Salmonella enterica serovar Typhi genomic regions involved in low pH resistance and in invasion and replication in human macrophages

Salmonella enterica serovar Typhi, the etiological agent of typhoid fever, causes a systemic life-threatening disease. To carry out a successful infection process, this bacterium needs to survive alkaline and acid pH conditions presented in the mouth, stomach, small intestine, and gallbladder. Therefore, in this work, a genetic screening to identify S. Typhi genes involved in acid and circumneutral pH resistance was performed. A collection of S. Typhi mutants deleted of fragments ranging from 6 to 80 kb were obtained by the Datsenko and Wanner method. Bacterial growth rate assays of each mutant were performed to identify S. Typhi genes involved in circumneutral and acid pH resistance. S. Typhi mutants deficient to growth at specific pH were evaluated in their capacity to invade and replicate in phagocytic cells. In this work, it is reported that S. Typhi ∆F4 (pH 4.5), S. Typhi ∆F44 (pH 4.5, 5.5, and 6.5), and S. Typhi ∆F73 (pH 4.5, 5.5, 6.5, and 7.5) were deficient to grow in the pH indicated. These three mutant strains were also affected in their ability to invade and replicate in human macrophages. S. Typhi contains defined genomic regions that influence the survival at specific pH values, as well as the invasion and replication inside human cells. Thus, this genetic information probably allows the bacteria to survive in different human compartments for an efficient infection cycle.