Role of PCF8775 antigen and its coli surface subcomponents for colonization, disease, and protective immunogenicity of enterotoxigenic Escherichia coli in rabbits

Abstract

The role of the PCF8775 antigen and its antigenic subcomponents, in particular, the coli surface (CS) antigen CS6, as colonization factors and protective antigens was studied in the reversible intestinal tie adult rabbit diarrhea model. This was done by testing the abilities of different mutants which carried one or two of the CS components to colonize the intestine and to induce protective immunity against reinfection with PCF8775positive enterotoxin-producing Escherichia coli. Infection with enterotoxigenic E. coli carrying CS4-CS6, CS5-CS6, or CS6 alone induced diarrhea in 75% or more of the rabbits, whereas the corresponding nonenterotoxigenic mutants, as well as enterotoxigenic but CS-negative strains, induced diarrhea in only a few cases. Mutants carrying CS6 alone colonized the intestine equally as well as strains carrying CS4-CS6 or CS5-CS6 did, whereas CS-negative mutants were excreted in the stool for a significantly shorter period. Rabbits previously infected with mutants carrying CS6 alone or CS6 in combination with CS4 or CS5 developed diarrhea with a significantly lower frequency after reinfection with a normally highly diarrheagenic dose of enterotoxigenic CS4-CS6-positive E. coli bacteria than did animals immunized with corresponding CS-negative mutants. Fecal excretion of the rechallenge strain was also of considerably shorter duration than that observed after initial infection with corresponding strains in 27 of the 30 animals (90%) immunized with strains carrying CS6 alone or in combination with CS4 or CS5. Such reduced shedding of the challenge strain was only seen in a few rabbits (3 of 12) initially infected with CS-negative bacteria. These results suggest that the CS6 component of PCF8775 is a colonization factor in rabbits and that it is also capable of inducing protective immunity.

Enterotoxigenic Escherichia coli in children with acute diarrhoea and controls in Teresina/PI, Brazil: distribution of enterotoxin and colonization factor genes

“…Currently, there is no licensed vaccine for use against ETEC diarrhoea. It has been demonstrated that immunization with CF-expressing ETEC strains induces protective immunity against diarrhoea in animal models and humans (Evans et al 1984;Ahren et al 1986;Svennerholm et al 1988;Oyofo et al 2001). For these reasons, CF should be taken as potential antigens to be included into a vaccine formula.…”

Crystal structure of enterotoxigenic Escherichia coli colonization factor CS6 reveals a novel type of functional assembly

“…Many ETEC strains express only CS6 or coexpress it with coli surface antigens CS4 or CS5 (Gaastra and Svennerholm, 1996;Qadri et al, 2005;Ghosal et al, 2007). For all these strains, CS6 was shown to be essential for intestine colonization (Svennerholm et al, 1988). The role of CS6 in intestinal adherence was demonstrated in vitro using bacteria only expressing CS6 and intestinal cell lines (Tobias et al, 2008;Ghosal et al, 2009).…”

The CS6 colonization factor of human enterotoxigenic Escherichia coli contains two heterologous major subunits

“…Attached bacteria can then deliver their toxin(s). It has not yet been shown that CS6 is an adhesin for human tissue [4], but a study in rabbits indicated that it is a CF [5]. Furthermore ETEC that produce only CS6 cause diarrhea in humans [3].…”