Previous and Current Research

The genus Corynebacterium was originally delineated in 1896 to accommodate bacteria that showed morphological similarities to the diphtheroid bacillus Corynebacterium diphtheriae. Nowadays, it comprises an extremely diverse collection of bacterial species, including the non-pathogenic soil bacterium Corynebacterium glutamicum and many new members isolated from human clinical specimens. Previous and current research projects are focused on the systematic reconstruction of the transcriptional regulatory network (TRN) from C. glutamicum to improve the industrial production of amino acids and on genome sequencing of corynebacteria from the human microflora to deduce the lifestyle of these microorganisms. The complete genome sequence of C. glutamicum ATCC 13032 was established in 2003 at the CeBiTec and had enormous impact on gene expression profiling during the last decade. Rapid advances in associated bioinformatics approaches enabled new strategies for deciphering the architecture of the TRN of C. glutamicum. The TRN is a fundamental biological system controlling the flow of information from the environment toward the gene level and thus to specific cellular functions. It can be conceptualized as the sum total of gene-regulatory interactions in a bacterial cell and reconstructed in form of a directed graph. Our current TRN reconstruction is based on more than 1100 experimentally validated gene-regulatory interactions and revealed a highly connected network that displays a modular and hierarchical structure without feedback regulation at the transcriptional level.

Corynebacteria from the human microflora are increaslingly associated with severe infections in elderly individuals and in immunocompromised patients. Several corynebacteria revealed a remarkable multidrug resistance profile in such a way that only glycopeptide antibiotics remain universally active against these pathogens. The genomes of 27 bacteria from various parts of the phylogenetic tree of the genus Corynebacterium were decoded at the CeBiTec, including the multidrug resistant species Corynebacterium jeikeium and Corynebacterium urealyticum. The genome data revealed that horizontal gene transfer mediated by mobile genetic elements is the main factor contributing to the development of multidrug resistance. Moreover, the interpretation of corynebacterial genome sequences provided comprehensive insights into the gene composition and metabolic capabilities of the respective species and profound information regarding the molecular mechanisms and gene-regulatory networks involved in virulence.

Future Projects and Aims

The skin bacterium Corynebacterium jeikeium is mainly recovered from human axillae and probably plays an important role in human body odor formation due to its lipid-dependent lifestyle. The biotransformation of malodor precursors by lipid-dependent corynebacteria in the human axilla is a well-established route to generate volatile fatty acids that contribute to human body odor. We are currently investigating the molecular basis and the transcriptional regulation of this metabolic route in Corynebacterium jeikeium to understand in more detail the formation of human body odor by corynebacteria and to detect targets for the design of new deodorants.

Comparative genomics approaches and pan-genomics are currently applied to learn more about the production of toxins in Corynebacterium diphtheriae and Corynebacterium pseudotuberculosis strains. In the latter case, the genomic data may help to improve the biotechnological production of phospholipase D that is used as toxoid in vaccination of sheep and goats to effectively control caseous lymphadenitis in these animals. This disease is present in all major sheep and goat production areas of the world and resulted in significant economic losses in wool, milk and meat production.