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2009/11/5

University of the Basque Country PhD thesis opens way for developing strategies against resistance of bacteria to antibiotics

The Goal of the PhD thesis, undertaken jointly by the Department of Biochemistry and Molecular Biology at the Faculty of Science and Technology of the University of the Basque Country (UPV/EHU) and the Biophysics Unit  (the CSIC-UPV/EHU Mixed Unit) was the protein known as TrwB. This is a coupling protein that enables the interchange of information between bacteria; specifically amongst the conjugative plasmid R388. This protein is found in the internal membrane of bacteria.

In this thesis this protein was isolated and a situation similar to that of TrwB in bacteria was mimicked in liposomes. In this way the characteristics of TrwB could be studied in an environment similar to the natural one and, thus, information obtained about the protein that provided the same about the bacteria. This work, thus, provides important information that enables a better understanding about the mechanism of bacterial conjugation and, as a result, the development of strategies against the spread of resistance to antibiotics in bacteria.

Bacterial conjugation is a (conjugative plasmid) process whereby a bacterium is capable of transmitting a DNA molecule to another by a process which requires physical contact between the two. Thanks to this process, bacteria interchange useful genetic information to deal with their surroundings and adapt to them. Amongst the information shared by the bacteria is that enabling the developing of resistance to various antibiotics. This is why the bacterial conjugation is mainly responsible for disseminating resistance to antibiotics shown by bacteria, a phenomenon which has become a major health problems in recent decades.

In order for this process to take place two groups of proteins have to be codified for the DNA molecule to be transferred. On the one hand, a series of proteins that modify the DNA, so it can be transferred (Dtr proteins) and, on the other, a series of proteins (Mpf proteins) that make up the channel by which the DNA is transferred from the donor bacterium to the receptor one. Both systems are connected by a protein which is indispensable in the bacterial conjugation and known as the “coupling protein”.

Given the modular character of the bacterial conjugation, knowledge about the mechanism of the proteins involved in this process help us to come up with strategies aimed at inhibiting bacterial conjugation, thus enabling the control of information transfer amongst bacteria and, in particular, the dissemination of resistance to antibiotics.

This research has been subsidised with a predoctoral grant from the Basque Government and with projects conceded by the Bizkaia Foru Aldundia (Provincial Government) and the central Ministry of Education and Science.