Arginine Is a Critical Substrate for the Pathogenesis ofPseudomonas aeruginosain Burn Wound Infections
Abstract
Environmental conditions affect bacterial behavior and can greatly influence the course of an infection. However, the environmental cues that elicit bacterial responses in specific infection sites are relatively unknown.Pseudomonas aeruginosais ubiquitous in nature and typically innocuous. However, it is also one of the most prevalent causes of fatal sepsis in burn wound patients. The aim of this study was to determine the impact of environmental factors, specifically the availability of arginine, on the pathogenesis ofP. aeruginosain burn wound infections. Comparison of burned versus noninjured tissue revealed thatl-arginine (l-Arg) was significantly depleted in burn wounds as a consequence of elevated arginase produced by myeloid-derived suppressor cells. We also observed thatl-Arg was a potent chemoattractant forP. aeruginosa, and while low concentrations ofl-Arg increasedP. aeruginosa’s swimming motility, high concentrations resulted in diminished swimming. Based on these observations, we tested whether the administration of exogenousl-Arg into the burn wound could attenuate the virulence ofP. aeruginosain thermally injured mice. Administration ofl-Arg resulted in decreasedP. aeruginosaspread and sepsis and increased animal survival. Taken together, these data demonstrate that the availability of environmental arginine greatly influences the virulence ofP. aeruginosa in vivoand may represent a promising phenotype-modulating tool for future therapeutic avenues.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 03, 2017
- Source ID
- 10.1128/mbio.02160-16
Entities
People
- Jake Everett
- Keith Turner
- Kendra Rumbaugh
- Marvin Whiteley
- Qiuxian Cai
- Vernita D. Gordon
Organizations
- Army Research Office
- Monsanto
- National Institute of Allergy and Infectious Diseases
- Texas Tech University Health Sciences Center
- University of Texas at Austin