Proton gradient drives salmonella infection
New insights into the workings of the type III secretion system of salmonellae
Salmonellae are some of the most common bacterial pathogens causing gastrointestinal inflammations. To infect humans, the bacteria use a sophisticated strategy: They get close to the host cell and dock on to it and then they inject signal substances allowing them to enter the cell. Scientists of the Helmholtz Centre for Infection Research (HZI) in Braunschweig just showed how the release of these signal substances and therefore the infection process is facilitated. The researchers published their results in the professional magazine, "PLOS Genetics".
Contaminated eggs, sweet desserts and uncooked poultry products are amongst the most common causes of salmonella infections. This can cause severe intestinal inflammation, possibly with fatal consequences, especially in small children and elderly people. The bacteria are taken up into the body with the food and then move actively to the intestinal cells by means of a rotating flagellum. Once they arrive there, the salmonellae use the so-called needle complex to infect the host: They dock on to the cell and inject toxic substances using a molecular needle. This process allows the bacteria to infect the host cell and to survive and proliferate inside the host cell.
A so-called type III secretion system is of crucial importance for injection of the toxins by the needle complex and for the assembly of the flagellum. Scientists used to presume that the ATPase bound to the base of the needle complex and flagellum was essential to the function of the type III secretion system. ATPases are enzymes that promote a chemical reaction that releases energy. This energy can then be used to drive other reactions - such as the release of toxins in the present case. "We just showed for the first time that the system also works when the ATPase is not present," says Dr Marc Erhardt, head of the junior research group, "Infection biology of Salmonellae", at the HZI. "Only the proton gradient appears to be absolutely required, whereas the ATPase has more of a supporting role." The enzyme increases the efficiency of the system, but is not indispensable for its function.
Firstly, this insight helps researchers to better understand the molecular mechanisms of the secretion system. This is important, mainly, because the type III secretion system is used not only by salmonellae, but also by numerous other gram-negative bacteria, to infect host cells. An understanding of the infection process on the molecular level allows the scientists to manipulate this process in specific ways in the future. "It is therefore a very good starting point for novel therapies against gram-negative bacteria," says Erhardt.
But the discovery is interesting not only from a medical point of view, but for its evolutionary perspective as well. After all, the bacterial flagellum is often cited by the "Intelligent Design" movement as an example of a system that cannot have developed by evolution due to its rich complexity. However, the insights just gained indicate that the ATPase has become added to an ancestral proton-driven type III secretion system in order to make the secretion process more efficient. This was an evolutionary advantage for the bacteria. "This is proof that even a nano-machine as complex as the flagellum can be sub-divided into less complex, but fully functional sub-units and therefore contradicts the notions of the "Intelligent Design" movement," says Erhardt.
ATPase-independent type-III protein secretion in Salmonella enteric, Marc Erhardt, Max E. Mertens, Florian D. Fabiani, and Kelly T. Hughes, Plos Genetics, DOI: pgen.1004800.
The "Infection Biology of Salmonella" junior research group at the HZI investigates the strategy of attack used by these bacteria – to develop novel strategies against bacterial infections.
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