Arachidonic acid affects biofilm formation and PGE2 level in Candida albicans and non-albicans species in presence of subinhibitory concentration of fluconazole and terbinafine

Abstract

Candida albicans utilizes arachidonic acid (AA) released during the course of infection (Candidiasis) from phospholipids of infected host cell membranes and synthesizes extracellular prostaglandin(s) which play an important role in hyphae formation and host cell damage. C. albicans biofilms secrete significantly more prostaglandin(s) and evidence suggests that Candida biofilms have dramatically reduced susceptibility to majority of antifungal drugs. AA influences the saturation level of lipids and fluidity of yeast cell membranes. Therefore the aim of this study was to evaluate the effect of AA alone or in combination with antifungal agents on biofilm formation and production of prostaglandin (PGE2) in C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, and C. albicans amphotericin B resistant strain (AmBR). Maximum biofilm formation was found to be in the case of C. albicans compared to C. non-albicans species. However, among the non-albicans species C. tropicalis exhibited highest biofilm formation. Treatment with AA in combination with subinhibitory concentrations of fluconazole and terbinafine separately exhibited significant (p<0.05) reduction in biofilm formation against C. glabrata, C. parapsilosis, C. tropicalis and AmBR as compared to their individual effect. Further, these two antifungal agents in combination with AA caused an increase in production of prostaglandin from fungal cell itself which was significant (p<0.05) in case of all the strains tested.

Potential Antifungal Targets against a Candida Biofilm Based on an Enzyme in the Arachidonic Acid Cascade—A Review

“…So enhancing PGE 2 level during fungal infections can aggravate fungal colonization in biofilm formation and trigger chronic infection (Noverr et al, 2001). Evidence reveals that candidiasis is associated with high levels of PGE 2 (Noverr et al, 2003), and decreased prostaglandin production during C. albican infections is an important factor in relieving chronic infections (Mishra et al, 2014). In addition, research suggests that PGE 2 is produced in both C. albicans planktonic and biofilm cells (Ells et al, 2011), while biofilm cells secreted significantly more PGE 2 than the planktonic cells when determined according to cell dry weight.…”

“…According to Erb-Downward's research, fatty acid desaturase homolog (Ole2p) and multicopper oxidase homolog (Fet3p) are necessary enzymes that participate in PGE 2 biosynthesis in C. albicans (Erb-Downward and Noverr, 2007), while the role of OLE2 in C. parapsilosis is relatively weaker, it is able to decrease C. parapsilosis virulence, but is dispensable for PGE 2 synthesis (Grozer et al, 2015). Furthermore, PGE 2 production is a significant virulence factor in biofilm-associated infections of C. albicans and non-albicans species (Mishra et al, 2014), the relative lower virulence of C. dubliniensis compared to C. albicans may be contributed to its lower PGE 2 level (Ells et al, 2011). The role of PGE 2 in polymicrobial infection has also been studied.…”

“…Recent research has revealed that PGE 2 is produced by human eukaryotic cells as well as by pathogenic fungi (Noverr et al, 2001, 2002). AA in combination with antifungal agents can affect PGE 2 levels in several Candida species (Mishra et al, 2014). Some studies have suggested that fungal prostaglandin can act as a regulator for biofilm development in C. albicans and that it is also a significant virulence factor in biofilm-associated infections of C. albicans (Alem and Douglas, 2005).…”

Effect of non-steroidal anti-inflammatory drugs and dexamethazone on the biofilm formation and expression of some adhesion-related genes of Candida albicans and Staphylococcus aureus

“…Dexamethazone cause the repression of COX2 and prostaglandin E2 release in human pulmonary A549 cells by transcriptional and post transcriptional mechanisms. So, we suggested that the inhibitory effect of Dexamethazone may be due to its effect on COX2 and PGE2 that play an important role in hyphae formation and host cell damage (Mishra et al, 2014).…”

In Vitro Antibiofilm Activity of Eucarobustol E against Candida albicans

“…Confocal laser scanning microscopy (CLSM) was performed as previously described (32, 72) by using six-well plates containing plastic disks. Biofilms were incubated following the method described above and were costained with 10 g/ml of fluorescein diacetate (FDA) and 5 g/ml of propidium iodide (PI) for 30 min (72,73). Images were taken with a confocal laser scanning microscope (LSM700; Carl Zeiss).…”