title: 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 that l-arginine (l-Arg) was significantly depleted in burn wounds as a consequence of elevated arginase produced by myeloid-derived suppressor cells. We also observed that l-Arg was a potent chemoattractant forP. aeruginosa, and while low concentrations of l-Arg increasedP. aeruginosa's swimming motility, high concentrations resulted in diminished swimming. Based on these observations, we tested whether the administration of exogenous l-Arg into the burn wound could attenuate the virulence ofP. aeruginosain thermally injured mice. Administration of l-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.IMPORTANCEDespite our growing understanding of the pathophysiology of burn wounds and the evolution of techniques and practices to manage infections, sepsis remains a significant medical concern for burn patients.P. aeruginosacontinues to be a leader among all causes of bacteremic infections due to its tendency to cause complications in immunocompromised patients and its ubiquitous presence in the hospital setting. With the unforgiving emergence of multidrug-resistant strains, it is critical that alternative strategies to control or prevent septic infections in burn patients be developed in parallel with novel antimicrobial agents. In this study, we observed that administration of l-Arg significantly reduced bacterial spread and sepsis in burned mice infected withP. aeruginosaGiven the safety of l-Arg in high doses and its potential wound-healing benefits, this conditionally essential amino acid may represent a useful tool to modulate bacterial behaviorin vivoand prevent sepsis in burn patients.
authors.affiliation: Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
authors.forename: Jake
authors.initials: J
authors.lastname: Everett
authors.affiliation: Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, John Ring LaMontagne Center for Infectious Disease, The University of Texas at Austin, Austin, Texas, USA.|Monsanto Company, Chesterfield, Missouri, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Turner
authors.affiliation: Department of Physics, the University of Texas at Austin, Austin, Texas, USA.
authors.forename: Qiuxian
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Department of Physics, the University of Texas at Austin, Austin, Texas, USA.
authors.forename: Vernita
authors.initials: V
authors.lastname: Gordon
authors.affiliation: Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, John Ring LaMontagne Center for Infectious Disease, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Marvin
authors.initials: M
authors.lastname: Whiteley
authors.affiliation: Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, Texas, USA kendra.rumbaugh@ttuhsc.edu.
authors.forename: Kendra
authors.initials: K
authors.lastname: Rumbaugh
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism; D001120:Arginine / Q000008:administration & dosage / Q000378:metabolism*; D002056:Burns / Q000150:complications*; D004195:Disease Models, Animal; D051379:Mice; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000254:growth & development* / Q000378:metabolism*; D016019:Survival Analysis; D016896:Treatment Outcome; D014774:Virulence; D014946:Wound Infection / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D001120:Arginine