Unlocking antibiotic resistance with Concepción González-Bello

At the 256th National Meeting and Exposition of the American Chemical Society we spoke to Concepción González-Bello, Professor at the University of Santiago de Compostela, to learn more about her research into novel antibiotic drug targets.

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Concepción González-Bello obtained her PhD at the University of Santiago de Compostela (USC; Spain) in 1994. She joined USC as an Assistant Professor, was promoted to Associate Professor in 2003 and obtained the Spanish habilitation to full Professor in 2011. She joined the Center for Research in Biological Chemistry and Molecular Materials (CiQUS) as a Group Leader in 2011. 

Her main research interest is to develop updated therapies targeting infectious diseases, in particular, drugs with new mechanisms of action. 

Could you please introduce yourself and your institution?

I am an Associate Professor at the University of Santiago de Compostela. I am also a Principal Investigator in a new research center for chemical biology and molecular materials, CiQUS (Santiago de Compostela, Spain). My background is in synthetic organic chemistry; I did my PhD here at the University of Santiago de Compostela on that subject, but then I moved to Cambridge to do my postdoc under the supervision of Professor Abell in chemical biology and enzymology. These are the type of subjects that I am studying now, more in between the chemistry and biology side.

At the ACS Fall Meeting, you presented a talk titled “Disabling unexplored key enzymes in bacteria to unlock resistance to antibiotics.” Can you tell us more about this research?

This was a talk in a symposium focused on antibiotic resistance, and I explained the efforts of my group in trying to find compounds with a new mechanism of action to deal with this big challenge.

Most of the antibiotics that we have – I think – have been working very well, but the problem is that they deal with the same type of targets in the bacteria, and the bacteria have already developed a method to escape. Then, there are a lot of challenges in finding new targets and during the presentation I talked about two potential novel drug targets. In particular, one target related to pathogenesis of the bacteria and another related to metabolism.

These two enzymes are very promising antibiotic drug targets, and there are not yet any compounds on the market to target them.

What are you currently researching?

I am trying to develop new molecules to kill gram-negative bacteria, such as, Pseudomonas aeruginosa, Acinetobacter baumannii and Mycobacterium tuberculosis. These are some of the top threats as identified by the World Health Organization, and what we aim to do is not only discover inhibitors for these targets, but also find out in detail how these target enzymes work. This knowledge can help not only us but also the rest of the scientific community to see if we can go further with these targets because I think that they could be very important.

Our approach is quite multidisciplinary as we have a strong background in synthetic organic chemistry, but also we have been utilizing computational methods, including docking molecular dynamic simulation on the targets.

For some of the targets, there are no crystal structures available so we make the models, but also we model the complex formed between enzymes and ligands – most of the targets are enzymes in our case – and this provides a lot of information on how the enzyme binds with molecules. It is very tough research because you have to be an expert in different parts of the topic, but the information we gain is very detailed.

We also collaborate with microbiologists from the hospital because we are working with bacteria you cannot handle in the lab – they are very, very dangerous pathogens. It is good to have a mix of people from different scientific backgrounds to carry out this research.

Where do you hope the research will head in the future?

Well, we have to do something for the future.

The problem now is that the large pharmaceutical companies are not investing much money on the development of novel antibiotics. There is a lot of effort required to bring a molecule to market and this is not good for them. The reality is that bacteria are very, very smart; bacteria will always develop resistance, but we have to do something to control this because the current levels of bacterial resistance are very high.

I think that we have been doing quite well in the control from the human side, in the administration of antibiotic by the experts, but we still have a long way to come on the veterinary side. We have had many cases of very strong bacteria that have acquired resistance to more than three antibiotics at the same time, and we have to remember that infectious disease is not only a primary infection, but also a threat when you go to hospital to have surgery or you are undergoing another treatment.

It is important to remember about secondary infections, as in the end, unfortunately, many people die not from their initial health concern, but from an infection that they get because their immune system is compromised. I think that even if it is not a very profitable topic for the pharmaceutical industry, we have to do something because we are in the midst of a very large problem. As an academic group, we can help to provide very basic knowledge of these new targets, new compounds and try to keep this resistance against antibiotics under control.

What have you enjoyed most about the ACS National Meeting?

I have never been to such a large conference before! I am really very excited to be here.

There are so many people here so this is the best place to present your work to all of your scientific community, and the meeting is very well organized. The atmosphere has been really nice the whole day and I really look forward to the next one.

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