Varied mutual growth inhibition between commensal yeasts andE. colistrains

Interkingdom interactions between bacteria and fungi are an emerging research field that provides insights into pathological, environmental, and microbiota-related relationships. However, the mechanisms governing these interactions, particularly in the context of microbial resistance, remain largely unknown. This study aims to enhance our understanding of the complex interactions between differentCandida, Nakaseomyces and Sacharomycesspecies from the human microbiota and two not isogenic strains ofEscherichia coli(antibiotic-susceptibleE. coli-ATCC and multidrug-resistantE. coli-OXA48). Forty-nineCandidastrains were co-cultured with the twoE. colistrains. Both bacterial and yeast growth was monitored using flow cytometry and compared to monocultures. The effect ofyeastculture supernatants onE. coliproliferation was also investigated. Metabolomic fingerprints and metabolite identification were performed using mass spectrometry-based approaches followed by multiblock statistical analyses. The inhibitory powers (IP) of yeasts againstE. coliand vice versa varied significantly among fungal species.N. glabrataexhibited the strongest inhibition againstE. coli-ATCC, whileCandida lusitaniae, C. kefyr, C. krusei, C. tropicalis, andC. dubliniensisshowed lower IPs.C. parapsilosisandSaccharomyces cerevisiaehad no inhibitory effects. AgainstE. coli-OXA48, most yeasts displayed no inhibition, except forN. glabrata. Conversely,E. coliinhibited yeast growth more effectively, particularlyCandida albicans. Fungal supernatants fromS. cerevisiae, C. lusitaniae, andN. glabratashowed the highest inhibitory effects onE. coli-ATCC, whileS. cerevisiae, C. krusei, andC. lusitaniaewere most effective againstE. coli-OXA48. Unsupervised metabolite profiling data analysis with multiblock approach highlighted a clustering of samples according to yeast species. Regarding inhibitory power onE. coli(ATCC or OXA48), active supernatants tend to cluster together suggesting the presence of similar metabolites; some were further characterized. This study highlights the diverse interactions betweenE. coliand commensal yeasts. From an applied perspective, these findings pave the way for identifying probiotics or postbiotics with potential applications in combating multidrug-resistant bacteria through novel antimicrobial compounds.