Conditional antagonism in co-cultures of Pseudomonas aeruginosa and Candida albicans: An intersection of ethanol and phosphate signaling distilled from dual-seq transcriptomics

• Published in: PLoS genetics Vol. 16; no. 8; p. e1008783
• Main Authors: Doing, Georgia, Koeppen, Katja, Occipinti, Patricia, Harty, Colleen E, Hogan, Deborah A
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 19.08.2020; Public Library of Science (PLoS)
• Subjects: Antagonism; Antifungal activity; Biofilms; Biology and Life Sciences; Candida albicans; Carboxylic acids; Cell culture; Cellular signal transduction; Enzymes; Ethanol; Gene expression; Genetic aspects; Kinases; Medicine; Medicine and Health Sciences; Opportunist infection; Pathogens; Phenazine; Phenazine-1-carboxylic acid; Phosphatase; Phosphate; Phosphates; Physical Sciences; Physiological aspects; Pseudomonas aeruginosa; Research and Analysis Methods; Ribonucleic acid; RNA; Species; Transcription factors; United States; United States > US; New Hampshire
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1008783

Pseudomonas aeruginosa and Candida albicans are opportunistic pathogens whose interactions involve the secreted products ethanol and phenazines. Here, we describe the role of ethanol in mixed-species co-cultures by dual-seq analyses. P. aeruginosa and C. albicans transcriptomes were assessed after growth in mono-culture or co-culture with either ethanol-producing C. albicans or a C. albicans mutant lacking the primary ethanol dehydrogenase, Adh1. Analysis of the RNA-Seq data using KEGG pathway enrichment and eADAGE methods revealed several P. aeruginosa responses to C. albicans-produced ethanol including the induction of a non-canonical low-phosphate response regulated by PhoB. C. albicans wild type, but not C. albicans adh1[DELTA]/[DELTA], induces P. aeruginosa production of 5-methyl-phenazine-1-carboxylic acid (5-MPCA), which forms a red derivative within fungal cells and exhibits antifungal activity. Here, we show that C. albicans adh1[DELTA]/[DELTA] no longer activates P. aeruginosa PhoB and PhoB-regulated phosphatase activity, that exogenous ethanol complements this defect, and that ethanol is sufficient to activate PhoB in single-species P. aeruginosa cultures at permissive phosphate levels. The intersection of ethanol and phosphate in co-culture is inversely reflected in C. albicans; C. albicans adh1[DELTA]/[DELTA] had increased expression of genes regulated by Pho4, the C. albicans transcription factor that responds to low phosphate, and Pho4-dependent phosphatase activity. Together, these results show that C. albicans-produced ethanol stimulates P. aeruginosa PhoB activity and 5-MPCA-mediated antagonism, and that both responses are dependent on local phosphate concentrations. Further, our data suggest that phosphate scavenging by one species improves phosphate access for the other, thus highlighting the complex dynamics at play in microbial communities.