Varied mutual growth inhibition between commensal yeasts and strains

Pingault--Ordronneau, E.; Francois, A.; Ragoobeer, V.; Chambon, T.; Cockx, B.; Elias, A. J.; Szabo, D.; Gugolya, M.; Kreft, J.-U.; Cloteau, C.; Levercan, D.; Croyal, M.; Delhaye, T.; Rondeau, D.; Roullier, C.; Bertrand, S.; Picot, C.; Le Pape, P.; Batard, E.; Alvarez-Rueda, N.

doi:10.1101/2025.05.29.656793

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bioRxiv · 10.1101/2025.05.29.656793

Varied mutual growth inhibition between commensal yeasts and strains

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Abstract

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 different Candida, Nakaseomyces and Sacharomyces species from the human microbiota and two not isogenic strains of Escherichia coli (antibiotic-susceptible E. coli-ATCC and multidrug-resistant E. coli-OXA48). Forty-nine Candida strains were co-cultured with the two E. coli strains. Both bacterial and yeast growth was monitored using flow cytometry and compared to monocultures. The effect of yeast culture supernatants on E. coli proliferation 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 against E. coli and vice versa varied significantly among fungal species. N. glabrata exhibited the strongest inhibition against E. coli-ATCC, while Candida lusitaniae, C. kefyr, C. krusei, C. tropicalis, and C. dubliniensis showed lower IPs. C. parapsilosis and Saccharomyces cerevisiae had no inhibitory effects. Against E. coli-OXA48, most yeasts displayed no inhibition, except for N. glabrata. Conversely, E. coli inhibited yeast growth more effectively, particularly Candida albicans. Fungal supernatants from S. cerevisiae, C. lusitaniae, and N. glabrata showed the highest inhibitory effects on E. coli-ATCC, while S. cerevisiae, C. krusei, and C. lusitaniae were most effective against E. coli-OXA48. Unsupervised metabolite profiling data analysis with multiblock approach highlighted a clustering of samples according to yeast species. Regarding inhibitory power on E. 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 between E. coli and 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.

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Pingault--Ordronneau, E., Francois, A., Ragoobeer, V., Chambon, T., Cockx, B., Elias, A. J., Szabo, D., Gugolya, M., Kreft, J.-U., Cloteau, C., Levercan, D., Croyal, M., Delhaye, T., Rondeau, D., Roullier, C., Bertrand, S., Picot, C., Le Pape, P., Batard, E., Alvarez-Rueda, N.. 2025-05-29. Varied mutual growth inhibition between commensal yeasts and strains. https://doi.org/10.1101/2025.05.29.656793

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