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Infect Immun. 2018 Oct 8. pii: IAI.00413-18. doi: 10.1128/IAI.00413-18. [Epub ahead of print]

Acinetobacter baumannii OxyR regulates the transcriptional response to hydrogen peroxide.

Author information

1
Vanderbilt Institute for Infection, Immunology, and Inflammation and Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
2
Department of Chemistry, University of California, Berkeley, CA 94720, USA.
3
Department of Molecular and Cell Biology University of California, Berkeley, CA 94720, USA.
4
Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
5
Vanderbilt Institute for Infection, Immunology, and Inflammation and Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA eric.skaar@vumc.org.

Abstract

Acinetobacter baumannii is a Gram-negative opportunistic pathogen that causes diverse infections, including pneumonia, bacteremia, and wound infections. Due to multiple intrinsic and acquired antimicrobial-resistance mechanisms, A. baumannii isolates are commonly multi-drug resistant and infections are notoriously difficult to treat. The World Health Organization recently highlighted carbapenem-resistant A. baumannii as a 'critical priority' for the development of new antimicrobials because of the risk to human health posed by this organism. Therefore, it is important to discover mechanisms used by A. baumannii to survive stresses encountered during infection in order to identify new drug targets. In this study, we identified hydrogen peroxide (H2O2) as a stressor produced in the lung during A. baumannii infection using in vivo imaging and defined OxyR as a transcriptional regulator of the H2O2 stress response. Upon exposure to H2O2, A. baumannii differentially transcribes several hundred genes. However, transcriptional upregulation of genes predicted to detoxify hydrogen peroxide is abolished in A. baumannii genetically inactivated for the transcriptional regulator oxyR. Moreover, inactivation of oxyR in both antimicrobial-susceptible and multi-drug-resistant A. baumannii strains impairs growth in the presence of H2O2 OxyR is a direct regulator of katE and ahpF1, which encode the major H2O2-degrading enzymes in A. baumannii, as confirmed through measurement of promoter binding by recombinant OxyR in electromobility shift assays. Finally, an oxyR mutant is less fit than wild-type A. baumannii during infection of the murine lung. This work reveals a mechanism used by this important human pathogen to survive H2O2 stress encountered during infection.

PMID:
30297527
DOI:
10.1128/IAI.00413-18

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