Increased susceptibility to lethal Candida infections in burned mice preinfected with Pseudomonas aeruginosa or pretreated with proteolytic enzymes

Abstract

Lethal Candida infections in burn patients are frequently preceded by or occur concomitantly with bacterial infections, which are often due to Pseudomonas aeruginosa. In this study, we developed a burned, mixed-challenge mouse model, which was designed to determine whether and how a recent bacterial infection could influence the development of subsequent candidosis. In this model, burned mice that were preinfected with a sublethal challenge of elastase-producing P. aeruginosa strain WR-5 and then sublethally challenged with Candida albicans exhibited a mortality rate of 60%, while unburned mice challenged in the same way and burned mice that received only one challenge organism exhibited mortality rates of <10%. Quantitative microbial counts performed with the kidneys, livers, and eschars of burned mice challenged with both organisms indicated that the deaths were due to Candida infection. Substitution of an elastase-negative P. aeruginosa strain for strain WR-5 in the model resulted in significantly lower mortality rates and lower microbial numbers in the organs. When the Pseudomonas enzyme elastase was substituted for the elastasepositive bacteria in the model, both the mortality rates and the organ counts were comparable to the values found after preinfection with strain WR-5. Another protease, thermolysin, was substituted for the elastase and produced similar mortality results. When the protease inhibitor a2-macroglobulin was given to burned mice infected with the two organisms, it prevented the deaths due to Candida infection. We concluded that this model is one way to study bacterial-fungal infections in burned mice, that recent Pseudomonas infections could predispose burned mice to fatal candidosis, and that the proteolytic activity generated by the bacteria was primarily responsible for the establishment of lethal fungal infections.

Anticandidal activity of Pseudomonas aeruginosa strains isolated from clinical specimens

“…This agrees with the findings of earlier studies. 14,18,19 Gupta et al [18] determined 59% Candida species in cases with bacteria infected burn wounds. However, when P. aeruginosa was present, fungal colonisation was significantly inhibited.…”

Candida albicansandEnterococcus faecalisin the gut

“…25 The presence of Pseudomonas exacerbates tissue damage in a model of Candida infection of burn wounds. 26 Biofilms formed between C. albicans and either S. aureus or S. gordonii are larger and more drug resistant than their monomicrobial counterparts. 24,27 Clearly there are context-dependent interactions that prevent simple conclusions about the in vivo effect of mixed infections.…”

Inactivation of human gamma interferon by Pseudomonas aeruginosa proteases: elastase augments the effects of alkaline protease despite the presence of alpha 2-macroglobulin

“…Patients infected with P. aeruginosa often show evidence of impaired cell-mediated immunity (28,33,34). In support of these clinical findings, Neely et al (25) demonstrated that infection with P. aeruginosa predisposed burned mice to lethal infections with Candida albicans. Two independent groups, Blackwood et al (5) and Petit et al (30), found that mice injected with P. aeruginosa were more susceptible to infection with the intracellular pathogen Listeria monocytogenes and showed a decrease in delayed-type hypersensitivity to Listeria and erythrocyte antigens.…”