title: The ArcA regulon and oxidative stress resistance in Haemophilus influenzae.
abstract: Haemophilus influenzae transits between niches within the human host that are predicted to differ in oxygen levels. The ArcAB two-component signal transduction system controls gene expression in response to respiratory conditions of growth and has been implicated in bacterial pathogenesis, yet the mechanism is not understood. We undertook a genome-scale study to identify genes of the H. influenzae ArcA regulon. Deletion of arcA resulted in increased anaerobic expression of genes of the respiratory chain and of H. influenzae's partial tricarboxylic acid cycle, and decreased anaerobic expression levels of genes of polyamine metabolism, and iron sequestration. Deletion of arcA also conferred a susceptibility to transient exposure to hydrogen peroxide that was greater following anaerobic growth than after aerobic growth. Array data revealed that the dps gene, not previously assigned to the ArcA modulon in bacteria, exhibited decreased expression in the arcA mutant. Deletion of dps resulted in hydrogen peroxide sensitivity and complementation restored resistance, providing insight into the previously uncharacterized mechanism of arcA-mediated H(2)O(2) resistance. The results indicate a role for H. influenzae arcA and dps in pre-emptive defence against transitions from growth in low oxygen environments to aerobic exposure to hydrogen peroxide, an antibacterial oxidant produced by phagocytes during infection.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Sandy M S
authors.initials: SM
authors.lastname: Wong
authors.forename: Kishore R
authors.initials: KR
authors.lastname: Alugupalli
authors.forename: Sanjay
authors.initials: S
authors.lastname: Ram
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Akerley
mesh_terms: D017353:Gene Deletion; D020869:Gene Expression Profiling; D006193:Haemophilus influenzae / Q000187:drug effects / Q000235:genetics*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009154:Mutation; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000235:genetics*; D010957:Plasmids; D018085:Regulon
chemical_list: D016877:Oxidants; D006861:Hydrogen Peroxide