Community Research and Development Information Service - CORDIS

FP7

InfeMec Report Summary

Project ID: 631704
Funded under: FP7-PEOPLE
Country: Spain

Periodic Report Summary 1 - INFEMEC (Nanomechanics of proteins involved in viral and bacterial infections)

Viral and bacterial infections are major causes of death worldwide. Infection by viruses such as HIV, and diseases caused by bacteria such as pneumonia, tuberculosis, cholera or miningitis are some of the most prominent infections particularly in the developing world. The HIV/AIDS pandemic affects over 30 million people worldwide. No effective vaccine exist despite tremendous efforts. Similarly, bacterial infections are now a global concern due to the increasing virulence and resistance to antibiotics of many bacterial strains. This is a problem not only affecting the developing world but also the so-called “First World”, where thousands of people die every year due to bacterial infections especially in medical settings . Therefore, it is recognized that viral and bacterial infections are a global problem that requires new research for the development of novel treatments. This new research best involves innovative techniques such as nanotechnology and biotechnology since traditional cell and molecular biology have proven to be insufficient to fully control infections.
Bacteria and viruses infect organisms by using proteins that attach to molecules in the surface of the host. HIV-1 uses its envelope glycoprotein gp120 to attach to CD4 in the surface of T cell. Similarly, the bacterium E. coli uses an array of proteins called pilus for establishing mechanical anchoring to tissues. These proteins withstand mechanical forces that go from few to hundreds of picoNewtons. The effect of these forces in the structure and chemistry of the proteins is not understood but it may have implications in the infection process. In this proposal, we are investigating the role of mechanical forces in the structure and chemistry of the microbial attachment proteins as well as the infection process. We use an array of techniques to study the nanomechanics of viral and bacterial infections progressively from single molecules to cells. We aim to establish new knowledge of the molecular aspects that drive the mechanical interaction of microbes with their targets. First, we use atomic force spectroscopy to explore the effect of mechanical forces in microbial attachment proteins, human CD4 and E. coli pilus. This technique allows monitoring chemical reactions under force such as the reduction of disulfide bonds or the binding of peptides, small molecules and antibodies, processes which are known to be implicated in microbial infections and that may have a mechanical origin. Second, we use bioinformatics to search for molecules that alter the mechanical properties of these anchoring proteins and that can potentially be used to prevent infections. Viral and bacterial infections have been widely studied but there is not much information in the context of mechanical interactions. We believe that our project is providing a new understanding about infectious diseases.
In the past two years we have made substantial progress in all an every one of the objectives of the proposal. We have investigated in depth the mechanical progress of CD4 and bacterial pilus domains FimA, FimF, FimG and FimH. We have investigated the role of disulphide bonds in these moleccules and their role in the mechanics of them. We have also developed novel procedures for searching small molecules that modify their mechanical properties, generating thus potential mechanoactive molecules that could impair the ability the organisms to attach and infect. Overall, we have reach over 50% of our intended results although there is still a lot of work to do to reach a full understanding of force in microbial attachment proteins.

Contact

Miguel Odriozola, (Finance Director)
Tel.: +34 943 57 4000
Fax: +34 943 57 4001
E-mail

Subjects

Life Sciences
Record Number: 196764 / Last updated on: 2017-04-12
Follow us on: RSS Facebook Twitter YouTube Managed by the EU Publications Office Top