GSE169081
DksA acts as a transcriptional switch in stress and virulence in Acinetobacter baumannii
Ability to redirect limiting cellular resources accurately is key to bacteria for surviving in harsh environments that they often encounter during their lifetime.  DksA, a transcriptional initiating factor, plays critical roles in regulating stress responses and antibiotic tolerance. Acinetobacter baumannii has become a major healthcare threat and responsible for both nosocomial and community acquired deadly infections worldwide. Yet, little is known about the role of DksA in A. baumannii. Here we describe a highly pleiotropic nature of DksA that it helps redirect the key metabolic pathways associated with the respiration, energy production, protein biosynthesis. Inhibition of ribosomal RNAs, ATP production by DksA is detrimental to bacteria under bacteriostatic stresses such as copper and trimethoprim. By contrast, it is required for survival in stresses that generate reactive-oxygen species such as zinc and gentamycin. Bacteria lacking DksA exhibit increase sensitivity to human serum, promote biofilm formation and capsule production. Not only does DksA show diverse phenotypes in vitro, but it also impacted on virulence in a niche specific manner during in vivo Galleria mellonella and murine infections. Our data collectively provides the detailed insight into the role of DksA in stress protection and virulence in A. baumannii and layout a roadmap for similar findings in other clinically important pathogens. Overall design: Examination of mRNA profiles of A. baumannii wild-type and its dksA knockout mutant under copper or zinc stress stimulations.