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Ultrahigh-throughput functional profiling of microbiota communities.

Stanislav S Terekhov1, Ivan V Smirnov1,2, Maja V Malakhova3

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Summary

Researchers discovered a new antibiotic, amicoumacin A, from Siberian bear oral microbes using ultrahigh-throughput microfluidics. This method also revealed how bacteria resist antibiotics and their effects on different microbiomes.

Keywords:
antibiotic resistancedeep functional profilingmicrobiomemicrofluidicssingle-cell cultivation

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Area of Science:

  • Microbiology
  • Evolutionary Biology
  • Biochemistry

Background:

  • Microbiome analysis provides insights into host evolution, health, and behavior.
  • Exotic microbial sources are promising for discovering novel secondary metabolites.
  • Understanding bacterial interactions within microbiomes is complex but crucial for functional analysis.

Purpose of the Study:

  • To develop and apply an ultrahigh-throughput (uHT) microfluidic droplet platform for activity profiling of oral microbiomes.
  • To isolate bacterial strains with antimicrobial activity from the Siberian bear oral microbiota.
  • To identify the antibiotic responsible and elucidate its mechanism of action and self-resistance.

Main Methods:

  • Utilized an uHT microfluidic droplet platform for activity profiling of the Siberian bear oral microbiome.
  • Isolated *Bacillus* strains exhibiting antimicrobial activity against *Staphylococcus aureus*.
  • Employed genome mining, proteomics, metabolomics, and uHT quantitative single-cell analysis.

Main Results:

  • Identified amicoumacin A (Ami) as the antibiotic produced by *Bacillus* inhibiting *S. aureus* growth.
  • Elucidated a novel *Bacillus* self-resistance mechanism involving kinase AmiN and phosphatase AmiO.
  • Quantified Ami's efficacy against human and Siberian bear oral microbiomes using uHT single-cell analysis.

Conclusions:

  • The uHT microfluidic droplet platform is a powerful tool for antibiotic discovery.
  • This technology enables the quantification of external influences on microbiome activity.
  • The study highlights the potential of exploring exotic microbiomes for novel therapeutics.