Inhibition of phagocytosis in Yersinia pseudotuberculosis: a virulence plasmid-encoded ability involving the Yop2b protein

Abstract

Virulence plasmid-containing cells of Yersinia pseudotuberculosis had the ability to inhibit phagocytosis by mouse peritoneal macrophages cultured in vitro, but cells of its plasmid-cured derivative did not. Inhibition was most pronounced when the pathogen was incubated under Ca2-deficient conditions, which allowed a high level of expression of outer membrane proteins (Yops). The addition of 2.5 mM Ca2+ to the growth medium reduced the degree of inhibition by the pathogen, but it was still significantly higher than that of the plasmid-cured strain. An avirulent mutant strain, from which the entire yopH gene was deleted, was impaired in its phagocytosis inhibition ability. This mutant could be trans-complemented by the yopH+ gene back to the wild-type phenotype with respect to virulence, as well as the ability to inhibit phagocytosis, demonstrating that the ability to inhibit phagocytosis is an important virulence function. The mutant strain was still cytotoxic for HeLa cells, indicating that inhibition of phagocytosis can be genetically separated from the ability to cause a

Distinct mechanisms of integrin binding by Yersinia pseudotuberculosis adhesins determine the phagocytic response of host macrophages

“…Mononuclear cells and PMNs are recruited to sites of Yersinia infection in the mouse, suggesting that these cells likely play a critical role in controlling infections (Autenrieth et al, 1993). Several studies have shown that inv and yadA mutants of Y. pseudotuberculosis are comparable to parental strains in overall virulence and in their ability to colonize the spleen and liver, despite deficiencies in initial colonization of Peyer's patches and mesenteric lymph nodes (Kapperud et al, 1987;Rosqvist et al, 1988;Han and Miller, 1997;Mecsas et al, 2001). The virulence of these mutants suggests that invasin and YadA may be important for facilitating bacterial clearance not only by macrophages, but also by PMNs and dendritic cells.…”

“…(for review, see Cornelis, 2002). Nevertheless, it is estimated that these molecules are only about 50% effective in preventing uptake by host phagocytes (Rosqvist et al ., 1988). While invasin and YadA may contribute to intimate bacteria-host cell contacts that are required for Yop translocation, it is also clear that these adhesins contribute to the uptake of Yop-expressing bacteria by macrophages and polymorphonuclear cells (PMNs) (Grosdent et al ., 2002).…”

Functional analysis of the YopE GTPase-activating protein (GAP) activity of Yersinia pseudotuberculosis

“…The major virulence determinants are found on a 70 kb virulence plasmid encoding a functional type III secretion system (T3SS). Five different effector proteins, called Yops, are translocated into the target cells by the T3SS enabling the pathogen to resist the innate immune system of the host, including antiphagocytosis and downregulation of the proinflammatory cytokine response (Rosqvist et al ., 1988;Schesser et al ., 1998;Black and Bliska, 2000;Schotte et al ., 2004). One key effector in these processes is the 25 kDa YopE protein (Rosqvist et al ., 1990;Black and Bliska, 2000).…”

Target cell contact triggers expression and polarized transfer of Yersinia YopE cytotoxin into mammalian cells.

“…YpkA exhibits a Ser/Thr phosphokinase activity that shows extensive homology with corresponding enzymes of eukaryotic origin (Galyov et al, 1993). YopH and YopE obstruct the primary host defence by inhibition of phagocytosis (Rosqvist et al, 1988(Rosqvist et al, , 1990. YopH has a tyrosine phosphatase activity of eukaryotic type, suggesting that this protein acts by dephosphorylation of host structures (Guan and Dixon, 1990;Bliska et al, 1991).…”