ListeriaPathogenesis and Molecular Virulence Determinants

Abstract

The gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a highly fatal opportunistic foodborne infection. Pregnant women, neonates, the elderly, and debilitated or immunocompromised patients in general are predominantly affected, although the disease can also develop in normal individuals. Clinical manifestations of invasive listeriosis are usually severe and include abortion, sepsis, and meningoencephalitis. Listeriosis can also manifest as a febrile gastroenteritis syndrome. In addition to humans, L. monocytogenes affects many vertebrate species, including birds. Listeria ivanovii, a second pathogenic species of the genus, is specific for ruminants. Our current view of the pathophysiology of listeriosis derives largely from studies with the mouse infection model. Pathogenic listeriae 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-mediated immune response. This initial, subclinical step of listeriosis is thought to be common due to the frequent presence of pathogenic L. monocytogenes in food. In normal indivuals, the continual exposure to listerial antigens probably contributes to the maintenance of anti-Listeria memory T cells. However, in debilitated and immunocompromised patients, the unrestricted proliferation of listeriae in the liver may result in prolonged low-level bacteremia, leading to invasion of the preferred secondary target organs (the brain and the gravid uterus) and to overt clinical disease. L. monocytogenes and L. ivanovii are facultative intracellular parasites able to survive in macrophages and to invade a variety of normally nonphagocytic cells, such as epithelial cells, hepatocytes, and endothelial cells. In all these cell types, pathogenic listeriae go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. In this way, listeriae disseminate in host tissues sheltered from the humoral arm of the immune system. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review describes in detail the molecular determinants of Listeria virulence and their mechanism of action and summarizes the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listeria infection. This article provides an updated perspective of the development of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start of the genomic era of Listeria research

Recent advances in the immunobiology of ceramide

“…Sphingomyelinases (SMases) catalyze the hydrolysis of sphingomyelin (ceramidephosphorylcholine) into ceramide and phosphorylcholine (Levade and Jaffrezou, 1999). SMases have been characterized as acid SMase, secretory SMase, neutral Mg 2+ dependent SMase, Mg 2+ independent neutral SMase, alkaline SMase and bacterial SMase-phospholipase C. Acid SMase deficiency has been implicated in the Niemann-Pick syndrome, secretory SMase in atherogenesis, neutral Mg 2+ dependent SMase in atherosclerosis and apoptosis and alkaline SMase in colon carcinogenesis (Samet and Barenholz, 1999;Tabas, 1999;Chatterjee, 1999;Ghosh et al, 1998;Nilsson and Duan, 1999;Vazquez-Boland et al, 2001). Ceramide is generated from sphingomyelin located in the outer layer of plasma membrane by neutral Mg 2+ dependent sphingomyelinase while same ceramide are formed from sphingomyelin in endo/lysosomes by acid SMase.…”

Gene Scanning of an Internalin B Gene Fragment Using High-Resolution Melting Curve Analysis as a Tool for Rapid Typing of Listeria monocytogenes

“…The high case-fatality proportion of approximately 20% to 30% makes L. monocytogenes an important human pathogen. [1][2][3] In listeriosis outbreaks and for epidemiological investigations, a fast and accurate protocol for subtyping L. monocytogenes is essential. 4 In outbreak situations the L. monocytogenes serotyping scheme based on somatic (O) and flagellar (H) antigens 5 has limited value for tracking isolates.…”

Infecção natural por Listeria monocytogenes em cobaios Cavia porcellus

“…A infecção hepática é explicada pela passagem intestinal da bactéria (VÁZQUEZ-BOLAND et al, 2001), que, nos casos estudados, pode estar associada com a ingestão da casca de arroz utilizada como cama nas gaiolas, ou alimento contaminado pelo contato com a cama. Dois cobaios (3 e 4) apresentaram broncopneumonia supurativa associada com reações positivas na imuno-histoquímica anti Listeria monocytogenes, mas sem alterações significativas em outros órgãos.…”