Prostaglandin E2 production by high and low virulent strains of Paracoccidioides brasiliensis

Abstract

The production of prostaglandins (PGs) during fungal infections could be an important suppressor factor of host immune response. Host cells are one source of prostaglandin E(2) (PGE(2)); however another potential source of PGE(2) is the fungal pathogen itself. Thus, both host and fungal PGE2 production is theorized to play a role in pathogenesis, being critical for growth of the fungus and to modulate the host immune response. The purpose of this work was to investigate if high and low virulent strains of Paracoccidioides brasiliensis have the capacity to produce PGE(2) in vitro, and if this production was related to the fungal growth. The results demonstrated that both strains of P. brasiliensis produce high levels of PGE(2) and the treatment with indomethacin, a cyclooxygenase inhibitor, significantly reduced the production of this mediator, as well as the viability of the fungus. Thus, our data indicate that PGE(2) is produced by P. brasiliensis by a cyclooxygenase-dependent metabolic pathway, and its production is required for fungal survival. This discovery reveals an important factor that has potentially great implications for understanding the mechanisms of immune deviation during infection.

Antifungal activity of some cyclooxygenase inhibitors on Candida albicans: PGE2-dependent mechanism

“…These data are consistent with our result that PGE2 completely reversed the inhibitory effect of indomethacin on the growth of C. albicans (Table 1). In addition, a study also showed that incubation of Paracoccidioides brasiliensis cultures with indomethacin significantly inhibited the production of PGE2 and fungal viability (Bordon et al 2007), which supports the hypothesis that a COXdependent pathway is involved in PGE2 production. Alem and Douglas (2004) showed that aspirin also inhibits up to 95% of biofilm formation by C. albicans, but prostaglandins diminished this inhibitory effect.…”

Production of cross-kingdom oxylipins by pathogenic fungi: An update on their role in development and pathogenicity

“…Since then, prostaglandins have been identified in C. neoformans , several pathogenic species of Candida, P. brasiliensis , and several Aspergillus spp. (Noverr et al ., 2002; Tsitsigiannis et al ., 2005a; Bordon et al ., 2007; Biondo et al ., 2010). …”

Arachidonic acid metabolites in pathogenic yeasts

“…The pathogenic dimorphic yeast, Paracoccidioides brasiliensis , also produced prostaglandins from endogenous and exogenous AA [31,32]. The use of COX inhibitors, indomethacin and piroxicam, not only decreased prostaglandin production but also viability of the yeast.…”