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Listeria monocytogenes, how can a relatively innocuous food-borne pathogen induce a potentially fatal disease? (04/2004)
Listeria monocytogenes (L. monocytogenes) provokes listeriosis, a potentially fatal food-borne disease, which mainly affects pregnant women and immuno-compromised individuals where it can lead to death rate as high as 30%. Understanding the mechanism behind the disease is crucial to dealing with this serious health problem.
In the latest Journal of Cell Science1, scientists describe how two mammalian proteins, myosin VIIa and vezatin, are hijacked by L. monocytogenes and used in the propagation of the infection within the host. This is a particularly important discovery because in listeriosis, it is the spreading of the infection from the digestive system (the bacteria’s entrance door) to the rest of the body that leads to the more serious or even life-threatening complications of the disease.
In fact, although the infection starts in the digestive system, in more susceptible individuals, it can spread throughout the individual, into the brain or even to unborn foetuses. It is the bacteria’s capacity to cross, initially the intestinal wall and later the brain barrier and/or the placenta, three body barriers normally capable of withholding the invasion of infectious agents, that allows the spread of listeriosis and makes it such a big threat to the host.
But how does L. monocytogenes do this? Normally, bacteria or any other type of invaders as soon as they are recognised as “strangers” within the body and thus a potential danger, are engulfed and killed by specialised cells. L. monocytogenes, however, like other pathogens, has evolved a mechanism of escape, in this case by inducing its own internalisation into the host’s cells hiding away from the immune system (the body’s “police”). In the invaded cells, the bacteria can not only survive and multiply but also move throughout the body spreading the infection. It is also through this “forced” entrance that L. monocytogenes seems to be capable of crossing the intestinal, the blood-brain and the feto-placental barriers.
Comprehension of how Listeria monocytogenes invades mammalian cells during infection is vital to understand how this food-borne disease can change from inducing gastroenteritis to much more serious complications like meningitis, meningo-encephalitis, septicaemia, abortion, perinatal infection or death. Although previous work has identified the receptors involved in the interaction between Listeria and the host cells the driving force behind the internalisation of the bacteria has remained more elusive.
But now, Sandra Sousa, Didier Cabanes, Marc Lecuit, Pascale Cossart and colleagues at the Unité des Interactions Bactéries-Cellules and the Unité de Génétique des Déficits Sensoriels at the Institut Pasteur, Paris, France, report two proteins of the infected host - myosin VIIa and vezatin – which might explain how L. monocytogenes “pushes” itself into the host cells. In fact, the team of scientists describe how disruption in the function of any of these two host proteins leads to an immediate reduction in the number of infected cells, indicating that myosin VIIa and vezatin are crucial for Listeria’s cell invasion. The team of scientists also report that both these proteins are recruited to the site of the bacteria’s entrance during its internalisation.
Myosin VIIa is a motor-protein, a type of protein characterised by its ability to use the cell’s energy to create a force/tension that can then be employed, for example, to create movement within the cell. This might be the passage of a molecule across the cell membrane or the movement of a muscle. Very recently, myosin VIIa, together with vezatin, has also been found on the cell membrane where they were implicated in the mechanism responsible for maintaining cells adhered together forming tissues, such as the skin
These observations together with the results from their own experiments, led Sousa, Cossart and colleagues to propose that the mechanism of Listeria internalisation depends on highjacking the host’s myosin VIIa and vezatin and using them to create the force that “pushes” the bacteria into the cells
Sousa, Cossart and colleagues also report high levels of myosin VIIa in enterocytes, a cell type crucial for the passage of Listeria across the intestinal barrier. This led the team of scientists to further propose that the bacteria’s capacity of crossing that first body barrier, the crucial step into a widespread, and consequently much more complicated type of infection, is also dependent on the pair myosin VIIa/vezatin.
In a world where the number of immuno-compromised individuals is on the rise, especially with the advance of the AIDS epidemic in places like Africa, “opportunist” bacteria like L. monocytogenes are a serious health problem. Sousa and Cossart’s work, by helping to elucidate the mechanism behind listeriosis infection, is, without doubt, extremely important.
1 Journal of Cell Science (2004); Vol. 117, pp. 2121-2130 “Unconventional myosin VIIa and vezatin, two proteins crucial for Listeria entry into epithelial cells”
Original paper’s authors
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In collaboration with the Observatório da Ciência e do Ensino Superior (OCES)
Financed by the Fundação para a Ciência e Tecnologia (FCT) |
