Wallenberg Academy Fellows

Unearthing bacterial cell wall diversity in the search for new antibiotics

Felipe Cava’s main goal is to decipher new knowledge on one of the major Achilles heels of bacteria - their cell wall – both to provide answers to scientific fundamental questions and to improve our options to combat pathogenic bacteria.

“We have launched an integrative research program to uncover and exploit the unnoticed variability of the bacterial cell wall through the development of an encyclopedic database. Basically the idea is to gather cell wall chemical and structural signatures in a wide diversity of bacteria and, in addition, uncover how these traits might change in relation with their surrounding environment.”

He hopes that the knowledge gained will result in new antibiotics capable of disarming bacteria instead of killing them.

“It may sound like going against the dogma, but my earlier research at Harvard University suggested to me that bacterial cell walls can be greatly variable and plastic. But it will take a long time and resources to achieve,” Felipe Cava says.

This is why he considers long-term funding of the kind offered to Wallenberg Academy Fellows to be essential.

“Wallenberg Academy Fellows means more than just funding. The accompanying mentorship program helps one to develop as a team leader, which is a good thing and extremely important.”

“Although there is no guarantee of success, we will build a unique platform for a realistic understanding of cell wall biology. The database will be highly relevant to properly understand bacterial relations with neighboring organisms at all levels, and their adaptation to environmental challenges.”

Penicillin revolutionized health care in the 1940s, and has since then saved the lives of millions of people. This antibiotic breaks down the cell walls of bacteria and kills them. The drug is very powerful but a blunt instrument.

“It causes massive bacterial destruction, it attacks most bacterial species and affects the interplay between organisms, including those that are beneficial,” Felipe comments.

Side-effects, such as diarrhea, may then occur. Growing resistance to antibiotics is another reason why new alternatives are urgently needed.

Disarm – not kill

It was long believed that the only good bacterium was one that was dead. But in the last years it has been widely appreciated that we are surrounded by highly diverse and beneficial bacteria.

“The cell walls of bacteria are the epicenter of my research. They serve as a protective barrier but also as a communication interphase with the environment, a kind of window to interpret the surroundings,” Felipe Cava explains.

Felipe is particularly interested in the peptidoglycan layer of cell walls. Many antibiotics prevent peptidoglycan formation, however, relatively little research has been done into finding specific means to target only the cell walls of harmful bacteria.

Today’s knowledge is based on earlier research and just a few bacterial strains produced in unnatural laboratory conditions.

“I want to study the bacteria in their natural environment to see how the cell walls behave in various surroundings, how they are affected by other bacteria, how plastic they can be, and what implications this chemical variability might have for development of pathogenesis and disease.”

Felipe hopes that this research might lead to the development of new species-specific antimicrobials therapies “bacterial slaughter” caused by current antibiotics.

Collaboration essential

Felipe and colleagues discovered certain bacteria secrete substances called non-canonical D-amino acids (NCDAA). NCDAA can destroy or strengthen the cell wall structure of other bacterial strains, a discovery reported in Science 2009.

¬–“There’s an inherent dynamic - not all bacteria produce NCDAA but many of them can still absorb the amino acids and use them. Relationships such as these may prove to be important for our intestinal flora, among other things.”

Study of the cell walls of bacteria is interlinked with many other subject areas, as is evident when Felipe mentions that he is working with some 30 other research teams.

“The field is so complex that broad collaboration is required. In addition, I think it’s a lot of fun.”

Interdisciplinarity is also reflected in his approach to leading his research team at Umeå University.

“My lab is eclectic. I give my colleagues freedom to think, discuss and try out their ideas. Ideas from different people produce a creative environment. I don’t spend much time in the lab myself any longer. I see my science more and more through the eyes of others.”

A good family life essential

Felipe Cava is originally from Spain. He returned to his native country after three years at Harvard. Although he had access to the foremost research programs in Spain, he felt, as a result of the economic crisis, that there was no clear future for him there.

“Funding was spread too thin and was short-term. No-one dared to commit to the unknown. I wanted to break new ground. I had never heard of Umeå, but I was told that several career tracks were available. When I started to learn more about Umeå University I realized that infection biology was a booming research there. All this and the presence of several ‘in-house’ national technical platforms made me realize that this was indeed the place.”

The fact that his wife was also recruited to Umeå University, made his decision even easier.

“Things have to work also for your family. The stamp of quality given by Wallenberg funding is definitely of great help. Quite many people were extremely helpful from the beginning to help us and our two small children to settle in.”

Text Carina Dahlberg
Translation Maxwell Arding
Photo Magnus Bergström