Ultrahigh-throughput functional profiling of microbiota communities

被引：83

作者：

Terekhov, Stanislav S. ^{[1
]}

Smirnov, Ivan V. ^{[1
,2
]}

Malakhova, Maja V. ^{[3
]}

Samoilov, Andrei E. ^{[3
]}

Manolov, Alexander I. ^{[3
]}

Nazarov, Anton S. ^{[1
]}

Danilov, Dmitry V. ^{[1
]}

Dubiley, Svetlana A. ^{[4
,5
]}

Osterman, Ilya A. ^{[5
,6
]}

Rubtsova, Maria P. ^{[5
,6
]}

Kostryukova, Elena S. ^{[3
]}

Ziganshin, Rustam H. ^{[1
]}

Kornienko, Maria A. ^{[3
]}

Vanyushkina, Anna A. ^{[3
]}

Bukato, Olga N. ^{[3
]}

Ilina, Elena N. ^{[3
]}

Vlasov, Valentin V. ^{[7
]}

Severinov, Konstantin V. ^{[5
,8
]}

Gabibov, Alexander G. ^{[1
]}

Altman, Sidney ^{[9
,10
]}

机构：

[1] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia

[2] Natl Res Univ, Higher Sch Econ, Moscow 101000, Russia

[3] Fed Med & Biol Agcy, Fed Res & Clin Ctr Phys Chem Med, Moscow 119435, Russia

[4] Russian Acad Sci, Inst Gene Biol, Moscow 119334, Russia

[5] Skolkovo Inst Sci & Technol, Skolkovo 143026, Russia

[6] Lomonosov Moscow State Univ, Dept Chem, Moscow 119991, Russia

[7] Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia

[8] Rutgers State Univ, Waksman Inst Microbiol, Piscataway, NJ 08901 USA

[9] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA

[10] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2018年 / 115卷 / 38期

关键词：

microbiome; microfluidics; deep functional profiling; antibiotic resistance; single-cell cultivation; BIOSYNTHESIS GENE-CLUSTER; GUT MICROBIOTA; AMICOUMACINS; DNA;

D O I：

10.1073/pnas.1811250115

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 self-resistance 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.

引用

页码：9551 / 9556

页数：6

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