Prospects for New Antibiotics Discovered Through Genome Analysis

R. Malviya, Ashutosh Kumar Singh, Rishav Sharma
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Abstract

Antibiotic-resistant illnesses are on the rise worldwide, and the pipeline for developing new antibiotics is drying up. As a result, researchers need to create novel compounds with antimicrobial action. Recent decades have seen a dearth of novel antibiotics because of the reliance on conventional empirical screening procedures using both natural and synthetic chemicals to find them. There is hope that the massive amount of bacterial genome sequence data that has become accessible since the sequencing of the first bacterial genome more than 20 years ago might help lead to the development of new antibiotic drugs. Genes with significant levels of conservation both within and between bacterial species can be found using comparative genomic techniques; these genes may be involved in essential bacterial functions. Bioactive chemicals found in natural products have been successfully used in treating everything from infectious diseases to cancer, but over the past 20-30 years, the effectiveness of screening methods based on fermentation has decreased. Researchers urgently need answers to the unmet demand for bacterial infection resistance. Now more than ever, with the advent of cheap, high-throughput genomic sequencing technology, natural product discovery can be revitalized. Using bioinformatics, investigators may foretell whether or not a certain microbial strain would generate compounds with novel chemical structures, which may have novel modes of action in inhibiting bacterial growth. This manuscript describes how this potential might be utilised, with a particular emphasis on manipulating the expression of dormant biosynthetic gene clusters that are hypothesised to encode new antibiotics. Additionally, it consolidates the work of the past and the present to utilise bacterial genomic data in the identification and development of new antibiotics.
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通过基因组分析发现新抗生素的前景
抗生素耐药性疾病在世界范围内呈上升趋势,开发新抗生素的渠道正在枯竭。因此,研究人员需要创造出具有抗菌作用的新型化合物。近几十年来,由于依赖传统的经验性筛选程序,使用天然和合成化学物质来寻找新型抗生素,因此缺乏新型抗生素。自20多年前第一个细菌基因组测序以来,大量的细菌基因组序列数据已经变得触手可及,人们希望这些数据可能有助于开发新的抗生素药物。使用比较基因组技术可以发现细菌物种内部和物种之间具有显著保护水平的基因;这些基因可能与细菌的基本功能有关。在天然产物中发现的生物活性化学物质已经成功地用于治疗从传染病到癌症的各种疾病,但在过去的20-30年里,基于发酵的筛选方法的有效性有所下降。研究人员迫切需要解决细菌感染耐药性的未满足需求。现在比以往任何时候,随着廉价,高通量基因组测序技术的出现,自然产物的发现可以振兴。利用生物信息学,研究人员可以预测某种微生物菌株是否会产生具有新化学结构的化合物,这些化合物可能具有抑制细菌生长的新作用模式。这篇手稿描述了如何利用这种潜力,特别强调操纵休眠生物合成基因簇的表达,这些基因簇被假设为编码新的抗生素。此外,它巩固了过去和现在的工作,利用细菌基因组数据识别和开发新的抗生素。
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来源期刊
Anti-Infective Agents
Anti-Infective Agents Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
1.50
自引率
0.00%
发文量
47
期刊介绍: Anti-Infective Agents publishes original research articles, full-length/mini reviews, drug clinical trial studies and guest edited issues on all the latest and outstanding developments on the medicinal chemistry, biology, pharmacology and use of anti-infective and anti-parasitic agents. The scope of the journal covers all pre-clinical and clinical research on antimicrobials, antibacterials, antiviral, antifungal, and antiparasitic agents. Anti-Infective Agents is an essential journal for all infectious disease researchers in industry, academia and the health services.
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