T3SS and alginate biosynthesis of Pseudomonas aeruginosa impair healing of infected rabbit wounds.

Autor: Karna SLR; Division of Combat Wound Repair, US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX, USA., Nguyen JQ; Division of Combat Wound Repair, US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX, USA., Evani SJ; Division of Combat Wound Repair, US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX, USA., Qian LW; Division of Combat Wound Repair, US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX, USA., Chen P; Division of Combat Wound Repair, US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX, USA., Abercrombie JJ; Division of Combat Wound Repair, US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX, USA., Sebastian EA; Division of Combat Wound Repair, US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX, USA., Fourcaudot AB; Division of Combat Wound Repair, US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX, USA., Leung KP; Division of Combat Wound Repair, US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX, USA. Electronic address: kai.p.leung.civ@mail.mil.
Jazyk: angličtina
Zdroj: Microbial pathogenesis [Microb Pathog] 2020 Oct; Vol. 147, pp. 104254. Date of Electronic Publication: 2020 May 13.
DOI: 10.1016/j.micpath.2020.104254
Abstrakt: Pseudomonas aeruginosa (a Gram-negative bacterium) is an opportunistic pathogen found in many infected wounds and is known to impair healing. To test the hypothesis that knocking out P. aeruginosa genes that are overexpressed during wound infection can cripple a pathogen's ability to impair healing, we assessed two pathways: the Type III secretion system (T3SS) and alginate biosynthesis. We generated single- and double-mutant strains of ExsA (T3SS activator), AlgD (GDP- mannose 6-dehydrogenase of alginate biosynthesis) and their complemented strains and evaluated their pathogenicity in a rabbit ear full-thickness excision-wound infection model. Wounds were inoculated with different strains (wild type, mutants, and complementary strains) at 10 6  CFU/wound on post-wounding day 3. After 24 h, 5 days and 9 days post-infection, wounds were harvested for measuring bacterial counts (viable and total) and wound healing (epithelial gap). On day 9 post-infection, the viable counts of the double mutant, (exsA/algD)‾ were 100-fold lower than the counts of the wild type (PAO1), single mutants, or the complement double-mutant, (exsA/algD)‾ /+ . Also, when compared to wounds infected with wild type or control strains, wounds infected with the double-knockout mutant was less inhibitory to wound healing (p < 0.05). Additionally, the double mutant showed greater susceptibility to macrophage phagocytosis in vitro than all other strains (p < 0.001). In conclusion, compared to single gene knockouts, double knockout of virulence genes in T3SS pathway and alginate biosynthesis pathway is more effective in reducing P. aeruginosa pathogenicity and its ability to impair wound healing. This study highlights the necessity of a dual-targeted anti-virulence strategy to improve healing outcomes of P. aeruginosa-infected wounds.
(Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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