Flagellar phase variation of Salmonella enterica serovar typhimurium contributes to virulence in the murine typhoid infection model but does not influence Salmonella-induced enteropathogenesis
Js. Ikeda et al., Flagellar phase variation of Salmonella enterica serovar typhimurium contributes to virulence in the murine typhoid infection model but does not influence Salmonella-induced enteropathogenesis, INFEC IMMUN, 69(5), 2001, pp. 3021-3030
Although Salmonella enterica serovar Typhimurium can undergo phase variatio
n to alternately express two different types of flagellin subunit proteins,
FljB or FliC, no biological function for this phenomenon has been describe
d. In this investigation, we constructed phase-lacked derivatives of S, ent
erica serovar Typhimurium that expressed only FljB (termed locked-ON) or Fl
iC (termed locked-OFF). The role of phase variation in models of enteric an
d systemic pathogenesis was then evaluated. There were no differences betwe
en the wild-type parent strain and the two phase-locked derivatives in adhe
rence and invasion of mouse epithelial cells in vitro, survival in mouse pe
ritoneal macrophages, or in a bovine model of gastroenteritis. By contrast,
the locked-OFF mutant was virulent in mice following oral or intravenous (
i.v.) inoculation but the locked-ON mutant was attenuated. When these phase
-locked mutants were compared in studies of i.v. kinetics in mice, similar
numbers of the two strains were isolated from the blood and spleens of infe
cted animals at 6 and 24 h. However, the locked-OFF mutant was recovered fr
om the blood and spleens in significantly greater numbers than the locked-O
N strain by day 2 of infection. By 5 days postinfection, a majority of the
mice infected with the locked-OFF mutant had died compared,with none of the
mice infected with the locked-ON mutant. These results suggest that phase
variation is not involved in the intestinal stage of infection but that onc
e S. enterica serovar Typhimurium reaches the spleens of susceptible mice t
hose organisms in the FliC phase can grow and/or survive better than those
in the FljB phase, Additional experiments with wild-type S. enterica serova
r Typhimurium, fully capable of switching flagellin type, supported this hy
pothesis. We conclude that organisms that have switched to the FliC(+) phas
e have a selective advantage in the mouse model of typhoid fever but have n
o such advantage in invasion of epithelial cells or the induction of entero
pathogenesis.