Listeria pathogenesis and molecular virulence determinants

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

Genetic analysis of Leishmania parasites in Ecuador : are Leishmania (Viannia) panamensis and Leishmania (V.) guyanensis distinct taxa ?

In the course of an epidemiologic survey in Ecuador, the following collection of #Leishmania stocks was isolated : 28 from patients with clinical signs of leishmaniasis, 2 from sloths, 1 from a dog, and 4 from sand flies. For genetic characterization of these stocks, multilocus enzyme electrophoresis (MLEE) and random amplified polymorphic DNA (RAPD) were used. Twenty six of the 35 stocks were identified as either #Leishmania (V.) panamensis or #L. (V.) guyanensis, 2 stocks were identified as #L. (V.) braziliensis, the 2 stocks from sloths showed specific genotypes, and 5 stocks were characterized as hybrids between #L. (V.) braziliensis and #L. (V.) guyanensis. These data show that genetic diversity of #Leishmania in Ecuador is high and that #L. (V.) panamensis/#guyanensis is the dominant group in this country. The genetic analysis questioned the distinctness between the two species #L. (V.) panamensis and #L. (V.) guyanensis, since MLEE and RAPD data did not indicate that #L. (V.) panamensis and #L. (V.) guyanensis correspond to distinct monophyletic lines. Population genetic analysis performed on the #L. (V.) panamensis/#guyanensis$ group favors the hypothesis of a basically clonal population structure. (Résumé d'auteur

Staphylococcus caprae Strains Carry Determinants Known To Be Involved in Pathogenicity: a Gene Encoding an Autolysin-Binding Fibronectin and the ica Operon Involved in Biofilm Formation

The atlC gene (1,485 bp), encoding an autolysin which binds fibronectin, and the ica operon, involved in biofilm formation, were isolated from the chromosome of an infectious isolate of Staphylococcus caprae and sequenced. AtlC (155 kDa) is similar to the staphylococcal autolysins Atl, AtlE, Aas (48 to 72% amino acid identity) and contains a putative signal peptide of 29 amino acids and two enzymatic centers (N-acetylmuramoyl-l-alanine amidase and endo-β-N-acetylglucosaminidase) interconnected by three imperfect fibronectin-binding repeats. The glycine-tryptophan (GW) motif found in the central and end part of each repeat may serve for cell surface anchoring of AtlC as they do in Listeria monocytogenes. The S. caprae ica operon contains four genes closely related to S. epidermidis and S. aureus icaA, icaB, icaC, and icaD genes (≥ 68% similarity) and is preceded by a gene similar to icaR (≥70% similarity). The polypeptides deduced from the S. caprae ica genes exhibit 67 to 88% amino acid identity to those of S. epidermidis and S. aureus ica genes. The ica operon and icaR gene were analyzed in 14 S. caprae strains from human specimens or goats' milk. Some of the strains produced biofilm, and others did not. All strains carry the ica operon and icaR of the same sizes and in the same relative positions, suggesting that the absence of biofilm formation is not related to the insertion of a mobile element such as an insertion sequence or a transposon