SELECTAR - Selection for antimicrobial resistance by antimicrobial production waste

SELECTAR - 通过抗菌剂生产废物筛选抗菌剂耐药性

• 批准号: NE/T01301X/1
• 负责人: Alan McNally
• 金额: $ 127.01万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FT01301X%2F1
• 关键词: SELECTAR; Selection; antimicrobial; resistance; production

Antibiotics are one of the most crucial medicines on the planet. Without them we are unable to treat the vast majority of infectious diseases, ranging from life threatening intestinal infections and blood stream infections, to treating debilitating chronic infections such as urinary tract infections and respiratory infections. Antibiotics are required to prevent the deaths of patients suffering from respiratory diseases such as CF and COPD, and are the corner stone of treatments for diseases such as cancer and leukaemia where it is necessary to prevent infections during treatment. The majority of the worlds antibiotics are produced in pharmaceutical factories in India. Antibiotics can be produced by chemical synthesis or by growing vast number of the microorganisms which naturally produce them. Either method results in the production of large quantities of waste, potentially containing active antibiotics and/or chemicals which may be toxic to bacteria and other cell types. This waste goes through treatment plants before being released into the environment. This creates an enormous potential issue, as the more we expose bacteria to antibiotics the faster they evolve resistance to the drugs meaning they cant be used to treat infections. There is also the possibility that release of waste into the environment kills all bacteria except those resistant, decimating important bacterial ecosystems and increasing resistant bacteria.We desperately need to know exactly how much the release of antibiotic production waste leads to the feared end results mentioned above . To do this we will sample environments into which antibiotic production waste is released, and compare them to pristine environments. This will allow us to determine exactly what effect the waste has on the microbial ecosystem, does it kill all beneficial bacteria to only leave harmful resistant bacteria alive. We will carefully examine the waste to determine exactly how much active antibiotic is released but also which other potentially toxic chemicals are contained within the waste that may affect bacteria. And we will then test the ability of these chemicals to also induce resistant bacteria, as a consequence of them trying to avoid chemical killing.

抗生素是地球上最重要的药物之一。没有它们，我们就无法治疗绝大多数传染病，从危及生命的肠道感染和血流感染，到治疗使人衰弱的慢性感染，如尿路感染和呼吸道感染。抗生素是预防CF和COPD等呼吸系统疾病患者死亡所必需的，也是癌症和白血病等疾病治疗的基石，在治疗期间必须预防感染。世界上大多数抗生素都是在印度的制药厂生产的。抗生素可以通过化学合成或通过培养大量自然产生抗生素的微生物来生产。这两种方法都会产生大量的废物，其中可能含有活性抗生素和/或可能对细菌和其他细胞类型有毒的化学品。这些废物在排放到环境中之前要经过处理厂。这就产生了一个巨大的潜在问题，因为我们让细菌接触抗生素越多，它们就会越快地对药物产生耐药性，这意味着它们不能用于治疗感染。还有一种可能性是，将废物排放到环境中，除了那些具有耐药性的细菌外，杀死了所有细菌，从而摧毁了重要的细菌生态系统，增加了耐药细菌。我们迫切需要确切地知道抗生素生产废物的释放会导致上面提到的可怕的最终结果。为了做到这一点，我们将对抗生素生产废物释放的环境进行采样，并将其与原始环境进行比较。这将使我们能够确切地确定废物对微生物生态系统的影响，它是否杀死了所有有益的细菌，只留下有害的耐药细菌。我们将仔细检查废物，以确定释放了多少有效抗生素，以及废物中含有哪些可能影响细菌的其他潜在有毒化学物质。然后我们将测试这些化学物质诱导耐药细菌的能力，因为它们试图避免化学杀死。

项目成果

Multidrug resistance plasmids commonly reprogram the expression of metabolic genes in Escherichia coli

• DOI: 10.1128/msystems.01193-23
• 发表时间: 2024-02-20
• 期刊: MSYSTEMS
• 影响因子: 6.4
• 作者: Hall，Rebecca J.;Snaith，Ann E.;McNally，Alan
• 通讯作者: McNally，Alan