In normal physiological conditions, the NaCl concentration in the human lung is between 50 to 100 mM, and in the blood it can be as high as 150 mM [34, 35]. In CF patients, the defective lung airway surface liquid has twice the NaCl concentration compared to healthy lungs [6, 34]. It has been reported that elevated salt levels causes failure of bacterial killing in CF patients [5, 6, 34]. The opportunistic infection of CF lungs is linked to
a variety of pathogens, including B. pseudomallei[7–9]. There is increasing evidence suggesting that salt concentration or osmolarity in a habitat influences the survival and pathogenicity of B. pseudomallei[10–12, 36, 37]. Thus, understanding the effect of salt stress is beneficial not only for environmental adaptation but also pathogenesis buy Dorsomorphin of the disease. To survive in a high salt environment, the bacteria can undergo adaptation by altering the regulation of gene expression. Using transcriptomic analysis, we recently discovered that B. pseudomallei responds to salt stress by modulating the transcription of specific genes . Among these are several loci associated with unknown functions, which need to be identified. Changes of B. pseudomallei transcriptome under salt stress include increasing expression of SDO . The SDO is an enzyme in the short-chain dehydrogenases/reductases/oxidoreductase family
that catalyzes the following chemical reaction: D-glucose + NAD+ = D-glucono-1,5-lactone + NADH + H+. Both NADP+ and NAD+ are usually utilized as cofactors . This study revealed the importance selleck screening library of SDO expression Farnesyltransferase during salt-stress adaptation. Based on the structural model of B. pseudomallei SDO, which consists of a NAD+
cofactor domain and catalytic triad containing Ser149, Tyr162, and Lys166 similar to Bacillus megaterium glucose 1-dehydrogenase, we hypothesized that B. pseudomallei SDO has GDH activity. To examine the function of B. pseudomallei SDO, a mutant strain lacking SDO was constructed using a gene replacement strategy, a method that rarely has a polar effect on downstream genes . In contrast to the wild type, it is clear that the B. pseudomallei SDO mutant was unable to produce GDH activity under high salt concentration. This finding is consistent with our previous observation of transcriptome profiling that B. pseudomallei grown in LB broth with 320 mM NaCl induced a 10-fold up-regulation of the SDO gene . Since the mutant lost the gene encoding for functional SDO enzyme, it was thus unable to catalyze the reaction. Several studies indicate that dehydrogenase enzymes are critical for bacterial growth. For instance, Brown & Whiteley  have shown that the gene AA02749 (lctD), encoded for an NAD+-independent L-lactate dehydrogenase, is necessary for the growth of Aggregatibacter actinomycetemcomitans. Inactivation of the AA02769 gene affects the growth of the bacteria in the presence of L-lactate.