| 17591795 |
Kidd SP, Jiang D, Jennings MP, McEwan AG: Glutathione-dependent alcohol dehydrogenase AdhC is required for defense against nitrosative stress in Haemophilus influenzae. Infect Immun. 2007 Sep;75(9):4506-13. Epub 2007 Jun 25.
In Haemophilus influenzae Rd KW20, we identified a gene, adhC, which encodes a class III alcohol dehydrogenase (AdhC) and has S-nitrosoglutathione reductase activity. adhC exists on an operon with estD, which encodes an esterase. Divergent to the adhC-estD operon is the Haemophilus influenzae nmlR gene (nmlR (HI)), which encodes a MerR family regulator that is homologous to the Neisseria MerR-like regulator (NmlR). Analysis of an nmlR (HI) mutant indicated that expression of the adhC-estD operon is regulated by NmlR (HI) in strain Rd KW20. Chromosomal inactivation of either adhC or nmlR (HI) resulted in sensitivity to S-nitrosoglutathione and decreased S-nitrosoglutathione reductase activity. Examination of the NmlR (HI)-AdhC system in the genome sequences of nontypeable H. influenzae strains R2846, R2866, and 86-028NP identified significant variations. The adhC gene of 86-028NP was predicted to be nonfunctional due to a premature stop codon. Polymorphisms in the operator/promoter region of R2866 resulted in reduced enzyme activity. This correlated with an increased sensitivity to S-nitrosoglutathione. The adhC-nmlR (HI) system was examined in thirty-three clinical isolates (both capsular and nontypeable strains). Nucleic acid sequence data showed that only strain 86-028NP contained a premature stop codon. There were some variations in the DNA sequence of the operator/promoter region which altered the nmlR (HI) promoter. However, the clinical isolates still possessed S-nitrosoglutathione reductase activity and showed at least the equivalent ability to grow in the presence of S-nitrosoglutathione as Rd KW20. These data suggest that the nmlR (HI)-adhC system has a role in the defense against nitrosative stress in Haemophilus influenzae. |
2(0,0,0,2) |