Understanding the increasing prevalence of Shigella sonnei

了解宋内志贺氏菌日益流行的情况

• 批准号: MR/X00080X/1
• 负责人: Abigail Clements
• 金额: $ 69.49万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX00080X%2F1
• 关键词: Understanding; increasing; prevalence; Shigella; sonnei

Diarrheal disease remains the second leading cause of infant mortality. Shigellosis is an infection causing moderate to severe diarrhea, primarily in children under 5 years of age. There are estimated to be over 150,000 deaths attributed to shigellosis worldwide. It is mainly caused by two related bacterial species, Shigella flexneri and Shigella sonnei. Historically S. flexneri caused the vast majority of infections and it continues to cause over 60% of infections in low-income countries. S. sonnei causes approximately 25% of infections in low-income countries but can cause up to 90% of infections in middle- and high-income countries. With many large populous countries undergoing economic improvement with an expected shift to S. sonnei as the dominant cause of shigellosis (eg. China, India, Brazil) the importance of understanding how S. sonnei causes disease is critical. To date the majority of research has focussed on understanding S. flexneri infections and it was assumed that S. sonnei would use similar means to cause disease. We have recently demonstrated that S. sonnei infection is different from S. flexneri in many aspects. Importantly, unlike S. flexneri it does not invade cells efficiently. Therefore S. sonnei instead survives outside host cells where it must compete with the existing bacteria in the intestine (the microbiota) for space and food. The site of S. sonnei infection is the large intestine which contains the highest number of bacteria of any area of the body. S. sonnei has two anti-bacterial mechanisms that allow it to directly kill other bacterial species. We will investigate under what conditions and against which other bacteria S. sonnei uses these two killing mechanisms. Most easily digestible nutrients are absorbed in the small intestine and therefore nutrient utilisation is vitally important for resident and disease-causing bacteria to survive in the large intestine. We have found that S. sonnei is better able to survive starvation conditions compared to S. flexneri. As S. flexneri mainly survives and replicates inside host cells where nutrients are plentiful it has lost the ability to use a wide variety of nutrients. We will investigate how S. sonnei survives starvation and why this is different for S. flexneri.Antibiotics used to treat shigellosis are becoming less effective as antibiotic resistant bacteria arise. There are no vaccines currently available to prevent shigellosis, although many are in development. It is important to understand how these two Shigella species cause disease as this could influence how effective the vaccines are. It may also allow other prevention strategies to be considered and inform the treatment for this common infection.

腹泻病仍然是婴儿死亡的第二大原因。志贺氏菌病是一种引起中度至重度腹泻的感染，主要发生在5岁以下的儿童中。据估计，全世界有超过15万人死于志贺氏菌病。它主要由两种相关的细菌引起，福氏志贺菌和宋内志贺菌。历史上S。福氏利引起绝大多数感染，并且在低收入国家中继续引起超过60%的感染。S. Sonnei在低收入国家引起约25%的感染，但在中高收入国家可引起高达90%的感染。随着许多人口大国正在经历经济改善，预计将转向S。宋内氏菌是志贺氏菌病的主要原因（例如，中国，印度，巴西）的重要性，了解如何S。sonnei引起的疾病是至关重要的。到目前为止，大多数研究都集中在理解S。弗氏志贺菌感染，并假定S. sonnei会用类似的方法来引起疾病。我们最近证明了S。宋内氏菌感染与S.在许多方面，Flexneri。重要的是，不像S。它不能有效地侵入细胞。因此，S。相反，sonnei在宿主细胞外生存，在那里它必须与肠道中现有的细菌（微生物群）竞争空间和食物。S.宋内氏菌感染是大肠中细菌数量最多的部位。S. Sonnei具有两种抗菌机制，使其能够直接杀死其他细菌物种。我们将研究在什么条件下以及针对哪些其他细菌S。sonnei使用这两种杀人机制。大多数易消化的营养物质在小肠中被吸收，因此营养物质的利用对于大肠中的居民和致病细菌的生存至关重要。我们发现S.与S.弗莱克斯内里。作为S.弗氏杆菌主要在营养丰富的宿主细胞内生存和复制，它已经失去了利用各种营养物质的能力。我们将研究S。sonnei生存饥饿和为什么这是不同的S。用于治疗志贺氏菌病的抗生素随着抗生素抗性细菌的出现而变得不那么有效。目前没有预防志贺氏菌病的疫苗，尽管许多疫苗正在开发中。重要的是要了解这两种志贺氏菌是如何引起疾病的，因为这可能会影响疫苗的有效性。它还可以允许考虑其他预防策略，并为这种常见感染的治疗提供信息。