Fluconazole resistance in Candida albicans is induced by Pseudomonas aeruginosa quorum sensing

• Published in: Scientific reports Vol. 10; no. 1; p. 7769
• Main Authors: Bandara, H. M. H. N., Wood, D. L. A., Vanwonterghem, I., Hugenholtz, P., Cheung, B. P. K., Samaranayake, L. P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.05.2020; Nature Publishing Group
• Subjects: 631/326; 631/326/193; 631/326/22/1292; 631/326/22/1434; Antifungal agents; Antifungal Agents - pharmacology; Antimicrobial agents; Antimicrobial resistance; Azoles; Biosynthesis; Biosynthetic Pathways; Candida albicans; Candida albicans - drug effects; Candida albicans - physiology; Cell membranes; Cellular stress response; Drug resistance; Drug Resistance, Fungal; Ergosterol; Ergosterol - biosynthesis; Fluconazole; Fluconazole - pharmacology; Gene Expression Regulation, Fungal - drug effects; Homoserine lactones; Humanities and Social Sciences; Microbial activity; Microbial Interactions; Microorganisms; multidisciplinary; Oxidative stress; Proteomics; Pseudomonas aeruginosa; Pseudomonas aeruginosa - physiology; Quorum Sensing; Science; Science (multidisciplinary); Yeasts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-64761-3

Microorganisms employ quorum sensing (QS) mechanisms to communicate with each other within microbial ecosystems. Emerging evidence suggests that intraspecies and interspecies QS plays an important role in antimicrobial resistance in microbial communities. However, the relationship between interkingdom QS and antimicrobial resistance is largely unknown. Here, we demonstrate that interkingdom QS interactions between a bacterium, Pseudomonas aeruginosa and a yeast, Candida albicans , induce the resistance of the latter to a widely used antifungal fluconazole. Phenotypic, transcriptomic, and proteomic analyses reveal that P. aeruginosa’s main QS molecule, N-(3-Oxododecanoyl)-L-homoserine lactone, induces candidal resistance to fluconazole by reversing the antifungal’s effect on the ergosterol biosynthesis pathway. Accessory resistance mechanisms including upregulation of C. albicans drug-efflux, regulation of oxidative stress response, and maintenance of cell membrane integrity, further confirm this phenomenon. These findings demonstrate that P. aeruginosa QS molecules may confer protection to neighboring yeasts against azoles, in turn strengthening their co-existence in hostile polymicrobial infection sites.