Within-Host Evolution of <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> over a Twelve-Year Chronic Carriage Infection

ABSTRACT Burkholderia pseudomallei causes the potentially fatal disease melioidosis. It is generally accepted that B. pseudomallei is a noncommensal bacterium and that any culture-positive clinical specimen denotes disease requiring treatment. Over a 23-year study of melioidosis cases in Darwin, Aus...

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Autores principales:	Erin P. Price, Derek S. Sarovich, Mark Mayo, Apichai Tuanyok, Kevin P. Drees, Mirjam Kaestli, Stephen M. Beckstrom-Sternberg, James S. Babic-Sternberg, Timothy J. Kidd, Scott C. Bell, Paul Keim, Talima Pearson, Bart J. Currie
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/cfdb219ce0154a06888c9456c19f2cc1
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spelling	oai:doaj.org-article:cfdb219ce0154a06888c9456c19f2cc12021-11-15T15:43:08ZWithin-Host Evolution of <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> over a Twelve-Year Chronic Carriage Infection10.1128/mBio.00388-132150-7511https://doaj.org/article/cfdb219ce0154a06888c9456c19f2cc12013-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00388-13https://doaj.org/toc/2150-7511ABSTRACT Burkholderia pseudomallei causes the potentially fatal disease melioidosis. It is generally accepted that B. pseudomallei is a noncommensal bacterium and that any culture-positive clinical specimen denotes disease requiring treatment. Over a 23-year study of melioidosis cases in Darwin, Australia, just one patient from 707 survivors has developed persistent asymptomatic B. pseudomallei carriage. To better understand the mechanisms behind this unique scenario, we performed whole-genome analysis of two strains isolated 139 months apart. During this period, B. pseudomallei underwent several adaptive changes. Of 23 point mutations, 78% were nonsynonymous and 43% were predicted to be deleterious to gene function, demonstrating a strong propensity for positive selection. Notably, a nonsense mutation inactivated the universal stress response sigma factor RpoS, with pleiotropic implications. The genome underwent substantial reduction, with four deletions in chromosome 2 resulting in the loss of 221 genes. The deleted loci included genes involved in secondary metabolism, environmental survival, and pathogenesis. Of 14 indels, 11 occurred in coding regions and 9 resulted in frameshift mutations that dramatically affected predicted gene products. Disproportionately, four indels affected lipopolysaccharide biosynthesis and modification. Finally, we identified a frameshift mutation in both P314 isolates within wcbR, an important component of the capsular polysaccharide I locus, suggesting virulence attenuation early in infection. Our study illustrates a unique clinical case that contrasts a high-consequence infectious agent with a long-term commensal infection and provides further insights into bacterial evolution within the human host. IMPORTANCE Some bacterial pathogens establish long-term infections that are difficult or impossible to eradicate with current treatments. Rapid advances in genome sequencing technologies provide a powerful tool for understanding bacterial persistence within the human host. Burkholderia pseudomallei is considered a highly pathogenic bacterium because infection is commonly fatal. Here, we document within-host evolution of B. pseudomallei in a unique case of human infection with ongoing chronic carriage. Genomic comparison of isolates obtained 139 months (11.5 years) apart showed a strong signal of adaptation within the human host, including inactivation of virulence and immunogenic factors, and deletion of pathways involved in environmental survival. Two global regulatory genes were mutated in the 139-month isolate, indicating extensive regulatory changes favoring bacterial persistence. Our study provides insights into B. pseudomallei pathogenesis and, more broadly, identifies parallel evolutionary mechanisms that underlie chronic persistence of all bacterial pathogens.Erin P. PriceDerek S. SarovichMark MayoApichai TuanyokKevin P. DreesMirjam KaestliStephen M. Beckstrom-SternbergJames S. Babic-SternbergTimothy J. KiddScott C. BellPaul KeimTalima PearsonBart J. CurrieAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 4 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Erin P. Price Derek S. Sarovich Mark Mayo Apichai Tuanyok Kevin P. Drees Mirjam Kaestli Stephen M. Beckstrom-Sternberg James S. Babic-Sternberg Timothy J. Kidd Scott C. Bell Paul Keim Talima Pearson Bart J. Currie Within-Host Evolution of <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> over a Twelve-Year Chronic Carriage Infection
description	ABSTRACT Burkholderia pseudomallei causes the potentially fatal disease melioidosis. It is generally accepted that B. pseudomallei is a noncommensal bacterium and that any culture-positive clinical specimen denotes disease requiring treatment. Over a 23-year study of melioidosis cases in Darwin, Australia, just one patient from 707 survivors has developed persistent asymptomatic B. pseudomallei carriage. To better understand the mechanisms behind this unique scenario, we performed whole-genome analysis of two strains isolated 139 months apart. During this period, B. pseudomallei underwent several adaptive changes. Of 23 point mutations, 78% were nonsynonymous and 43% were predicted to be deleterious to gene function, demonstrating a strong propensity for positive selection. Notably, a nonsense mutation inactivated the universal stress response sigma factor RpoS, with pleiotropic implications. The genome underwent substantial reduction, with four deletions in chromosome 2 resulting in the loss of 221 genes. The deleted loci included genes involved in secondary metabolism, environmental survival, and pathogenesis. Of 14 indels, 11 occurred in coding regions and 9 resulted in frameshift mutations that dramatically affected predicted gene products. Disproportionately, four indels affected lipopolysaccharide biosynthesis and modification. Finally, we identified a frameshift mutation in both P314 isolates within wcbR, an important component of the capsular polysaccharide I locus, suggesting virulence attenuation early in infection. Our study illustrates a unique clinical case that contrasts a high-consequence infectious agent with a long-term commensal infection and provides further insights into bacterial evolution within the human host. IMPORTANCE Some bacterial pathogens establish long-term infections that are difficult or impossible to eradicate with current treatments. Rapid advances in genome sequencing technologies provide a powerful tool for understanding bacterial persistence within the human host. Burkholderia pseudomallei is considered a highly pathogenic bacterium because infection is commonly fatal. Here, we document within-host evolution of B. pseudomallei in a unique case of human infection with ongoing chronic carriage. Genomic comparison of isolates obtained 139 months (11.5 years) apart showed a strong signal of adaptation within the human host, including inactivation of virulence and immunogenic factors, and deletion of pathways involved in environmental survival. Two global regulatory genes were mutated in the 139-month isolate, indicating extensive regulatory changes favoring bacterial persistence. Our study provides insights into B. pseudomallei pathogenesis and, more broadly, identifies parallel evolutionary mechanisms that underlie chronic persistence of all bacterial pathogens.
format	article
author	Erin P. Price Derek S. Sarovich Mark Mayo Apichai Tuanyok Kevin P. Drees Mirjam Kaestli Stephen M. Beckstrom-Sternberg James S. Babic-Sternberg Timothy J. Kidd Scott C. Bell Paul Keim Talima Pearson Bart J. Currie
author_facet	Erin P. Price Derek S. Sarovich Mark Mayo Apichai Tuanyok Kevin P. Drees Mirjam Kaestli Stephen M. Beckstrom-Sternberg James S. Babic-Sternberg Timothy J. Kidd Scott C. Bell Paul Keim Talima Pearson Bart J. Currie
author_sort	Erin P. Price
title	Within-Host Evolution of <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> over a Twelve-Year Chronic Carriage Infection
title_short	Within-Host Evolution of <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> over a Twelve-Year Chronic Carriage Infection
title_full	Within-Host Evolution of <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> over a Twelve-Year Chronic Carriage Infection
title_fullStr	Within-Host Evolution of <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> over a Twelve-Year Chronic Carriage Infection
title_full_unstemmed	Within-Host Evolution of <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> over a Twelve-Year Chronic Carriage Infection
title_sort	within-host evolution of <named-content content-type="genus-species">burkholderia pseudomallei</named-content> over a twelve-year chronic carriage infection
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/cfdb219ce0154a06888c9456c19f2cc1
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Within-Host Evolution of <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> over a Twelve-Year Chronic Carriage Infection

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