| Summary: | <i>Salmonella</i> Enteritidis (SE) can spread from the intestines to cause systemic infection, mainly involving macrophages. Intramacrophage <i>Salmonella</i> exits and reinfects neighboring cells, leading to severe disease. <i>Salmonella</i> genes involved in exiting from macrophages are not well understood or fully identified. A <i>focA::</i>Tn5 mutant was identified by an in vitro assay, with increased ability to exit from macrophages. A defined SEΔ<i>focA</i> mutant and its complemented derivative strain, SEΔ<i>focA</i>::<i>focA</i>, were constructed to confirm this phenotype. Although the lethal ability of <i>focA</i> mutants was similar to that of the parental SE in mice, it was isolated earlier from the liver and spleen than the parental SE. <i>focA</i> mutants induced higher levels of proinflammatory IL-12 and TNF-α compared with the parental SE and SEΔ<i>focA</i>::<i>focA</i>. <i>focA</i> mutants showed higher cytotoxicity and lower formate concentrations than SE and SEΔ<i>focA</i>::<i>focA</i>, whereas there was no change in pyroptosis, apoptosis and flagella formation ability. These current data suggest that the <i>focA</i> gene plays an important role in regulating intramacrophage <i>Salmonella</i> exiting and extraintestinal spread in mice, although the specific mechanism requires further in-depth studies.
|
|---|