Nuclear factor kappa B-dependent persistence of <i>Salmonella</i> Typhi and Paratyphi in human macrophages

Abstract

Salmonella enterica is a common cause of gastrointestinal infections worldwide. The serovars <i>Salmonella</i> Typhi and <i>Salmonella</i> Paratyphi A cause a distinctive systemic illness called enteric fever, whose pathogenesis is incompletely understood. Here, we show that enteric fever <i>Salmonella</i> serovars lack 12 specific virulence factors possessed by nontyphoidal <i>Salmonella</i> serovars, which allow the enteric fever serovars to persist within human macrophages. We propose that this fundamental difference in the interaction of <i>Salmonella</i> with human macrophages is responsible for the chronicity of typhoid and paratyphoid fever, suggesting that targeting the nuclear factor κB (NF-κB) complex responsible for macrophage survival could facilitate the clearance of persistent bacterial infections.