Strategies for Discovering New Antibiotics from Bacteria in the Post-Genomic Era
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REVIEW ARTICLE
Strategies for Discovering New Antibiotics from Bacteria in the Post‑Genomic Era Jia‑Wei Zhu1 · Si‑Jia Zhang1 · Wen‑Guang Wang1 · Hui Jiang1 Received: 12 March 2020 / Accepted: 3 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract New antibiotics are urgently required in clinical treatment and agriculture with the development of antimicrobial resistance. However, products discovered by repeating previous strategies are either not antibiotics or already known antibiotics. There is a growing demand for efficient strategies to discover new antibiotics. With the continuous improvement of gene sequencing technology and genomic data, some mining strategies have emerged. These strategies are expected to alleviate the current dilemma of antibiotics. In this review, we discuss the recent advances in discovery of bacterial antibiotics from the following aspects: activation of silent gene clusters, genome mining and metagenome mining. In the future, we envision the discovery of natural antibiotic will be accelerated by the combination of these strategies. Keywords Antibiotics · Biosynthetic gene cluster · Gene mining · Genome mining
Introduction Natural antibiotics are a class of secondary metabolites produced by organisms, which have diverse biological activities, such as anti-pathogenic, interference in the development of living cells. According to their chemical structures and the mode of action, antibiotics can be classified into β-lactams, aminoglycosides, macrolides, tetracyclines and so on [1]. Since the discovery of the first natural antibiotic penicillin in 1929, a number of antibiotics with wide application and great value in agriculture and clinic have been identified [2]. However, abuse of antibiotics has promoted the rapid rise of antimicrobial resistance, which has become one of the biggest threats to prevention and treatment of an increasing number of infections [3]. According to the World Health Organization (WHO), antimicrobial agents currently developed cannot sufficiently address the problem of Gram-negative bacteria with broad resistance or pan-drug resistance (e.g., carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa) [4]. Statistics show that in Europe and the USA alone, as many as 50,000 lives are lost each year due to antibiotic-resistant infections [5]. * Hui Jiang [email protected] 1
College of Life Sciences, Zhejiang University, 866 Yuhangtang Road, Hang Zhou, China
Therefore, new antibiotics exhibiting lack of pre-existing cross-resistance are urgently needed. The discovery of antibiotics in the twentieth century was one of the greatest achievements in medicine, and most antibiotics are still used clinically. Selman Waksman was the first to perform a systematic study of soil bacteria as producers of antimicrobial compounds and found that bacteria could produce their own antibiotics for competitive growth. Through the systematic agar overlay process, more than 10,000 different microbial strains were screened.
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