The epidemiology of transmissible antimicrobial resistance among Shigella species

志贺菌属中传播性抗菌药物耐药性的流行病学

• 批准号: MR/X000648/1
• 负责人: Kate Baker
• 金额: $ 90.62万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX000648%2F1
• 关键词: epidemiology; transmissible; antimicrobial; resistance; among

Antimicrobial drugs, such as antibiotics, antivirals and antifungals, revolutionised medicine. They are essential for fighting diseases, and make surgery and cancer therapies safer. Unfortunately, many of the microbes which these drugs fight are becoming 'resistant' and the antimicrobial drugs no longer work. Worldwide, more than 700,000 people each year die due to antimicrobial drug-resistant disease. Antimicrobial resistance (AMR) is increasing rapidly; the United Nations predicts that number of deaths due to antimicrobial drug-resistant disease may climb to as many as 10 million deaths per year by 2050 if no action is taken.Our work focuses on AMR in Shigella bacteria. Shigella are the main cause of severe diarrhoea among children in low-and middle-income countries and also cause sexually transmissible illness in men who have sex with men. Over 200 million people become ill from Shigella each year and over 200,000 people die. There is no widely available vaccine against Shigella and, like many other bacteria, they are becoming resistant to antimicrobials. The World Health Organisation list Shigella as one of twelve priority organisms for antimicrobial resistance (AMR). When bacteria reproduce, they typically divide into two daughter cells. The process by which AMR genes are passed from parent to daughter cells is well understood and monitored. However, many bacterial species are also able to transfer genes for AMR between different cells using mobile genetic elements (MGEs). This is called 'transmissible AMR' and - as the name suggests - involves direct transfer of genes between two bacteria. Our pilot work shows that about half of the AMR in Shigella is transmissible. We don't fully understand how MGEs move about in bacterial populations, but it is clear that some AMR-MGEs stay in bacteria which go on to cause lots of infections, while others don't.Understanding how AMR MGEs spread amongst bacterial populations, and which MGEs will be successful is challenging; we need to consider the AMR gene, the MGE, the bacteria, and the human hosts. Shigella is an excellent model to study transmissible AMR because Shigella infections are already tracked by national public health surveillance teams, and because it only causes infections in humans (so we don't need to consider the effects of different hosts). This means that we can use routine surveillance data to understand how the bacteria and the human hosts interact. This project will, for the first time, create a global overview of the most important Shigella bacteria in their human hosts. It will characterise all the MGEs carrying medically important AMR to understand which ones are causing the most infections and how the MGEs are moving through the bacterial populations. We will then study which types, and what features, of MGEs are the most important factors for driving this transmissible AMR in the real-world. This will enable us to understand the biology of AMR-MGEs and identify features that might act as 'early warning signs' for the emergence of new AMR bacteria. We want our research to make health systems better by identifying newly emerging AMR and understanding which groups of people are at most risk from Shigella AMR. In the future this will enable these people to be given specialised healthcare, such as screening and tailored antimicrobial recommendations. We have built a team that includes academic researchers specialising in AMR and public health specialists who are responsible for disease surveillance across four countries. This will ensure that our new findings and new approaches are useful for public health practitioners and that they will be adopted for use in real-world settings in the near term. Although this project focuses on Shigella, our new methods will be designed to make them easy to use for other bacterial species in the future.

抗生素、抗病毒药和抗真菌药等抗微生物药物彻底改变了医学。它们对于对抗疾病至关重要，并使手术和癌症治疗更加安全。不幸的是，这些药物所对抗的许多微生物正在变得“耐药”，抗菌药物不再起作用。全球每年有超过 70 万人死于抗菌药物耐药性疾病。抗生素耐药性（AMR）正在迅速增加；联合国预测，如果不采取行动，到 2050 年，每年因抗菌药物耐药性疾病导致的死亡人数可能会攀升至 1000 万人。我们的工作重点是志贺氏菌中的 AMR。志贺氏菌是低收入和中等收入国家儿童严重腹泻的主要原因，也会导致男男性行为者感染性传播疾病。每年有超过 2 亿人感染志贺氏菌，超过 20 万人死亡。目前还没有针对志贺氏菌的广泛疫苗，并且与许多其他细菌一样，志贺氏菌正在对抗菌药物产生耐药性。世界卫生组织将志贺氏菌列为抗菌素耐药性 (AMR) 的 12 种优先微生物之一。当细菌繁殖时，它们通常分裂成两个子细胞。 AMR 基因从亲代细胞传递到子代细胞的过程已被充分了解和监测。然而，许多细菌物种也能够使用移动遗传元件 (MGE) 在不同细胞之间转移 AMR 基因。这被称为“可传播的 AMR”，顾名思义，涉及两种细菌之间基因的直接转移。我们的试点工作表明，志贺氏菌中大约一半的抗菌素耐药性是可传播的。我们并不完全了解 MGE 在细菌群体中的移动方式，但很明显，一些 AMR-MGE 会留在细菌中，进而引起大量感染，而另一些则不会。了解 AMR-MGE 如何在细菌群体中传播，哪些 MGE 会取得成功是具有挑战性的；我们需要考虑 AMR 基因、MGE、细菌和人类宿主。志贺氏菌是研究传染性抗菌素耐药性的绝佳模型，因为志贺氏菌感染已被国家公共卫生监测小组跟踪，而且它只引起人类感染（因此我们不需要考虑不同宿主的影响）。这意味着我们可以使用常规监测数据来了解细菌和人类宿主如何相互作用。该项目将首次对人类宿主中最重要的志贺氏菌进行全球概述。它将描述所有携带医学上重要的 AMR 的 MGE 的特征，以了解哪些 MGE 引起最多的感染以及 MGE 如何在细菌群体中移动。然后，我们将研究 MGE 的哪些类型和哪些特征是在现实世界中驱动这种可传播 AMR 的最重要因素。这将使我们能够了解 AMR-MGE 的生物学特性，并确定可能作为新 AMR 细菌出现的“预警信号”的特征。我们希望我们的研究能够识别新出现的抗菌素耐药性并了解哪些人群最容易受到志贺氏菌抗菌素耐药性的威胁，从而改善卫生系统。将来，这将使这些人能够获得专门的医疗保健，例如筛查和量身定制的抗菌建议。我们建立了一个团队，其中包括专门研究抗菌素耐药性的学术研究人员和负责四个国家疾病监测的公共卫生专家。这将确保我们的新发现和新方法对公共卫生从业者有用，并在短期内应用于现实环境。尽管该项目的重点是志贺氏菌，但我们的新方法将旨在使它们将来易于用于其他细菌物种。