Deep Functional Profiling of Wild Animal Microbiomes Reveals Probiotic <i>Bacillus pumilus</i> Strains with a Common Biosynthetic Fingerprint

oleh: Margarita N. Baranova, Arsen M. Kudzhaev, Yuliana A. Mokrushina, Vladislav V. Babenko, Maria A. Kornienko, Maja V. Malakhova, Victor G. Yudin, Maria P. Rubtsova, Arthur Zalevsky, Olga A. Belozerova, Sergey Kovalchuk, Yuriy N. Zhuravlev, Elena N. Ilina, Alexander G. Gabibov, Ivan V. Smirnov, Stanislav S. Terekhov

Format: Article
Diterbitkan: MDPI AG 2022-01-01

Deskripsi

The biodiversity of microorganisms is maintained by intricate nets of interactions between competing species. Impaired functionality of human microbiomes correlates with their reduced biodiversity originating from aseptic environmental conditions and antibiotic use. Microbiomes of wild animals are free of these selective pressures. Microbiota provides a protecting shield from invasion by pathogens in the wild, outcompeting their growth in specific ecological niches. We applied ultrahigh-throughput microfluidic technologies for functional profiling of microbiomes of wild animals, including the skin beetle, Siberian lynx, common raccoon dog, and East Siberian brown bear. Single-cell screening of the most efficient killers of the common human pathogen <i>Staphylococcus aureus</i> resulted in repeated isolation of <i>Bacillus pumilus</i> strains. While isolated strains had different phenotypes, all of them displayed a similar set of biosynthetic gene clusters (BGCs) encoding antibiotic amicoumacin, siderophore bacillibactin, and putative analogs of antimicrobials including bacilysin, surfactin, desferrioxamine, and class IId cyclical bacteriocin. Amicoumacin A (Ami) was identified as a major antibacterial metabolite of these strains mediating their antagonistic activity. Genome mining indicates that Ami BGCs with this architecture subdivide into three distinct families, characteristic of the <i>B. pumilus</i>, <i>B. subtilis</i>, and <i>Paenibacillus</i> species. While Ami itself displays mediocre activity against the majority of Gram-negative bacteria, isolated <i>B. pumilus</i> strains efficiently inhibit the growth of both Gram-positive <i>S. aureus</i> and Gram-negative <i>E. coli</i> in coculture. We believe that the expanded antagonistic activity spectrum of Ami-producing <i>B. pumilus</i> can be attributed to the metabolomic profile predetermined by their biosynthetic fingerprint. Ultrahigh-throughput isolation of natural probiotic strains from wild animal microbiomes, as well as their metabolic reprogramming, opens up a new avenue for pathogen control and microbiome remodeling in the food industry, agriculture, and healthcare.