Dataset Information

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

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.

SUBMITTER: Bandara HMHN

PROVIDER: S-EPMC7211000 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Bandara H M H N HMHN Wood D L A DLA Vanwonterghem I I Hugenholtz P P Cheung B P K BPK Samaranayake L P LP

Scientific reports 20200508 1

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 resi ...[more]

PMID: 32385378

Similar Datasets

Project description:Quorum sensing (QS) is a cell-density-dependent, intercellular communication system mediated by small diffusible signaling molecules. QS regulates a range of bacterial behaviors, including biofilm formation, virulence, drug resistance mechanisms, and antibiotic tolerance. Enzymes capable of degrading signaling molecules can interfere in QS-a process termed as quorum quenching (QQ). Remarkably, previous work reported some cases where enzymatic interference in QS was synergistic to antibiotics against Pseudomonas aeruginosa. The premise of combination therapy is attractive to fight against multidrug-resistant bacteria, yet comprehensive studies are lacking. Here, we evaluate the effects of QS signal disruption on the antibiotic resistance profile of P. aeruginosa by testing 222 antibiotics and antibacterial compounds from 15 different classes. We found compelling evidence that QS signal disruption does indeed affect antibiotic resistance (40% of all tested compounds; 89/222), albeit not always synergistically (not synergistic for 19% of compounds; 43/222). For some tested antibiotics, such as sulfathiazole and trimethoprim, we were able to relate the changes in resistance caused by QS signal disruption to the modulation of the expression of key genes of the folate biosynthetic pathway. Moreover, using a P. aeruginosa-based Caenorhabditis elegans killing model, we confirmed that enzymatic QQ modulates the effects of antibiotics on P. aeruginosa's pathogenicity in vivo. Altogether, these results show that signal disruption has profound and complex effects on the antibiotic resistance profile of P. aeruginosa. This work suggests that combination therapy including QQ and antibiotics should be discussed not globally but, rather, in case-by-case studies. IMPORTANCE Quorum sensing (QS) is a cell-density-dependent communication system used by a wide range of bacteria to coordinate behaviors. Strategies pertaining to the interference in QS are appealing approaches to control microbial behaviors that depend on QS, including virulence and biofilms. Interference in QS was previously reported to be synergistic with antibiotics, yet no systematic assessment exists. Here, we evaluate the potential of combination treatments using the model opportunistic human pathogen Pseudomonas aeruginosa PA14. In this model, collected data demonstrate that QS largely modulates the antibiotic resistance profile of PA14 (for more than 40% of the tested drugs). However, the outcome of combination treatments is synergistic for only 19% of them. This research demonstrates the complex relationship between QS and antibiotic resistance and suggests that combination therapy including QS inhibitors and antibiotics should be discussed not globally but, rather, in case-by-case studies.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets