Diverse Requirements for Src-Family Tyrosine Kinases Distinguish Chlamydial Species

ABSTRACT Chlamydiae are well known for their species specificity and tissue tropism, and yet the individual species and strains show remarkable genomic synteny and share an intracellular developmental cycle unique in the microbial world. Only a relatively few chlamydial genes have been linked to spe...

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Autores principales:	Jeffrey Mital, Ted Hackstadt
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/83e6fc850a144c50a2a3d0dcff4cfce6
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spelling	oai:doaj.org-article:83e6fc850a144c50a2a3d0dcff4cfce62021-11-15T15:39:07ZDiverse Requirements for Src-Family Tyrosine Kinases Distinguish Chlamydial Species10.1128/mBio.00031-112150-7511https://doaj.org/article/83e6fc850a144c50a2a3d0dcff4cfce62011-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00031-11https://doaj.org/toc/2150-7511ABSTRACT Chlamydiae are well known for their species specificity and tissue tropism, and yet the individual species and strains show remarkable genomic synteny and share an intracellular developmental cycle unique in the microbial world. Only a relatively few chlamydial genes have been linked to specific disease or tissue tropism. Here we show that chlamydial species associated with human infections, Chlamydia trachomatis and C. pneumoniae, exhibit unique requirements for Src-family kinases throughout their developmental cycle. Utilization of Src-family kinases by C. trachomatis includes tyrosine phosphorylation of the secreted effector Tarp during the entry process, a functional role in microtubule-dependent trafficking to the microtubule organizing center, and a requirement for Src-family kinases for successful initiation of development. Nonhuman chlamydial species C. caviae and C. muridarum show none of these requirements and, instead, appear to be growth restricted by the activities of Src-family kinases. Depletion of Src-family kinases triggers a more rapid development of C. caviae with up to an 800% increase in infectious progeny production. Collectively, the results suggest that human chlamydial species have evolved requirements for tyrosine phosphorylation by Src-family kinases that are not seen in other chlamydial species. The requirement for Src-family kinases thus represents a fundamental distinction between chlamydial species that would not be readily apparent in genomic comparisons and may provide insights into chlamydial disease association and species specificity. IMPORTANCE Chlamydiae are well known for their species specificity and tissue tropism as well as their association with unique diseases. A paradox in the field relates to the remarkable genomic synteny shown among chlamydiae and the very few chlamydial genes linked to specific diseases. We have found that different chlamydial species exhibit unique requirements for Src-family kinases. These differing requirements for Src-family kinases would not be apparent in genomic comparisons and appear to be a previously unrecognized distinction that may provide insights to guide research in chlamydial pathogenesis.Jeffrey MitalTed HackstadtAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 2 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jeffrey Mital Ted Hackstadt Diverse Requirements for Src-Family Tyrosine Kinases Distinguish Chlamydial Species
description	ABSTRACT Chlamydiae are well known for their species specificity and tissue tropism, and yet the individual species and strains show remarkable genomic synteny and share an intracellular developmental cycle unique in the microbial world. Only a relatively few chlamydial genes have been linked to specific disease or tissue tropism. Here we show that chlamydial species associated with human infections, Chlamydia trachomatis and C. pneumoniae, exhibit unique requirements for Src-family kinases throughout their developmental cycle. Utilization of Src-family kinases by C. trachomatis includes tyrosine phosphorylation of the secreted effector Tarp during the entry process, a functional role in microtubule-dependent trafficking to the microtubule organizing center, and a requirement for Src-family kinases for successful initiation of development. Nonhuman chlamydial species C. caviae and C. muridarum show none of these requirements and, instead, appear to be growth restricted by the activities of Src-family kinases. Depletion of Src-family kinases triggers a more rapid development of C. caviae with up to an 800% increase in infectious progeny production. Collectively, the results suggest that human chlamydial species have evolved requirements for tyrosine phosphorylation by Src-family kinases that are not seen in other chlamydial species. The requirement for Src-family kinases thus represents a fundamental distinction between chlamydial species that would not be readily apparent in genomic comparisons and may provide insights into chlamydial disease association and species specificity. IMPORTANCE Chlamydiae are well known for their species specificity and tissue tropism as well as their association with unique diseases. A paradox in the field relates to the remarkable genomic synteny shown among chlamydiae and the very few chlamydial genes linked to specific diseases. We have found that different chlamydial species exhibit unique requirements for Src-family kinases. These differing requirements for Src-family kinases would not be apparent in genomic comparisons and appear to be a previously unrecognized distinction that may provide insights to guide research in chlamydial pathogenesis.
format	article
author	Jeffrey Mital Ted Hackstadt
author_facet	Jeffrey Mital Ted Hackstadt
author_sort	Jeffrey Mital
title	Diverse Requirements for Src-Family Tyrosine Kinases Distinguish Chlamydial Species
title_short	Diverse Requirements for Src-Family Tyrosine Kinases Distinguish Chlamydial Species
title_full	Diverse Requirements for Src-Family Tyrosine Kinases Distinguish Chlamydial Species
title_fullStr	Diverse Requirements for Src-Family Tyrosine Kinases Distinguish Chlamydial Species
title_full_unstemmed	Diverse Requirements for Src-Family Tyrosine Kinases Distinguish Chlamydial Species
title_sort	diverse requirements for src-family tyrosine kinases distinguish chlamydial species
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/83e6fc850a144c50a2a3d0dcff4cfce6
work_keys_str_mv	AT jeffreymital diverserequirementsforsrcfamilytyrosinekinasesdistinguishchlamydialspecies AT tedhackstadt diverserequirementsforsrcfamilytyrosinekinasesdistinguishchlamydialspecies
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Diverse Requirements for Src-Family Tyrosine Kinases Distinguish Chlamydial Species

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