Nanomechanics of pathogenic attachment Uropathogenic Escherichia coli and Human Immunodeciency Virus

Álvaro Alonso, Pre-doctoral Researcher at the nanobiomechanic Group at CIC nanoGUNE, received his PhD at the University of the Basque Country (UPV/EHU) after the defense of his thesis project on 15 December 2017. His research work, entitled “Nanomechanics of pathogenic attachment Uropathogenic Escherichia coli and Human Immunodeciency Virus", has been developed under the supervision of Dr. Raúl Pérez-Jiménez, nanobiomechanic group leader.

The defense consisted of a presentation by the candidate on the main aspects of the Ph.D. thesis project followed by an extended discussion based upon the questions that each one of the members of the committee raised in relation to the research work that has been carried out by Álvaro Alonso during his PhD studies. After its final deliberation, the committee decided to award the candidate the Doctor Degree with the highest mention existing at UPV/EHU (cum laude).

After the defense, we asked Dr. Álvaro Alonso to explain us a bit more about his project:

Which was the subject of your thesis?

Mechanical characterization of proteins involved in the attachment of the pathogens HIV-1 and uropathogenic Escherichia coli to host tissues.

Why did you choose this subject?

Mechanical forces have been demonstrated to be crucial in many biological processes. The pathogenic adhesion to target tissues involves the interaction of both host's and pathogen's surface proteins, and the success of the infection could be directly linked to the ability of these proteins to withstand mechanical stress.

Which metodology/techniques did you use?

Single-molecule force spectroscopy (smFS), Molecular Biology techniques, and Steered Molecular Dynamics simulations.

Which have been the main conclusions?

Proteins used for mechanical attachment to host tissues by uropathogenic E. coli are able to withstand strikingly high forces. This mechanical resistance allows the bacteria to infect and remain attached to the uroepithelium despite of the shear stress induced by the urine flow. In the case of HIV-1, the lymphocyte T cell-surface protein CD4 can be mechanically unfolded at low forces, in the range in which a viral particle could exert. In this low force regime, and with the viral particle attach to it, the CD4 protein could unfold and refold increasing the chances of the virus to interact with other cell-surface proteins required for downstream events leading to infection.

What could be the contribution of your research for present or future nanotechnologies?

Our findings suggest that mechanical forces can play an important role during the pathogenic attachment. The mechanical modulation of proteins involved during the pathogenic attachment could be a potential target for therapeutical intervention and future work should be directed towards this goal.

How do you feel now that you have finished the thesis? Which are your plans for the future?

I have the feeling of having learnt a lot along the way to get my PhD, observing a positive growing trend since I started until I finished. In my immediate future I will keep on doing research as a postdoc, focusing my interests in the characterization and intervention of the mechanical features of proteins used by pathogenic bacteria.

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