Abstract
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.
Highlights
Microorganisms employ quorum sensing (QS) mechanisms to communicate with each other within microbial ecosystems
No MIC80 of fluconazole was observed when C. albicans was exposed to the antifungal agent alongside C12AHL within the concentration ranges assessed in this study
C12AHL demonstrated a 20% maximum inhibition of C. albicans growth when treated with 100 μg mL−1
Summary
Microorganisms employ quorum sensing (QS) mechanisms to communicate with each other within microbial ecosystems. 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. QS is essential for microbes to optimize their survival in dynamic, constantly challenging niches, as the chemical messengers help correlate individual cellular functions to microbial community-based requirements[14] These include regulation of biofilm development and maturation, motility www.nature.com/scientificreports and virulence, bacterial sporulation, formation of fungal fruiting bodies, conjugal plasmid transfer and antimicrobial resistance, and antibiotic synthesis[15,16,17]. We demonstrate that P. aeruginosa C12AHL induces C. albicans’ fluconazole resistance through multiple mechanisms, predominantly by facilitating fungal ergosterol synthesis and restoring its cell wall integrity
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