DksA is a conserved master regulator of stress response in Acinetobacter baumannii

Ram P. Maharjan, Geraldine J. Sullivan, Felise G. Adams, Bhumika S. Shah, Jane Hawkey, Natasha Delgado, Lucie Semenec, Hue Dinh, Liping Li, Francesca L. Short, Julian Parkhill, Ian T. Paulsen, Lars Barquist, Bart A. Eijkelkamp, Amy K. Cain

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
36 Downloads (Pure)

Abstract

Coordination of bacterial stress response mechanisms is critical for long-term survival in harsh environments for successful host infection. The general and specific stress responses of well-studied Gram-negative pathogens like Escherichia coli are controlled by alternative sigma factors, archetypically RpoS. The deadly hospital pathogen Acinetobacter baumannii is notoriously resistant to environmental stresses, yet it lacks RpoS, and the molecular mechanisms driving this incredible stress tolerance remain poorly defined. Here, using functional genomics, we identified the transcriptional regulator DksA as a master regulator for broad stress protection and virulence in A. baumannii. Transcriptomics, phenomics and in vivo animal studies revealed that DksA controls ribosomal protein expression, metabolism, mutation rates, desiccation, antibiotic resistance, and host colonization in a niche-specific manner. Phylogenetically, DksA was highly conserved and well-distributed across Gammaproteobacteria, with 96.6% containing DksA, spanning 88 families. This study lays the groundwork for understanding DksA as a major regulator of general stress response and virulence in this important pathogen.

Original languageEnglish
Pages (from-to)6101-6119
Number of pages19
JournalNucleic Acids Research
Volume51
Issue number12
Early online date9 May 2023
DOIs
Publication statusPublished - 7 Jul 2023

Keywords

  • DksA
  • stress responses
  • Acinetobacter baumannii

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