Listeria pathogenesis and molecular virulence determinants

Ja. Vazquez-boland et al., Listeria pathogenesis and molecular virulence determinants, CLIN MICROB, 14(3), 2001, pp. 584
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Categorie Soggetti
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0893-8512 → ACNP
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The gram-positive bacterium Listeria monocytogenes is the causative agent o f listeriosis, a highly fatal opportunistic foodborne infection. Pregnant w omen, neonates, the elderly, and debilitated or immunocompromised patients in general are predominantly affected, although the disease can also develo p in normal individuals. Clinical manifestations of invasive listeriosis ar e usually severe and include abortion sepsis, and meningoencephalitis. List eriosis can also manifest as a febrile gastroenteritis syndrome. Zn additio n to humans, L. monocytogenes affects many vertebrate species, including bi rds. Listeria ivanovii, a second pathogenic species of the genus, is specif ic for ruminants. Our current view of the pathophysiology of listeriosis de rives largely from studies with the mouse infection model Pathogenic lister iae enter the host primarily through the intestine. The liver is thought to be their first target organ after intestinal translocation. In the liver, listeriae actively multiply until the infection is controlled by a cell-med iated immune response. This initial subclinical step of listeriosis is thou ght to be common dire to the frequent presence of pathogenic L. monocytogen es in food In normal indivuals the continual exposure to listerial antigens probably contributes to the maintenance of anti-Listeria memory T cells. H owever; in debilitated and immunocompromised patients, tile unrestricted pr oliferation of listeriae in the liver may result in prolonged low-level bac teremia, leading to invasion of the preferred secondary target organs (the brain and the gravid uterus) and to overt clinical disease. L. monocytogene s and L. ivanovii are facultative intracellular parasites able to survive i n macrophages and to invade a variety of normally nonphagocytic cells, such as epithelial cells, hepatocytes, and endothelial cells. In all these cell types, pathogenic listeria go through an intracellular life cycle involvin g early escape from the phagocytic vacuole, rapid intracytoplasmic multipli cation, bacterially induced actin-based motility, and direct spread to neig hboring cells, in which they reinitiate the cycle. In this way, listeriae d isseminate in host tissues sheltered from the humoral arm of the immune sys tem. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review de scribes in detail the molecular determinants of Listeria virulence and thei r mechanism of action and summarizes the current knowledge on the pathophys iology of listeriosis and the cell biology and host cell responses to Liste ria infection. This article provides an updated perspective of the developm ent of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start o f the genomic era of Listeria research.