[Virulence factors of Salmonella: from molecular genetics to diagnostic applications]

Salmonella serotype Typhimurium is a facultative intracellular pathogen that causes a systemic infection in naturally, or experimentally, infected mice. After oral contamination, Typhimurium colonizes the ileal mucosa and Peyer's patches and invades draining mesenteric lymph nodes. From these primary sites of infection, bacteria dissiminate to the reticuloendothelial system and proliferate rapidly in spleen and liver. Several virulence factors are encoded by chromosomal genes. The ability of Typhimurium to adhere to and invade epithelial cells has been associated with flagella, pili of type I and mannose-resistant haemagglutinating activity. By comparing the virulence of isogenic strains, it appeared that these traits played a marginal role and were not essential for full virulence expression. It is now clear that other surface structures are important for the invasiness capacity of Typhimurium. To multiply in the reticuloendothelial system, a complete lipopolysaccharide is necessary for the bacteria in resisting serum bactericidal activity and producing tissue damage. Salmonella have evolved a specialized iron-binding ligand, termed enterobactin, to acquire iron necessary for their multiplication. Enterobactin competes with the host iron-binding proteins (transferrin or lactoferrin) to secure the iron required by the bacteria. Though the presence of an enterotoxin in Salmonella is still controversial, there is now substantial evidence to support this concept. Recently, a gene encoding an enterotoxin has been cloned from Typhimurium and expressed in E. coli. Typhimurium strains harbour a 90 kilobases (kb) plasmid which is essential for virulence. This plasmid encodes virulence factors required for replication of Salmonella in liver and spleen. It was postulated that the plasmid allowed Typhimurium to multiply in Kupffer cells and in splenic macrophages. The virulence-associated region of the plasmid restored full virulence to plasmidless strains. Transposon insertion mutagenesis demonstrated the existence of two DNA sequences, designated Vir A and Vir B, which are essential for virulence expression. The Vir A region has been sequenced; it encodes four polypeptides with apparent molecular mass of 27,000, 28,000, 33,000 and 70,000. The Vir B region encodes two polypeptides of 38,000 and 43,000. In an attempt to identify bacterial components contributing to invasion of HeLa cells by Salmonella serovar Typhi, we cloned a 30 kb DNA sequence necessary for entry of bacteria into epithelial cells. However, this sequence is not sufficient for conferring an invasive phenotype to E. coli strains. From this DNA fragment, a short segment of 487 bp was subcloned, sequenced and used as probe to detect Salmonella.(ABSTRACT TRUNCATED AT 400 WORDS)