ADAPTIVE ACID TOLERANCE RESPONSE BY SALMONELLA-TYPHI AND CANDIDATE LIVE ORAL TYPHOID VACCINE STRAINS

The data presented here demonstrate that Salmonella typhi is capable o f expressing an acid tolerance response (ATR) and that effective induc tion of this response (in nutrient-rich medium) occurs at pH 5.0 in an aerobic conditions. The candidate live oral S. typhi vaccine strains m ade by precise genetic methods and which carry auxotrophic mutations w ere CVD 906 (carries defined attenuating deletion mutations. Delta aro C, Delta aroD), CVD 908 (carries defined attenuating deletion mutation s. Delta aroC, Delta aroD), 541Ty (carries attenuating deletion mutati ons: aroA, purA), and galE, Vi-negative (via) strain EX462. All genera te an effective ATR. In contrast, nitrosoguanidine-derived live oral t yphoid vaccine strain Ty21a only weakly expresses acid tolerance. This further demonstrates that the non-specific mutagenesis process used t o 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.