Identified the cause of the extraordinary resistance of bacterial biofilms

Most living organisms are organized in populations made up of a large number of individuals. This is so even in simple unicellular organisms such as bacteria, which usually coexist in large communities called biofilms.

These communities can be of the order of millions of individuals and coexist in conditions of stress due to the lack of nutrients and the presence of external toxic agents (such as antibiotics and chemical toxins). Despite dealing with such challenging conditions, bacterial biofilms are remarkably resistant and difficult to eradicate.

Resolution of social conflicts in bacterial communities

On July 22, Nature publishes a study coordinated jointly by researchers Jordi García-Ojalvo , from the Department of Experimental and Health Sciences (CEXS) at UPF and Gurol Suel , from the University of California in San Diego (USA). .), which shows how the extraordinary resistance of biofilms is the result of the resolution of a social conflict between bacteria from the interior and the periphery of the bacterial community.

As García-Ojalvo explains , "in situations of nutrient restriction, the bacteria located in the periphery consume most of the available resources and thus greatly limit the nutrients that reach the interior of the biofilm. On the other hand, the interior depends on the periphery to protect themselves from external attacks, as was the case in walled cities in the past, "he commented.

Thus, there is a conflict between the protection of the entire biofilm and the viability of its interior. "Our work shows, through a very close combination of time-lapse microscopy experiments and mathematical models, that the bacterial community resolves this conflict through cyclical stops in biofilm growth," says García-Ojalvo.

A metabolite regulates its growth cycle

These oscillations or cyclical stops in the growth of the biofilm allow the cells of the interior to obtain the nutrients they need, avoiding being drowned by those of the periphery. The viability of the cells of the periphery, at the same time, gives the biofilm a great resistance to external attacks.

To make the biofilm stop its growth periodically, the cells inside produce an essential metabolite that the cells in the periphery depend on in order to proliferate.

Marçal Gabaldà Sagarra , co-author of the work and member of García Ojalvo's team at CEXS-UPF, has been responsible for the development of the mathematical model of the biofilm, and has commented, "We have seen that a metabolic codependency is established that gives rise to a cyclical behavior. When the interior is so stressed that it stops producing metabolite, the cells on the periphery are forced to stop growing. It is then that the nutrients can reach the interior again and the metabolite is produced again, which it allows again the growth of the periphery, thus restarting the cycle ".

A process to eradicate bacterial biofilm

García-Ojalvo has added, "our work also suggests the mechanism to destroy the biofilm." Despite what might be expected, this strategy is based on favoring the continued growth of the periphery that ends up stifling the interior. Once the inside of the biofilm has been destroyed, it is possible to act on the periphery with toxic agents (antibiotics and chemical substances) to eradicate it completely.

The relevance of this study lies in the knowledge it provides to be able to design strategies to counteract bacterial infections in the human body, and also for the disinfection of surfaces affected by biofilms. These results could also help to understand the behavior of other growing cell populations, such as cancerous tumors and embryonic stem cell aggregates.