Acinetobacter baumannii OxyR Regulates the Transcriptional Response to Hydrogen Peroxide

Lillian J. Juttukonda, Erin R. Green, Zachery R. Lonergan, Marie Heffern, Christopher J. Chang, Eric P. Skaar

Research output: Contribution to journalArticle

13 Scopus citations

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 multidrug 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 the mechanisms used by A. baumannii to survive stresses encountered during infection in order to identify new drug targets. In this study, by use of in vivo imaging, we identified hydrogen peroxide (H2O2) as a stressor produced in the lung during A. baumannii infection and defined OxyR as a transcriptional regulator of the H2O2 stress response. Upon exposure to H2O2, A. baumannii differentially transcribes several hundred genes. However, the transcriptional upregulation of genes predicted to detoxify hydrogen peroxide is abolished in an A. baumannii strain in which the transcriptional regulator oxyR is genetically inactivated. Moreover, inactivation of oxyR in both antimicrobial-susceptible and multidrug-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.

Original languageEnglish (US)
JournalInfection and Immunity
Volume87
Issue number1
DOIs
StatePublished - Jan 1 2019

Keywords

  • Acinetobacter baumannii
  • hydrogen peroxide
  • in vivo imaging
  • OxyR
  • RNA sequencing
  • transcriptional regulation

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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