抗生素耐药性危机与新型抗生素的开发。

IF 5.7 2区 生物学
Harald Brüssow
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引用次数: 0

摘要

据《2019 年全球疾病负担报告》估计,与感染相关的死亡人数达 1400 万,成为仅次于缺血性心脏病的第二大死因。细菌病原体导致的死亡人数为 770 万,细菌抗生素耐药性导致的死亡人数为 130 万,这说明对新型抗生素的需求十分明显。1930-1960 年是抗生素研发的黄金时期。本世纪初,由于新型抗生素化学库筛选失败,推出新抗生素的成本高昂(估计每种注册药物的成本为 14 亿美元),以及新型抗生素难以获得投资回报,制药业大多退出了这一领域。本期小人国报告分析了阻碍新抗生素注册的是科学障碍还是经济障碍。从科学角度讲,近年来在以下方面取得了重大进展:确定克服革兰氏阴性病原体渗透屏障所需的化学特性;通过全模块化合成合适的分子来扩展候选抗生素的化学空间;将生物勘探扩展到以前 "无法培养 "的细菌或不常见的细菌;攻击细菌外膜上的细菌靶标;以及从结构生物学、基因组学、分子遗传学、系统发育分析和深度机器学习方法中寻找支持。然而,这些研究活动大多是由财力有限的学术研究人员和生物技术公司开展的。由此看来,新抗生素的开发(经常被描述为 "管道干涸")与其说是受到缺乏科学洞察力的限制,不如说是受到缺乏将这些发现推向市场所需的货币资源的限制,尽管公共部门最近在财政推动和拉动方面做出了努力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The antibiotic resistance crisis and the development of new antibiotics

The antibiotic resistance crisis and the development of new antibiotics

The Global Burden of Disease report of 2019 estimated 14 million infection-related deaths, making it the second leading cause of death after ischaemic heart disease. Bacterial pathogens accounted for 7.7 million deaths and deaths attributable to bacterial antibiotic resistance amounted to 1.3 million, describing a clear demand for novel antibiotics. Antibiotic development had its golden age in 1930–1960. Following failures in the screening of chemical libraries for novel antibiotics at the beginning of this century, the high cost of launching new antibiotics (estimated at US$ 1.4 billion per registered drug) and difficulties in achieving a return of investment for novel antibiotics, pharmaceutical industry has mostly left the field. The current Lilliput review analyses the question whether scientific or economic hurdles prevented the registration of new antibiotics. Scientifically, substantial progress has been achieved over recent years to define the chemical properties needed to overcome the permeation barrier in Gram-negative pathogens; in extending the chemical space of antibiotic candidates by full modular synthesis of suitable molecules; by extending bioprospecting to previously ‘unculturable’ bacteria or unusual bacteria; by attacking bacterial targets on the outer bacterial membrane; and by looking for support from structural biology, genomics, molecular genetics, phylogenetic analyses and deep machine learning approaches. However, these research activities were mostly conducted by academic researchers and biotech companies with limited financial resources. It thus seems that the development of new antibiotics, frequently described as the drying of the pipeline, is less limited by lack of scientific insight than by lack of the mobilization of the monetary resources needed to bring these discoveries to the market despite recent financial push and pull efforts of the public sector.

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来源期刊
Microbial Biotechnology
Microbial Biotechnology Immunology and Microbiology-Applied Microbiology and Biotechnology
CiteScore
11.20
自引率
3.50%
发文量
162
审稿时长
1 months
期刊介绍: Microbial Biotechnology publishes papers of original research reporting significant advances in any aspect of microbial applications, including, but not limited to biotechnologies related to: Green chemistry; Primary metabolites; Food, beverages and supplements; Secondary metabolites and natural products; Pharmaceuticals; Diagnostics; Agriculture; Bioenergy; Biomining, including oil recovery and processing; Bioremediation; Biopolymers, biomaterials; Bionanotechnology; Biosurfactants and bioemulsifiers; Compatible solutes and bioprotectants; Biosensors, monitoring systems, quantitative microbial risk assessment; Technology development; Protein engineering; Functional genomics; Metabolic engineering; Metabolic design; Systems analysis, modelling; Process engineering; Biologically-based analytical methods; Microbially-based strategies in public health; Microbially-based strategies to influence global processes
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