4.4 Article

The impact of simultaneous inoculation of Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans on rodent burn wounds

Journal

BURNS
Volume 47, Issue 8, Pages 1818-1832

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.burns.2021.02.025

Keywords

Pseudomonas aeruginosa; Staphylococcus aureus; Candida albicans; Biofilm; Damage-associated molecular patterns; Walker-Mason rat burn model

Funding

  1. Naval Medical Research Center's Advanced Medical Development Program [MIPR N3239815MHX040]
  2. Combat Casualty Care Research Directorate, U.S. Army Medical Research and Development Command (USAMRDC) [G_001-2016-USAISR]
  3. U.S. Department of Energy
  4. USAMRDC

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This study characterized mixed species burn wound infections by inoculating burn surfaces with Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans. The presence of biofilms from these pathogens in the wound led to burn depth progression, increased release of inflammatory mediators, and elevated circulating immune cells. The findings provide insights for developing new antimicrobials targeting biofilm-based wound infections.
Burn wound infection often involves a diverse combination of bacterial and fungal pathogens. In this study, we characterize the mixed species burn wound infection by inoculating the burn surface with 1 x 10(3/4/5) CFU of Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans in a 1:1:1 ratio. Using the revised Walker-Mason scald burn rat model, 168 male Sprague-Dawley rats (350-450 g) subject to similar to 10% TBSA burn injury, with or without inoculation, were evaluated for 11 days after burn. In the wound, P. aeruginosa and S. aureus formed robust biofilms as determined by the bacterial tissue load, similar to 1 x 10(9) CFU/g, and expression of key biofilm genes. Interestingly, within 3 days C. albicans achieved tissue loads of similar to 1 x 10(6) CFU/g, but its numbers were significantly reduced beyond the limit of detection in the burn wound by day 7 in partial-thickness injuries and by day 11 in full-thickness injuries. The pathogenic biofilms contributed to burn depth progression, increased release of HMGB-1 into circulation from injured tissue, and significantly elevated the numbers of circulating innate immune cells (Neutrophils, Monocytes, and Basophils). This robust model of multispecies burn wound infection will serve as the basis for the development of new antimicrobials for combating biofilm-based wound infections. Published by Elsevier Ltd.

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