Project Details
Projekt
The source of genomic innovation in the human pathogen Acinetobacter baumannii
Applicant
Professor Dr. Ingo Ebersberger
Subject Area
Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
Metabolism, Biochemistry and Genetics of Microorganisms
Metabolism, Biochemistry and Genetics of Microorganisms
Term
from 2014 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 258351992
In the proposed project, we delineate the evolutionary trajectory that has converted Acinetobacter baumannii from a benign environmental bacterium to a life-threatening human pathogen. In a conceptual approach, we investigate how A. baumannii has accomplished the relevant key innovations accounting for this transformation. We focus both on the contribution of horizontal gene transfer, with an emphasis on the direct uptake of environmental DNA, and the modification of genes that pre-existed in the Acinetobacter spp. clade. The complementary, applied part of our proposal aims at elucidating the gene expression program during host infection, providing an alternative path towards understanding A. baumannii virulence. Taken together, our results will contribute to developing an evolutionary systemic view on A. baumannii infection, a necessary prerequisite for controlling this pathogen in the future. We will begin with investigating the general role of horizontal gene transfer for genetic innovation and niche adaptation. Because contaminations in reconstructed genome sequences can severely compromise these analyses, we will establish a minimal information standard for a horizontal gene transfer event. By screening the pan-genome of A. baumannii for horizontally acquired genes, we will then determine the flux of genetic information into and within A. baumannii. In parallel, we model the genomic distribution of horizontally acquired genes under different uptake scenarios. Fitting these models to the observed distributions will help assessing if, and to what extent, the conditional natural competence of many A. baumannii strains allows them to mine their surrounding genetic diversity for genes conveying an adaptive advantage. We will then proceed towards unravelling the mechanistic basis of A. baumannii virulence. On the methods-level, the implementation of protein 3-D structure comparisons into our feature-aware phyletic profiling software, will add another layer of comprehensiveness in assessing the extent of functional diversification between related proteins. We will then screen the A. baumannii pan genome for proteins whose predicted time point of functional diversification can be linked to species- or strain-specific changes in virulence. This comparative genomics-based prediction of virulence factors will be complemented with an in-depth analysis of gene expression in a time course of infection, for both pathogen and a diverse set of hosts systems. This dual-omics approach has three main objectives: It will serve as a scalable first-level evaluation of the in-silico predicted virulence factor candidates. It will help identifying candidates whose contribution to virulence is mediated via an up-regulation of gene expression, or that represent non-coding RNAs. And ultimately, it will reveal the interaction network of A. baumannii genes during infection, together with its plasticity in response to different human tissues, and different host species.
DFG Programme
Research Units
