Nuclear Factor Kappa B-dependent Persistence of Typhi and Paratyphi in Human Macrophages

Importance: Salmonella enterica is a common cause of gastrointestinal infections worldwide. The serovars Typhi and Paratyphi A cause a distinctive systemic illness called enteric fever, whose pathogenesis is incompletely understood. Here, we show that enteric fever serovars lack 12 specific virulence factors possessed by nontyphoidal serovars, which allow the enteric fever serovars to persist within human macrophages. We propose that this fundamental difference in the interaction of 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.