Vi-deficient and nonfimbriated mutants of Salmonella typhi agglutinate human blood type antigens and are hyperinvasive

Abstract

We generated nonfimbriated mutants from both Vi-positive and -negative Salmonella typhi to analyze the role of type 1 fimbriae and Vi-antigen in bacterial invasion. A Vi-defective mutant of S. typhi GIFU 10007-3 was more invasive than the wild-type strain GIFU 10007. The wild-type strain expressing Vi-antigen did not agglutinate both Saccharomyces cerevisiae and human erythrocytes but Vi-defective mutants were able to agglutinate S. cerevisiae and human erythrocytes. Nonfimbriated mutants from Vi-negative GIFU 10007-3 lost the ability to adhere to S. cerevisiae but still could agglutinate human erythrocytes. The Vi-negative mutant increased secreted proteins and became 5-fold more invasive than the wild-type strain. Nonfimbriated Vi mutants became 50^120-fold more invasive than the wild-type GIFU 10007. To determine why nonfimbriated Vi mutants still agglutinate human red blood cells, we searched bacterial proteins that could bind human bloodtype antigens. We finally identified a candidate 37 kDa outer membrane protein that recognized fucosyl-galactose, a structure common to blood type A, B and H antigens. z 1998 Federation of European Microbiological Societies. Published by Elsevier Science B.V.

The Salmonella enterica serotype Typhi regulator TviA reduces interleukin-8 production in intestinal epithelial cells by repressing flagellin secretion

“…Consistent with a previous report (Miyake et al, 1998), we found that the DviaB mutant (STY2) was more invasive for T84 cells than the S. Typhi wild-type strain (Ty2) (12-fold increase) when cells were grown under conditions optimal for expression of the Vi antigen and bacterial entry was assessed using a gentamicin protection assay (Fig. 4B).…”

“…An alternative mechanism by which the viaB locus may inhibit IL-8 production is that the Vi-capsular antigen physically masks TLR ligands on the bacterial cell surface or acts as a physical barrier to their release. The finding that the Vi antigen blocks agglutination of S. Typhi with anti-LPS serum and inhibits yeast agglutination mediated by type 1 fimbriae (Miyake et al, 1998) supports the idea that the Vi capsule can physically mask surface structures. Finally, the viaB locus encodes the TviA regulatory protein that may prevent IL-8 expression in epithelial cells by altering expression of bacterial genes other than those located in the tviABCDEvexABCDE operon.…”

Host adapted serotypes of Salmonella enterica

“…These data suggest that Typhi survives and replicates within phagocytic cells of the bone marrow, spleen, and liver, but the genetic basis of this capability remains largely unknown. The expression of a capsular polysaccharide, the Vi antigen, appears to be crucial for Typhi to survive in mouse and human macrophage cell lines and to resist to lysis by serum complement [65][66][67], whereas it does not appear to be necessary for epithelial cell invasion [68]. This antigen is also known to be associated with the virulence of the organism in i o and to confer immunity against typhoid fever, when injected alone, in areas with a high incidence of this disease [69,70].…”

Vi polysaccharide–protein conjugate vaccine for the prevention of typhoid fever in children: hope or hype?

“…There has been no uniform implementation of the ViPS vaccine with a wide enough coverage and for a sufficient period of time to substantiate this theory. Additionally, while Vi-deficient strains of Salmonella typhi have been proven to be hyperinvasive in ex vivo conditions, via an increase in secreted bacterial proteins [22], the negligible incidence of typhoid fever caused by this strain suggests a decreased ability to survive once in the blood stream.…”