Understanding the increasing prevalence of Shigella sonnei

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，即福氏志贺氏菌和索尼氏志贺氏菌。从历史上看，绝大多数感染是由弗氏杆菌引起的，在低收入国家，它继续导致60%以上的感染。在低收入国家，约25%的感染是由索内氏杆菌引起的，但在中等收入和高收入国家，可导致高达90%的感染。许多人口大国正在经历经济改善，预计索尼氏沙门氏菌将成为志贺氏菌病的主要病因。（中国、印度、巴西）了解索内沙门氏菌如何致病的重要性至关重要。迄今为止，大多数研究都集中在理解弗氏沙门氏菌感染上，并假设索内沙门氏菌会使用类似的方法引起疾病。我们最近证明了索内沙门氏菌感染在许多方面与弗氏沙门氏菌不同。重要的是，与S. flexneri不同，它不能有效地侵入细胞。因此，sonnei在宿主细胞外生存，在那里它必须与肠道内现有的细菌（微生物群）竞争空间和食物。sonnei链球菌感染的部位是大肠，它是人体任何部位中细菌数量最多的。sonnei有两种抗菌机制，可以直接杀死其他细菌。我们将研究在什么条件下以及针对哪些其他细菌sonnei使用这两种杀伤机制。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常驻细菌和致病细菌在大肠中生存至关重要。我们发现sonnei比S. flexneri更能在饥饿条件下生存。由于flexneri主要在营养丰富的宿主细胞内存活和复制，因此失去了使用多种营养物质的能力。我们将研究sonnei如何在饥饿中存活，以及为什么这与S. flexneri不同。随着耐药细菌的出现，用于治疗志贺氏菌病的抗生素正变得越来越无效。目前还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，因为这可能影响疫苗的有效性。它还可以考虑其他预防策略，并为这种常见感染的治疗提供信息。

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.