Adaptive acid tolerance response by Salmonella typhi and candidate live oral typhoid vaccine strains

The data presented here demonstrate that Salmonella typhi is capable of expressing an acid tolerance response (ATR) and that effective induction of this response (in nutrient-rich medium) occurs at pH 5.0 in anaerobic conditions. The candidate live oral S. typhi vaccine strains made by precise genetic methods and which carry auxotrophic mutations were CVD 906 (carries defined attenuating deletion mutations: delta aroC, delta aroD), CVD 908 (carries defined attenuating deletion mutations: delta aroC, delta aroD), 541Ty (carries attenuating deletion mutations: aroA, purA), and galE, Vi-negative (via) strain EX462. All generate an effective ATR. In contrast, nitrosoguanidine-derived live oral typhoid vaccine strain Ty21a only weakly expresses acid tolerance. This further demonstrates that the non-specific mutagenesis process used to produce Ty21a affects genetic loci outside the intended target genes for mutagenesis, galE and via, and further emphasizes the importance of using precise genetic techniques when developing live oral S. typhi vaccines.