Phase variation of the Ipf operon is a mechanism to evade cross-immunity between Salmonella serotypes

Conventional wisdom holds that phase variation is a mechanism for immune evasion. However, despite fimbrial phase variation, mice previously exposed to Salmonella typhimurium are protected against a subsequent challenge. We evaluated whether Ipf phase variation instead may be a mechanism to evade cross-immunity between Salmonella serotypes. Mice were immunized orally with S. typhimurium aroA mutants either that expressed the Ipf operon (phase-on variant) or in which the entire Ipf operon had been removed by deletion. During a subsequent challenge with virulent Salmonella enteritidis a selection against Ipf phase-on variants was observed in mice previously exposed to 5. typhimurium long polar fimbriae. Vaccination with S, typhimurium did not confer protection against challenge with 5. enteritidis, presumably because Ipf phase-off variants were able to evade cross-immunity. We propose that lpf phase variation is a mechanism to evade cross-immunity between Salmonella serotypes, thereby allowing their coexistence in a host population.