recombination. The findings have implications for bacterial species evolution and, in the case of ongoing LGV outbreaks, suggest that recombination is a mechanism for strain emergence that results in significant disease pathology.
format	article
author	Naraporn Somboonna Raymond Wan David M. Ojcius Matthew A. Pettengill Sandeep J. Joseph Alexander Chang Ray Hsu Timothy D. Read Deborah Dean
author_facet	Naraporn Somboonna Raymond Wan David M. Ojcius Matthew A. Pettengill Sandeep J. Joseph Alexander Chang Ray Hsu Timothy D. Read Deborah Dean
author_sort	Naraporn Somboonna
title	Hypervirulent <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L<sub>2</sub>) and D Lineages
title_short	Hypervirulent <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L<sub>2</sub>) and D Lineages
title_full	Hypervirulent <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L<sub>2</sub>) and D Lineages
title_fullStr	Hypervirulent <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L<sub>2</sub>) and D Lineages
title_full_unstemmed	Hypervirulent <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L<sub>2</sub>) and D Lineages
title_sort	hypervirulent <named-content content-type="genus-species">chlamydia trachomatis</named-content> clinical strain is a recombinant between lymphogranuloma venereum (l<sub>2</sub>) and d lineages
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/514aa54432b64bba83cc363007c38c7c
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Hypervirulent <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L<sub>2</sub>) and D Lineages

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