Prostaglandins Leukot Essent Fatty Acids. 2017 Feb;117:36-46. doi: 10.1016/j.plefa.2017.01.008.

Pseudomonas aeruginosa produces aspirin insensitive eicosanoids and contributes to the eicosanoid profile of polymicrobial biofilms with Candida albicans.




During infection, arachidonic acid, a polyunsaturated fatty acid is released from host cells (reviewed in Fourie et al., 2016). This fatty acid is used by host cells to produce eicosanoids, a class of lipids that have the ability to influence the immune response. For example, prostaglandin E2 can inhibit the Th1 response and promote the Th2 response, affecting the efficiency of the host to clear infection.

When Candida albicans, an opportunistic fungal pathogen is exposed to this immunomodulatory precursor or its oxidised products, it affects the ability of the fungus to switch between morphologies, such as yeast (associated with dissemination in the host) and hyphal morphologies (associated with invasive growth and tissue damage) (Alem & Douglas, 2004). However, the mechanism of this is still unknown. A frequent co-isolate of C. albicans infection, especially in cystic fibrosis patients, is the bacterium Pseudomonas aeruginosa (Fourie et al., 2016). Provided by the close-proximity of co-localized infection, these two pathogens show considerable interaction of an unfriendly nature. Furthermore, both of these microorganisms form biofilms (structures of cells attached to a surface, encased in an extracellular matrix) that protect them against attack by antimicrobials and immune cells. Figure 1 indicates an interaction between the bacterial and fungal cells. The antagonistic interaction between C. albicans and P. aeruginosa is mediated by physical factors, where P. aeruginosa kills C. albicans cells, as well as through secreted molecules. This interaction can be expanded to include the production of eicosanoids (Fourie et al., 2017). This is because both C. albicans and P. aeruginosa has been identified to produce eicosanoids. This may not only affect infection dynamics, but also the interaction between the yeast and the bacterium. Our group aims to contribute to knowledge of the interaction of C. albicans and P. aeruginosa, with special attention being paid to the influence of arachidonic acid in this interaction. This is being done by evaluating not only isolated factors, but to look at the whole transcriptomic response of both microorganisms towards the fatty acid, on their own, as well as in a polymicrobial biofilm. This is done by quantifying the amount of messenger RNA transcripts, which directly correlates to the expression of proteins in response to specific stimuli. Determining the effect of arachidonic acid on infective agents is of great importance, due to the ubiquitous nature of arachidonic acid in the body. Early results indicate that C. albicans may undergo structural changes in terms of membrane and cell wall composition (Figure 2) that may drastically affect its ability to not only infect the host, but also its resistance to antifungal agents.

In addition to this, we are hoping to expand knowledge regarding the influence of arachidonic acid on the virulence of both species during co-incubation, as well as how eicosanoids are produced by C. albicans and P. aeruginosa. This information may illuminate novel therapeutic strategies to treat mono- and polymicrobial infections by C. albicans and P. aeruginosa, as well as give insight into treatment of other microbial infections.



Figure 1. Scanning Electron Micrograph of Pseudomonas aeruginosa cells interacting with Candida albicans cell in a polymicrobial biofilm. Scale bar represents 1 μm.



Figure 2. Localization of Candida albicans genes that are enriched in response to arachidonic acid. Division of pie chart according to fold enrichment of Gene Ontology terms (PANTHER).




Alem, M. A. S. and Douglas, L. J. (2004). Effects of aspirin and other nonsteroidal anti-inflammatory drugs on biofilms and planktonic cells of Candida albicans. Antimicrob Agents Chemother 48, 41-47

Fourie, R., Ells, R., Swart, C. W. Sebolai, O. M., Albertyn, J. and Pohl, C. H. (2016). Candida albicans and Pseudomonas aeruginosa interaction, with focus on the role of eicosanoids. Front Physiol 7:64. doi: 10.3389/fphys.2016.00064

Fourie, R., Ells, R., Kemp, G., Sebolai, O. M., Albertyn, J. and Pohl, C. H. (2017). Pseudomonas aeruginosa produces aspirin insensitive eicosanoids and contributes to the eicosanoid profile of polymicrobial biofilms with Candida albicans. Prostaglandins Leukot Essent Fatty Acids 117, 36-46.