<italic toggle="yes">In Vivo</italic> Transcriptional Profiling of <named-content content-type="genus-species">Yersinia pestis</named-content> Reveals a Novel Bacterial Mediator of Pulmonary Inflammation

ABSTRACT Inhalation of Yersinia pestis results in primary pneumonic plague, a highly lethal and rapidly progressing necrotizing pneumonia. The disease begins with a period of extensive bacterial replication in the absence of disease symptoms, followed by the sudden onset of inflammatory responses th...

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Autores principales:	Roger D. Pechous, Christopher A. Broberg, Nikolas M. Stasulli, Virginia L. Miller, William E. Goldman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/787cf14f7c644f0eb875b5772cf524c4
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spelling	oai:doaj.org-article:787cf14f7c644f0eb875b5772cf524c42021-11-15T15:41:19Z<italic toggle="yes">In Vivo</italic> Transcriptional Profiling of <named-content content-type="genus-species">Yersinia pestis</named-content> Reveals a Novel Bacterial Mediator of Pulmonary Inflammation10.1128/mBio.02302-142150-7511https://doaj.org/article/787cf14f7c644f0eb875b5772cf524c42015-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02302-14https://doaj.org/toc/2150-7511ABSTRACT Inhalation of Yersinia pestis results in primary pneumonic plague, a highly lethal and rapidly progressing necrotizing pneumonia. The disease begins with a period of extensive bacterial replication in the absence of disease symptoms, followed by the sudden onset of inflammatory responses that ultimately prove fatal. Very little is known about the bacterial and host factors that contribute to the rapid biphasic progression of pneumonic plague. In this work, we analyzed the in vivo transcription kinetics of 288 bacterial open reading frames previously shown by microarray analysis to be dynamically regulated in the lung. Using this approach combined with bacterial genetics, we were able to identify five Y. pestis genes that contribute to the development of pneumonic plague. Deletion of one of these genes, ybtX, did not alter bacterial survival but attenuated host inflammatory responses during late-stage disease. Deletion of ybtX in another lethal respiratory pathogen, Klebsiella pneumoniae, also resulted in diminished host inflammation during infection. Thus, our in vivo transcriptional screen has identified an important inflammatory mediator that is common to two Gram-negative bacterial pathogens that cause severe pneumonia. IMPORTANCE Yersinia pestis is responsible for at least three major pandemics, most notably the Black Death of the Middle Ages. Due to its pandemic potential, ease of dissemination by aerosolization, and a history of its weaponization, Y. pestis is categorized by the Centers for Disease Control and Prevention as a tier 1 select agent most likely to be used as a biological weapon. To date, there is no licensed vaccine against Y. pestis. Importantly, an early “silent” phase followed by the rapid onset of nondescript influenza-like symptoms makes timely treatment of pneumonic plague difficult. A more detailed understanding of the bacterial and host factors that contribute to pathogenesis is essential to understanding the progression of pneumonic plague and developing or enhancing treatment options.Roger D. PechousChristopher A. BrobergNikolas M. StasulliVirginia L. MillerWilliam E. GoldmanAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 1 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Roger D. Pechous Christopher A. Broberg Nikolas M. Stasulli Virginia L. Miller William E. Goldman <italic toggle="yes">In Vivo</italic> Transcriptional Profiling of <named-content content-type="genus-species">Yersinia pestis</named-content> Reveals a Novel Bacterial Mediator of Pulmonary Inflammation
description	ABSTRACT Inhalation of Yersinia pestis results in primary pneumonic plague, a highly lethal and rapidly progressing necrotizing pneumonia. The disease begins with a period of extensive bacterial replication in the absence of disease symptoms, followed by the sudden onset of inflammatory responses that ultimately prove fatal. Very little is known about the bacterial and host factors that contribute to the rapid biphasic progression of pneumonic plague. In this work, we analyzed the in vivo transcription kinetics of 288 bacterial open reading frames previously shown by microarray analysis to be dynamically regulated in the lung. Using this approach combined with bacterial genetics, we were able to identify five Y. pestis genes that contribute to the development of pneumonic plague. Deletion of one of these genes, ybtX, did not alter bacterial survival but attenuated host inflammatory responses during late-stage disease. Deletion of ybtX in another lethal respiratory pathogen, Klebsiella pneumoniae, also resulted in diminished host inflammation during infection. Thus, our in vivo transcriptional screen has identified an important inflammatory mediator that is common to two Gram-negative bacterial pathogens that cause severe pneumonia. IMPORTANCE Yersinia pestis is responsible for at least three major pandemics, most notably the Black Death of the Middle Ages. Due to its pandemic potential, ease of dissemination by aerosolization, and a history of its weaponization, Y. pestis is categorized by the Centers for Disease Control and Prevention as a tier 1 select agent most likely to be used as a biological weapon. To date, there is no licensed vaccine against Y. pestis. Importantly, an early “silent” phase followed by the rapid onset of nondescript influenza-like symptoms makes timely treatment of pneumonic plague difficult. A more detailed understanding of the bacterial and host factors that contribute to pathogenesis is essential to understanding the progression of pneumonic plague and developing or enhancing treatment options.
format	article
author	Roger D. Pechous Christopher A. Broberg Nikolas M. Stasulli Virginia L. Miller William E. Goldman
author_facet	Roger D. Pechous Christopher A. Broberg Nikolas M. Stasulli Virginia L. Miller William E. Goldman
author_sort	Roger D. Pechous
title	<italic toggle="yes">In Vivo</italic> Transcriptional Profiling of <named-content content-type="genus-species">Yersinia pestis</named-content> Reveals a Novel Bacterial Mediator of Pulmonary Inflammation
title_short	<italic toggle="yes">In Vivo</italic> Transcriptional Profiling of <named-content content-type="genus-species">Yersinia pestis</named-content> Reveals a Novel Bacterial Mediator of Pulmonary Inflammation
title_full	<italic toggle="yes">In Vivo</italic> Transcriptional Profiling of <named-content content-type="genus-species">Yersinia pestis</named-content> Reveals a Novel Bacterial Mediator of Pulmonary Inflammation
title_fullStr	<italic toggle="yes">In Vivo</italic> Transcriptional Profiling of <named-content content-type="genus-species">Yersinia pestis</named-content> Reveals a Novel Bacterial Mediator of Pulmonary Inflammation
title_full_unstemmed	<italic toggle="yes">In Vivo</italic> Transcriptional Profiling of <named-content content-type="genus-species">Yersinia pestis</named-content> Reveals a Novel Bacterial Mediator of Pulmonary Inflammation
title_sort	<italic toggle="yes">in vivo</italic> transcriptional profiling of <named-content content-type="genus-species">yersinia pestis</named-content> reveals a novel bacterial mediator of pulmonary inflammation
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/787cf14f7c644f0eb875b5772cf524c4
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<italic toggle="yes">In Vivo</italic> Transcriptional Profiling of <named-content content-type="genus-species">Yersinia pestis</named-content> Reveals a Novel Bacterial Mediator of Pulmonary Inflammation

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