Type III secretion machines and the pathogenesis of enteric infections caused by Yersinia and Salmonella spp.

Abstract

Salmonella and Yersinia spp. infect the intestinal tract of humans. Although these organisms cause fundamentally different diseases, each pathogen relies on type III secretion machines to either inject virulence factors into the cytosol of eukaryotic cells or release toxins into the extracellular milieu. Type III secretion machines are composed of many different subunits and export several polypeptides with unique substrate requirements. During Salmonella pathogenesis, the type III machine encoded by the Salmonella pathogenicity island (SPI)-1 genetic element functions to cause invasion of the intestinal epithelium, whereas another type III machine (SPI-2) is required for survival in macrophages. Yersinia enterocolitica and Yersinia pseudotuberculosis employ type III machines to resist macrophage phagocytosis and to manipulate the host's immune response, thereby colonizing intestinal lymphoid tissues. We describe what is known about the pathogenic functions of virulence factors secreted by type III machines. Furthermore, type III secretion machines may be exploited for the injection of recombinant proteins, a strategy that has already been successfully employed to elicit a cell-mediated immune response.

Yersinia enterocolitica TyeA, an Intracellular Regulator of the Type III Machinery, Is Required for Specific Targeting of YopE, YopH, YopM, and YopN into the Cytosol of Eukaryotic Cells

“…HeLa cells and adherent bacteria were extracted with digitonin, a detergent known to disrupt the cholesterol-containing plasma membrane of HeLa cells but not the bacterial envelope (23). Digitonin extracts were centrifuged to sediment bacteria as well as HeLa cell debris (P), while the soluble contents of the eukaryotic cytosol remained in the supernatant (S) (24). Proteins in all fractions were precipitated with chloroform-methanol and analyzed by immunoblotting with antisera raised against purified proteins (Fig.…”

Multiple Roles of CLAN (Caspase-Associated Recruitment Domain, Leucine-Rich Repeat, and NAIP CIIA HET-E, and TP1-Containing Protein) in the Mammalian Innate Immune Response

“…Bacteria such as Salmonella produce several virulence proteins associated with type III secretion systems that enable these microorganisms to subvert host antibacterial processes in the cytosol of phagocytes (40,41). Another hypothesized benefit of residing within the macrophage is that these host cells carry organisms through the lymph and blood to other tissues, thus facilitating their in vivo dissemination (42,43).…”

Pathogen-induced apoptosis of macrophages: a common end for different pathogenic strategies. Microreview

“…Genes required for Salmonella virulence are clustered into several pathogenicity islands throughout the bacterial chromosome . Two of these pathogenicity islands, designated SPI-1 and SPI-2, encode their own type III secretion systems that are each responsible for secreting a unique set of virulence proteins (reviewed by Lee and Schneewind, 1999). Current evidence indicates that genes in SPI-1 encode factors necessary for the invasion of Salmonella into the intestinal epithelium at early points during the infection (Gala  n, 1996).…”