Arginine Is a Critical Substrate for the Pathogenesis of <italic toggle="yes">Pseudomonas aeruginosa</italic> in 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 aeruginosa is ubiquitous in nature and typically innocuous...

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Autores principales:	Jake Everett, Keith Turner, Qiuxian Cai, Vernita Gordon, Marvin Whiteley, Kendra Rumbaugh
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bb02bf42a41e47bea4e8c285322f7254
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spelling	oai:doaj.org-article:bb02bf42a41e47bea4e8c285322f72542021-11-15T15:50:59ZArginine Is a Critical Substrate for the Pathogenesis of <italic toggle="yes">Pseudomonas aeruginosa</italic> in Burn Wound Infections10.1128/mBio.02160-162150-7511https://doaj.org/article/bb02bf42a41e47bea4e8c285322f72542017-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02160-16https://doaj.org/toc/2150-7511ABSTRACT 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 aeruginosa is 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 of P. aeruginosa in 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 for P. aeruginosa, and while low concentrations of l-Arg increased P. 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 of P. aeruginosa in thermally injured mice. Administration of l-Arg resulted in decreased P. aeruginosa spread and sepsis and increased animal survival. Taken together, these data demonstrate that the availability of environmental arginine greatly influences the virulence of P. aeruginosa in vivo and may represent a promising phenotype-modulating tool for future therapeutic avenues. IMPORTANCE Despite 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. aeruginosa continues 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 with P. aeruginosa. Given 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 behavior in vivo and prevent sepsis in burn patients.Jake EverettKeith TurnerQiuxian CaiVernita GordonMarvin WhiteleyKendra RumbaughAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 8, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jake Everett Keith Turner Qiuxian Cai Vernita Gordon Marvin Whiteley Kendra Rumbaugh Arginine Is a Critical Substrate for the Pathogenesis of <italic toggle="yes">Pseudomonas aeruginosa</italic> in Burn Wound Infections
description	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 aeruginosa is 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 of P. aeruginosa in 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 for P. aeruginosa, and while low concentrations of l-Arg increased P. 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 of P. aeruginosa in thermally injured mice. Administration of l-Arg resulted in decreased P. aeruginosa spread and sepsis and increased animal survival. Taken together, these data demonstrate that the availability of environmental arginine greatly influences the virulence of P. aeruginosa in vivo and may represent a promising phenotype-modulating tool for future therapeutic avenues. IMPORTANCE Despite 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. aeruginosa continues 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 with P. aeruginosa. Given 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 behavior in vivo and prevent sepsis in burn patients.
format	article
author	Jake Everett Keith Turner Qiuxian Cai Vernita Gordon Marvin Whiteley Kendra Rumbaugh
author_facet	Jake Everett Keith Turner Qiuxian Cai Vernita Gordon Marvin Whiteley Kendra Rumbaugh
author_sort	Jake Everett
title	Arginine Is a Critical Substrate for the Pathogenesis of <italic toggle="yes">Pseudomonas aeruginosa</italic> in Burn Wound Infections
title_short	Arginine Is a Critical Substrate for the Pathogenesis of <italic toggle="yes">Pseudomonas aeruginosa</italic> in Burn Wound Infections
title_full	Arginine Is a Critical Substrate for the Pathogenesis of <italic toggle="yes">Pseudomonas aeruginosa</italic> in Burn Wound Infections
title_fullStr	Arginine Is a Critical Substrate for the Pathogenesis of <italic toggle="yes">Pseudomonas aeruginosa</italic> in Burn Wound Infections
title_full_unstemmed	Arginine Is a Critical Substrate for the Pathogenesis of <italic toggle="yes">Pseudomonas aeruginosa</italic> in Burn Wound Infections
title_sort	arginine is a critical substrate for the pathogenesis of <italic toggle="yes">pseudomonas aeruginosa</italic> in burn wound infections
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/bb02bf42a41e47bea4e8c285322f7254
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Arginine Is a Critical Substrate for the Pathogenesis of <italic toggle="yes">Pseudomonas aeruginosa</italic> in Burn Wound Infections

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