Acinetobacter baumannii Gastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A
- Univ. of Texas at San Antonio, TX (United States). Dept. of Biology
- Univ. of Texas at San Antonio, TX (United States). Dept. of Biology; Univ. of Texas at San Antonio, TX (United States). South Texas Center for Emerging Infectious Disease
- US Army Inst. for Surgical Research, JBSA Fort Sam Houston, TX (United States). Coagulation and Blood Research Program
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.
- Research Organization:
- Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- Grant/Contract Number:
- SC0014664
- OSTI ID:
- 1626130
- Journal Information:
- mBio (Online), Vol. 9, Issue 4; ISSN 2150-7511
- Publisher:
- American Society for Microbiology (ASM)Copyright Statement
- Country of Publication:
- United States
- Language:
- English
Thioredoxin-A is a virulence factor and mediator of the type IV pilus system in Acinetobacter baumannii
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journal | July 2019 |
Thioredoxin Modulates Cell Surface Hydrophobicity in Acinetobacter baumannii
|
journal | December 2019 |
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