Understanding the increasing prevalence of 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.