Introduction             

The Intergenomics Group is composed of around 20 researchers with a common general research focus on plasmid biology and, more specifically, the mechanism of bacterial conjugation. Among the members of the group there are experts in microbiology, bacterial genetics, protein engineering, protein purification, crystallography, electron microscopy and biocatalysis. This makes the Intergenomics group a powerful team that can work independently or in cooperation with other research groups.

Bacterial conjugation is the transfer of genetic material between bacteria through direct cell-to-cell contact. Discovered in 1946 by Lederberg and Tatum, conjugation is a mechanism of horizontal gene transfer, as are transformation and transduction, although these mechanisms do not involve cell-to-cell contact.

Bacterial conjugation is a promiscuous DNA transport mechanism. Conjugative plasmids transfer themselves between most bacteria, thus being one of the main causal agents of the spread of antibiotic resistance among pathogenic bacteria.

DNA replication and macromolecule transport across membranes are basic processes of life. If linked, they could form the basis for a new mechanism, DNA secretion, by simply driving the displaced replicating DNA strand to the macromolecular transporter in the membrane. In addition, a new protein is needed to bring the displaced DNA in contact with the transporter: a coupling protein. With this one and only new protein, bacteria could have acquired the basics for conjugation, a mechanism that provides them with a unique means for genetic exchange and a powerful source of genetic variability.

Conjugative DNA-processing enzymes and their substrate DNA sequence (components of the so-called relaxosome) show extended sequence similarity to rolling-circle replication (RCR) systems. Moreover, the set of conjugative proteins that assembles the membrane transporter belong to the type IV secretion system (T4SS) family. A protein acts as a linker between the RCR and the T4SS. It is thus called “coupling protein”, or T4CP, and connects the relaxosome with the membrane transporter.

We use the 34 kb conjugative plasmid R388 as a model, and have analyzed it for nearly two decades. Our interests are, besides the molecular mechanism of conjugation, the study of the regulatory network of R388, the molecular structure of the individual components and their possible uses as biocatalysts of diverse reactions.