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 adh1Δ/Δ, 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 adh1Δ/Δ 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 adh1Δ/Δ 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.

铜绿假单胞菌和白色念珠菌是机会病原体，它们的相互作用涉及分泌产物乙醇和吩嗪。在这里，我们通过双序列分析描述了乙醇在混合物种共培养中的作用。P。铜绿假单胞菌和Ç。在单培养或与产乙醇的C共同培养后，评估了白色的转录组。白色假丝酵母或Ç。缺少一级乙醇脱氢酶Adh1的白色念珠菌突变体。使用KEGG途径充实和eADAGE方法的转录组测序数据的分析表明，在一些P。铜绿对C的回应。白色念珠菌产生的乙醇，包括由PhoB调节的非典型低磷酸盐反应的诱导。Ç。白色念珠菌野生型，而不是Ç。白色假丝酵母ADH1 Δ/Δ，诱导P。铜绿产生的5-甲基-吩嗪-1-羧酸（5-MPCA），在真菌细胞内形成红色衍生物，并表现出抗真菌活性。在这里，我们表明，Ç。白色假丝酵母ADH1 Δ/Δ不再激活P。铜绿PhoB和PhoB调节的磷酸酶活性，即外源乙醇弥补了这一缺陷，并且乙醇足以激活单一物种P中的PhoB 。铜绿菌培养物的磷酸盐水平允许。共培养中乙醇和磷酸盐的交集在C中反显。白色的; Ç。白色念珠菌adh1Δ /Δ增加了受Pho4调节的基因C的表达。白色念珠菌转录因子响应低磷酸盐和PHO4依赖磷酸酶活性。总之，这些结果表明，Ç。白色念珠菌产生的乙醇刺激磷。铜绿假单胞菌PhoB活性和5-MPCA介导的拮抗作用，并且两种反应均取决于局部磷酸盐浓度。此外，我们的数据表明，一种物种清除磷酸盐可改善另一种物种的磷酸盐获取，从而突显了微生物群落中复杂的动力学。