Ultrahigh-throughput functional profiling of microbiota communities

Stanislav S. Terekhov, Ivan V. Smirnov, Maja V. Malakhova, Andrei E. Samoilov, Alexander I. Manolo, Anton S. Nazarov, Dmitry V. Danilov, Svetlana A. Dubiley, Ilya A. Osterman, Maria P. Rubtsova, Elena S. Kostryukova, Rustam H. Ziganshin, Maria A. Kornienko, Anna A. Vanyushkina, Olga N. Bukato, Elena N. Ilina, Valentin V. Vlasov, Konstantin V. Severinov, Alexander G. Gabibov, Sidney Altmani

    Research output: Contribution to journalArticlepeer-review

    53 Citations (Scopus)

    Abstract

    Microbiome spectra serve as critical clues to elucidate the evolutionary biology pathways, potential pathologies, and even behavioral patterns of the host organisms. Furthermore, exotic sources of microbiota represent an unexplored niche to discover microbial secondary metabolites. However, establishing the bacterial functionality is complicated by an intricate web of interactions inside the microbiome. Here we apply an ultrahigh-throughput (uHT) microfluidic droplet platform for activity profiling of the entire oral microbial community of the Siberian bear to isolate Bacillus strains demonstrating antimicrobial activity against Staphylococcus aureus. Genome mining allowed us to identify antibiotic amicoumacin A (Ami) as responsible for inhibiting the growth of S. Aureus. Proteomics and metabolomics revealed a unique mechanism of Bacillus selfresistance to Ami, based on a subtle equilibrium of its deactivation and activation by kinase AmiN and phosphatase AmiO, respectively. We developed uHT quantitative single-cell analysis to estimate antibiotic efficacy toward different microbiomes and used it to determine the activity spectra of Ami toward human and Siberian bear microbiota. Thus, uHT microfluidic droplet platform activity profiling is a powerful tool for discovering antibiotics and quantifying external influences on a microbiome.

    Original languageEnglish
    Pages (from-to)9551-9556
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume115
    Issue number38
    DOIs
    Publication statusPublished - 18 Sep 2018

    Keywords

    • Antibiotic resistance
    • Deep functional profiling
    • Microbiome
    • Microfluidics
    • Single-cell cultivation

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