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Antibiotics (Basel). 2019 Nov 27;8(4). pii: E236. doi: 10.3390/antibiotics8040236.

Exploitation of Potentially New Antibiotics from Mangrove Actinobacteria in Maowei Sea by Combination of Multiple Discovery Strategies.

Author information

1
Department of Microbial Chemistry, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
2
Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
3
College of Basic Medical Sciences, Guilin Medical University, Guilin 541004, China.
4
Zhanjiang for R&D Marine Microbial Resources in the Beibu Gulf Rim, Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China.
5
College of Life Sciences, Jiamusi University, Jiamusi 154007, China.
6
College of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.
7
Department of Chemistry, Lomonosov Moscow State University, Moscow 119992, Russia.
8
Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow 143025, Russia.
9
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 119992, Russia.

Abstract

Rediscovery of known antibiotics from actinobacteria, especially Streptomyces, has become a bottleneck issue. Nowadays, more specific identification and dereplication could be acquired by a combination of modern analytic techniques with various databases. In this study, 261 actinobacterial strains were isolated from 8 mangrove soil samples by culture-dependent method. A total of 83 strains were selected to evaluate antibacterial activities and mechanisms by disc diffusion method and a unique double fluorescent protein reporter system (pDualrep2), respectively. Thirty-two strains exhibited antagonistic activity against at least one of the "ESKAPE" pathogens. Four Streptomyces strains (B475, B486, B353, and B98) showed strong inhibitory activity against Gram-positive bacteria and induced DNA damage SOS response. One Micromonospora strain (B704) exhibited inhibitory activity against several pathogens and induced attenuation-based translational inhibitors reporter. Seven members of quinoxaline-type antibiotics including quinomycin A, quinomycin monosulfoxide, and other five putative new analogues were found from the culture broth of strain B475 by a combination of anti-MRSA guide, HPTLC, HPLC-UV, and UPLC-UV-HRESIMS/MS analysis, Chemspider searching, and MS/MS-based molecular networking analysis. In conclusion, this study not only demonstrated that mangrove is a rich source of actinobacteria with the potentially new antibiotics but showed rapid dereplication of known antibiotics in the early stage can improve efficiency for the discovery of new antibiotics.

KEYWORDS:

ESKAPE; GNPS; Maowei Sea; actinobacteria; dereplication; diversity; mangrove; quinomycins

PMID:
31783564
DOI:
10.3390/antibiotics8040236
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