Acinetobacter baumannii Gastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A
Abstract
Multidrug-resistantAcinetobacter baumanniiis 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 forA. 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 theA. baumanniiclinical isolate Ci79. Surprisingly, SIgA appeared to enhanceA. baumanniiGI 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, atrxAtargeted deletion mutant (ΔtrxA) showed reduced bacterial burdens within the GI tract 24 h after oral challenge byin vivolive 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 theΔtrxAmutant was increased nearly 100-fold in an intraperitoneal sepsis model. These data suggest that TrxA not only mediatesA. baumanniiGI tract colonization but also may contribute to pathogenesis inA. baumanniisepsis following escape from the GI tract under conditions when the intestinal barrier is compromised, as occurs with cases of severe shock and trauma.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 05, 2018
- Source ID
- 10.1128/mbio.01298-18
Entities
People
- Andrew P Cap
- Bernard P Arulanandam
- Holly C. May
- J. Seshu
- James P. Chambers
- Jieh-Juen Yu
- Karl E. Klose
- M. Neal Guentzel
- Mark Eppinger
- Patrick M. Ketter
- Rishein Gupta
Organizations
- United States Department of Defense
- University of Texas at San Antonio