Figure 3. Aromatic substitutions at position 12 retain SsrB pH sensitivity.
(a) Normalized PsifA-lacZ activity in the presence of SsrB or H12 mutants of SsrB grown in magnesium minimal medium (MGM) pH 7.4 (blue bars) and pH 5.6 (red bars) after 3 hr of 0.1% (w/v) arabinose induction. The H12K, H12Y, and H12F substitutions showed a decrease in activity at pH 7.4 compared to SsrB (34 ± 4%, 30 ± 4%, and 24 ± 8%). (b) SsrB H12K only showed a moderate increase in activity at pH 5.6 (2.7-fold); however, the SsrB H12Y and H12F substitutions retained an acid-stimulated increase in the activity (6.9- and 6.7-fold, respectively) comparable to the wild-type (5-fold). (c) PsifA-lacZ activity measured from strains recovered at 8 hr post HeLa infection. The activity of the SsrB H12Q and SsrB H12Y-expressing strains was 62 ± 12% and 58 ± 3%, respectively, relative to the SsrB-expressing strain (p<0.001, n = 3). (d) Intracellular survival of strains in HeLa cells at 16 hr post infection (hpi). During HeLa cell infection, the c.f.u./ml of the SsrB-expressing strain increased 19-fold at 16 hpi. For SsrB H12Q and SsrB H12Y-expressing strains, the c.f.u./ml only increased 6.4- and 7.6-fold, respectively (p<0.0001, n = 3).