Diarrhoeal diseases are the most common illnesses resulting from the consumption of unsafe food and water. It is estimated that 550 million people contract such a disease each year, 220 million of whom are children under the age of five years^[1]. Salmonella^[2] and Shigella^[3] are among the most common pathogens responsible. They are present everywhere, in water, soil and the food chain. Outbreaks of salmonellosis are very common, including in Western countries. Shigellosis, characterized by bloody diarrhoea, is endemic in many countries and regularly causes epidemics with high mortality. Food hygiene and sanitary rules are part of the preventive measures recommended by the World Health Organization. However, these rules are not always easy to implement in regions with a difficult socio-economic context. The treatments currently available are symptomatic (rehydration solutions). The emergence of antibiotic resistance in these bacteria makes antibiotic treatment difficult, and the existence of many serovars (subspecies) of these pathogens limits the development of effective vaccines. Vaccines exist against some Salmonella serovars (which cause typhoid fever) but do not work against another invasive non-typhoid serovar, which is the majority in Africa. The situation is even worse for Shigella, for which no vaccine is currently licensed.

With a view to developing broad-spectrum vaccines capable of simultaneously protecting against these two bacterial pathogens, researchers at SPI/LERI have focused on the system that allows Salmonella and Shigella to inject their virulence factors through the plasma membrane of host cells. Their XXS-size "syringe", called type III secretion system or injectisome, is very similar. In particular, the injection needle cap proteins (SipD for Salmonella and IpaD for Shigella) have quite similar assembly mechanisms and three-dimensional structures, despite relatively weak sequence identity (38%). Moreover, their protective efficacy against each of the bacterial genera has already been demonstrated in rodents. These elements led the researchers to consider the possibility of obtaining cross-protection against Salmonella and Shigella using SipD or IpaD as immunogens. The team administered each of the two proteins, alone, by intranasal or intragastric routes in a mouse model of intestinal infection. Strong humoral responses (production of immunoglobulins G and A) were induced against both proteins regardless of the route of administration. In addition, mice immunized with SipD or IpaD were protected against infection by Salmonella enterica (serovar Typhimurium) or Shigella flexneri. The study thus shows that cross-protection against Salmonella - Shigella is possible and paves the way for the development of broad-spectrum therapeutic molecules. 

Contact: 

Stéphanie Simon (stephanie.simon@cea.fr)

[1] Source: World Health Organization
[2] There are two species of Salmonella: Salmonella enterica (some serovars are responsible for typhoid fever) and Salmonella bongori, with more than 2000 different serovars.
[3] There are four species of Shigella: Shigella flexneri, Shigella sonnei, Shigella dysenteriae and Shigella boydii.