Project Details
Projekt
Surface-associated motility of Acinetobacter baumannii and its epigenetic control via AamA-specific DNA methylation
Applicant
Privatdozent Dr. Gottfried Wilharm
Subject Area
Metabolism, Biochemistry and Genetics of Microorganisms
Term
from 2014 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 258351992
Surface-associated motility is widespread among clinical isolates of Acinetobacter baumannii and considered to contribute to virulence and persistence in the hospital environment. During the previous funding period we characterized a set of more than 30 motility-deficient mutants with respect to motility, growth, biofilm formation, antibiotic resistance and virulence in the Galleria mellonella infection model. Overall, our studies highlight the interrelatedness of motility, biofilm and virulence properties. Of particular interest, we identified sulfite reductase activity as a crucial factor of biofilm formation, virulence and antibiotic resistance suggesting a role of H2S as a signaling molecule. Moreover, we identified a novel DNA adenine methyltransferase which we functionally characterized and which we termed AamA. For the first time, we investigated the DNA methylome of an A. baumannii strain using single-molecule real time sequencing and our results suggest an AamA-dependent regulon involved in motility and responding to different environmental conditions. Our model is that of an epigenetic control of gene expression via transient DNA methylation mediated by AamA. To scrutinize our hypotheses, we would like to continue to define the AamA-dependent methylome in response to different environmental conditions including motility, biofilm formation, osmotic and antibiotic stress. RT-PCR and RNA sequencing will be applied to define the responses and correlate them with specific methylation patterns. To complement our understanding of the AamA regulon we intend to exploit proteomics approaches to identify AamA interaction partners and to study their influence on DNA methylation. In this way, we expect to contribute to understanding of adaptation processes of this pathogen.
DFG Programme
Research Units
