Dataset Information

Microbial competition between Escherichia coli and Candida albicans reveals a soluble fungicidal factor.

ABSTRACT: Localized and systemic fungal infections caused by Candida albicans can lead to significant mortality and morbidity. However, severe C. albicans infections are relatively rare, occurring mostly in the very young, the very old, and immunocompromised individuals. The fact that these infections are rare is interesting because as much as 80 percent of the population is asymptomatically colonized with C. albicans. It is thought that members of the human microbiota and the immune system work in concert to reduce C. albicans overgrowth through competition and modification of the growth environment. Here, we report that Escherichia coli (strain MG1655) outcompetes and kills C. albicans (strain SC5314) in vitro. We find that E. coli produces a soluble factor that kills C. albicans in a magnesium-dependent fashion such that depletion of available magnesium is essential for toxicity.

SUBMITTER: Cabral DJ

PROVIDER: S-EPMC5961918 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Microbial competition between Escherichia coli and Candida albicans reveals a soluble fungicidal factor.

Cabral Damien J DJ Penumutchu Swathi S Norris Colby C Morones-Ramirez Jose Ruben JR Belenky Peter P

Microbial cell (Graz, Austria) 20180307 5

Localized and systemic fungal infections caused by Candida albicans can lead to significant mortality and morbidity. However, severe C. albicans infections are relatively rare, occurring mostly in the very young, the very old, and immunocompromised individuals. The fact that these infections are rare is interesting because as much as 80 percent of the population is asymptomatically colonized with C. albicans. It is thought that members of the human microbiota and the immune ...[more]

PMID: 29796389

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Project description:Among the several mechanisms of multidrug resistance (MDR), overexpression of drug efflux pumps CaCdr1p and CaMdr1p belonging to ATP binding cassette (ABC) and major facilitator superfamily (MFS) respectively remain the predominant mechanisms of candidal infections. Therefore inhibiting or modulating the function of these transporters continues to draw attention as effective strategy to combat MDR. We have previously reported the antifungal potential of Geraniol (Ger), a natural monoterpenoid from Palmarosa oil, against Candida albicans. Herein, we explored the fungicidal nature of Ger. The Rhodamine 6G (R6G) and Nile red accumulation confirms the specific effect on CaCdr1p. Mechanistic insights with Candida cells overexpressing CaCdr1p and CaMdr1p revealed that Ger specifically modulates CaCdr1p activity. Kinetic studies further unraveled the competitive inhibition of Ger for R6G efflux as evident from increased apparent Km without affecting Vmax value. The effect of Ger on CaCdr1p was substantiated by molecular docking analyses, which depicted in-silico binding affinity of Ger with CaCdr1p and explored that Ger binds to the active site of CaCdr1p with higher binding energy. Although RT-PCR and western blot revealed no change in expressions of CDR1 and CaCdr1p, confocal microscopy images however depicted CaCdr1p mislocalization in presence of Ger. Interestingly, Ger was synergistic (FICI<0.5) with fluconazole (FLC) which is a well known antifungal drug. Furthermore, Ger sensitizes the FLC sensitive and resistant clinical matched pair of isolates Gu4/Gu5 and led to abrogated R6G efflux and depleted ergosterol. Furthermore, Rhodamine B labeling demonstrates altered mitochondrial potential with Ger which suggest possible linkage of dysfunctional mitochondria with CaCdr1p activity. We also estimated phenotypic virulence marker extracellular phospholipase activity which was considerably diminished along with inhibited cell adherence and biofilm biomass. Lastly, antifungal efficacy of Ger was demonstrated by enhanced survival of Caenorhabditis elegans model and negligible hemolytic activity (20%). Together, modulation of efflux pump activity by Ger and FLC synergism represent a promising approach for combinatorial treatment of candidiasis.

Dataset Information

Microbial competition between Escherichia coli and Candida albicans reveals a soluble fungicidal factor.

Publications

Microbial competition between <i>Escherichia coli</i> and <i>Candida albicans</i> reveals a soluble fungicidal factor.

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