Mutations that confer resistance to sodium azide cause differences in the levels of two physiological isoforms of SecA.

Sodium azide inhibits bacterial growth by inhibiting the SecA-dependent translocation of proteins across the cytoplasmic membrane, and all of the mutations known to confer increased resistance to azide are in the secA gene. Nonetheless, the molecular mechanism of azide resistance is unclear. To gain insight into this mechanism, we screened for transposon insertion mutations that conferred increased resistance to sodium azide, which were unlinked to secA. We isolated six mutants, which contained insertions in the rpsA, rpsQ, srmB and nusB genes. Our results indicate that growth in the presence of azide causes accumulation of the larger of two isoforms of SecA, and the mutations caused increased production of the smaller SecA isoform in the presence of azide. In addition, mutations in secA that confer azide resistance also cause increased production of the small SecA isoform in the presence of azide. Subsequent analysis revealed that the small isoform is a truncated form of SecA that lacks the C-terminal tail. These results indicate that E. coli produces two SecA isoforms under normal growth conditions and that changes to the proportions of the isoform have physiological consequences for the cell.