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Type: Journal article
Title: Glutathione-dependent alcohol dehydrogenase AdhC is required for defense against nitrosative stress in Haemophilus influenzae.
Author: Kidd, S.
Jiang, D.
Jennings, M.
McEwan, A.
Citation: Infection and Immunity, 2007; 75(9):4506-4513
Publisher: Amer Soc Microbiology
Issue Date: 2007
ISSN: 0019-9567
Statement of
Kidd, SP; Jiang, D; Jennings, MP. and McEwan, AG.
Abstract: 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.
RMID: 0020092760
DOI: 10.1128/IAI.00487-07
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Appears in Collections:Molecular and Biomedical Science publications

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