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J. Bacteriol. doi:10.1128/JB.01040-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The OxyR regulon in nontypeable Haemophilus influenzae

Alistair Harrison, William C. Ray, Beth D. Baker, David W. Armbruster, Lauren O. Bakaletz, and Robert S. Munson Jr.*

The Center for Microbial Pathogenesis, Columbus Children's Research Institute, and The Ohio State University College of Medicine and Public Health, 700 Children's Drive, Columbus, OH 43205

* To whom correspondence should be addressed. Email: munsonr{at}ccri.net.


   Abstract

Nontypeable Haemophilus influenzae (NTHi) is a gram negative bacterium and a common commensal of the upper respiratory tract in humans. NTHi causes a number of diseases including otitis media, sinusitis, conjunctivitis, exacerbations of chronic obstructive pulmonary disease and bronchitis. During the course of colonization and infection, NTHi must withstand oxidative stress generated by insult due to multiple reactive oxygen species produced endogenously, by other co-pathogens and by host cells. Using an NTHi-specific microarray, containing oligonucleotides representing the 1821 open reading frames of the recently sequenced NTHi isolate 86-028NP, we have identified 40 genes in strain 86-028NP that are upregulated after induction of oxidative stress due to hydrogen peroxide. Further comparisons between the parent and an isogenic oxyR mutant, identified a subset of 11 genes that were transcriptionally regulated by OxyR, a global regulator of oxidative stress. Interestingly, hydrogen peroxide induced the OxyR-independent upregulation of expression of genes encoding components of multiple iron utilization systems. This finding suggested that careful balancing of levels of intracellular iron was important for minimizing the effects of oxidative stress during NTHi colonization and infection and that there are additional regulatory pathways involved in iron utilization.







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