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2017 ; 8
(2
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Arginine Is a Critical Substrate for the Pathogenesis of Pseudomonas aeruginosa
in Burn Wound Infections
#MMPMID28292986
Everett J
; Turner K
; Cai Q
; Gordon V
; Whiteley M
; Rumbaugh K
mBio
2017[Mar]; 8
(2
): ä PMID28292986
show ga
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.