<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Gastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A

ABSTRACT Multidrug-resistant Acinetobacter baumannii is among the most common causes of infectious complications associated with combat-related trauma in military personnel serving overseas. However, little is currently known about its pathogenesis. While the gastrointestinal (GI) tract has been fou...

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Autores principales:	Patrick M. Ketter, Jieh-Juen Yu, M. Neal Guentzel, Holly C. May, Rishein Gupta, Mark Eppinger, Karl E. Klose, J. Seshu, James P. Chambers, Andrew P. Cap, Bernard P. Arulanandam
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Acinetobacter bacterial virulence gastrointestinal infection SIgA thioredoxin Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7480d67b7fd14314a565b9db129cb4d8
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spelling	oai:doaj.org-article:7480d67b7fd14314a565b9db129cb4d82021-11-15T16:00:14Z<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Gastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A10.1128/mBio.01298-182150-7511https://doaj.org/article/7480d67b7fd14314a565b9db129cb4d82018-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01298-18https://doaj.org/toc/2150-7511ABSTRACT Multidrug-resistant Acinetobacter baumannii is among the most common causes of infectious complications associated with combat-related trauma in military personnel serving overseas. However, little is currently known about its pathogenesis. While the gastrointestinal (GI) tract has been found to be a major reservoir for A. baumannii, as well as to potentially contribute to development of multidrug resistance, no studies have addressed the mechanisms involved in gut colonization. In this study, we address this critical gap in knowledge by first assessing the interaction between secretory IgA (SIgA), the principal humoral immune defense on mucosal surfaces, and the A. baumannii clinical isolate Ci79. Surprisingly, SIgA appeared to enhance A. baumannii GI tract colonization, in a process mediated by bacterial thioredoxin A (TrxA), as evidenced by reduction of bacterial attachment in the presence of TrxA inhibitors. Additionally, a trxA targeted deletion mutant (ΔtrxA) showed reduced bacterial burdens within the GI tract 24 h after oral challenge by in vivo live imaging, along with loss of thiol-reductase activity. Surprisingly, not only was GI tract colonization greatly reduced but the associated 50% lethal dose (LD50) of the ΔtrxA mutant was increased nearly 100-fold in an intraperitoneal sepsis model. These data suggest that TrxA not only mediates A. baumannii GI tract colonization but also may contribute to pathogenesis in A. baumannii sepsis following escape from the GI tract under conditions when the intestinal barrier is compromised, as occurs with cases of severe shock and trauma. IMPORTANCE Acinetobacter baumannii is an emerging bacterial pathogen recently classified as a serious threat to U.S. and global health by both the Centers for Disease Control and Prevention and the World Health Organization. It also is one of the leading causes of combat-related infections associated with injured military personnel serving overseas. Little is known regarding mechanisms of gastrointestinal tract colonization despite this site being shown to serve as a reservoir for multidrug-resistant (MDR) A. baumannii isolates. Here, we establish that secretory IgA, the major immunoglobulin of mucosal surfaces, promotes A. baumannii GI tract colonization via bacterial thioredoxin A as evidenced through significant reduction in colonization in IgA-deficient animals. Additionally, bacterial colonization and mortality were significantly reduced in animals challenged with a thioredoxin A-deficient A. baumannii mutant. Combined, these data suggest that thioredoxin A is a novel virulence factor, for which antithioredoxin therapies could be developed, for this important multidrug-resistant pathogen.Patrick M. KetterJieh-Juen YuM. Neal GuentzelHolly C. MayRishein GuptaMark EppingerKarl E. KloseJ. SeshuJames P. ChambersAndrew P. CapBernard P. ArulanandamAmerican Society for MicrobiologyarticleAcinetobacterbacterial virulencegastrointestinal infectionSIgAthioredoxinMicrobiologyQR1-502ENmBio, Vol 9, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Acinetobacter bacterial virulence gastrointestinal infection SIgA thioredoxin Microbiology QR1-502
spellingShingle	Acinetobacter bacterial virulence gastrointestinal infection SIgA thioredoxin Microbiology QR1-502 Patrick M. Ketter Jieh-Juen Yu M. Neal Guentzel Holly C. May Rishein Gupta Mark Eppinger Karl E. Klose J. Seshu James P. Chambers Andrew P. Cap Bernard P. Arulanandam <named-content content-type="genus-species">Acinetobacter baumannii</named-content> Gastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A
description	ABSTRACT Multidrug-resistant Acinetobacter baumannii is among the most common causes of infectious complications associated with combat-related trauma in military personnel serving overseas. However, little is currently known about its pathogenesis. While the gastrointestinal (GI) tract has been found to be a major reservoir for A. baumannii, as well as to potentially contribute to development of multidrug resistance, no studies have addressed the mechanisms involved in gut colonization. In this study, we address this critical gap in knowledge by first assessing the interaction between secretory IgA (SIgA), the principal humoral immune defense on mucosal surfaces, and the A. baumannii clinical isolate Ci79. Surprisingly, SIgA appeared to enhance A. baumannii GI tract colonization, in a process mediated by bacterial thioredoxin A (TrxA), as evidenced by reduction of bacterial attachment in the presence of TrxA inhibitors. Additionally, a trxA targeted deletion mutant (ΔtrxA) showed reduced bacterial burdens within the GI tract 24 h after oral challenge by in vivo live imaging, along with loss of thiol-reductase activity. Surprisingly, not only was GI tract colonization greatly reduced but the associated 50% lethal dose (LD50) of the ΔtrxA mutant was increased nearly 100-fold in an intraperitoneal sepsis model. These data suggest that TrxA not only mediates A. baumannii GI tract colonization but also may contribute to pathogenesis in A. baumannii sepsis following escape from the GI tract under conditions when the intestinal barrier is compromised, as occurs with cases of severe shock and trauma. IMPORTANCE Acinetobacter baumannii is an emerging bacterial pathogen recently classified as a serious threat to U.S. and global health by both the Centers for Disease Control and Prevention and the World Health Organization. It also is one of the leading causes of combat-related infections associated with injured military personnel serving overseas. Little is known regarding mechanisms of gastrointestinal tract colonization despite this site being shown to serve as a reservoir for multidrug-resistant (MDR) A. baumannii isolates. Here, we establish that secretory IgA, the major immunoglobulin of mucosal surfaces, promotes A. baumannii GI tract colonization via bacterial thioredoxin A as evidenced through significant reduction in colonization in IgA-deficient animals. Additionally, bacterial colonization and mortality were significantly reduced in animals challenged with a thioredoxin A-deficient A. baumannii mutant. Combined, these data suggest that thioredoxin A is a novel virulence factor, for which antithioredoxin therapies could be developed, for this important multidrug-resistant pathogen.
format	article
author	Patrick M. Ketter Jieh-Juen Yu M. Neal Guentzel Holly C. May Rishein Gupta Mark Eppinger Karl E. Klose J. Seshu James P. Chambers Andrew P. Cap Bernard P. Arulanandam
author_facet	Patrick M. Ketter Jieh-Juen Yu M. Neal Guentzel Holly C. May Rishein Gupta Mark Eppinger Karl E. Klose J. Seshu James P. Chambers Andrew P. Cap Bernard P. Arulanandam
author_sort	Patrick M. Ketter
title	<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Gastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A
title_short	<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Gastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A
title_full	<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Gastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A
title_fullStr	<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Gastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A
title_full_unstemmed	<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Gastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A
title_sort	<named-content content-type="genus-species">acinetobacter baumannii</named-content> gastrointestinal colonization is facilitated by secretory iga which is reductively dissociated by bacterial thioredoxin a
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/7480d67b7fd14314a565b9db129cb4d8
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<named-content content-type="genus-species">Acinetobacter baumannii</named-content> Gastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A

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