The cause of the extraordinary resistance of bacterial biofilms has been identified

Most living organisms are organized into populations consisting of a large number of individuals. This is so even in simple single-cell organisms such as bacteria that usually live in large communities called biofilms.

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

Resolution of social conflicts in bacterial communities

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

As García-Ojalvo explains, "in situations of restricted nutrients, bacteria in the peripheral area consume most of the available resources and thereby greatly limit the nutrients that reach the interior of the biofilm. Moreover, the interior depends on the periphery to protect itself from external attacks, in the same way as happened in walled cities in the past".

Thus there is a conflict between protecting the overall population and the viability of the interior. "Our work, through a very close combination of time-lapse microscopy experiments and mathematical models, that the bacterial community resolves this conflict by cyclical stoppages in the growth of the biofilm", says García-Ojalvo.

A metabolite regulates its growth cycle

These cyclical oscillations or stoppages in the growth of the biofilm allow cells inside to get the nutrients they need, avoiding being suffocated by those of the periphery. The viability of the cells in the periphery at the same time provides the biofilm with great resistance to external attacks.

In order for the biofilm to stop its growth periodically, the inner cells produce an essential metabolite on which the peripheral cells depend so that they can proliferate.

Marçal Gabaldà Sagarra, co-author and member of García-Ojalvo's team at the CEXS-UPF, has been responsible for developing the mathematical model of the biofilm and states, "we have seen the establishment of a metabolic codependency that gives rise to cyclical behaviour. When the interior is so stressed that it stops producing metabolite, the cells on the periphery are forced to stop growing. This is when the nutrients can reach the inside again and metabolite is produced once more, again allowing growth of the periphery thus restarting the cycle".

A process to eradicate bacterial biofilm

García-Ojalvo comments "our work also suggests the mechanism to destroy biofilm". Despite what might be expected, this strategy is based on promoting the continued growth of the periphery that ends up stifling the inside. Once the inside of the biofilm has been destroyed, the periphery can be acted upon using toxic agents (antibiotics and chemicals) to fully eradicate it.

The importance of this study lies in the knowledge it contributes to be able to design strategies to counter bacterial infections in the human body, and also to disinfect surfaces affected by biofilms. These results may also help to understand the behaviour of other growing cell populations such as cancerous tumours and embryonic stem cell aggregates.

Reference work: Jintao Liu, Arthur Prindle, Jacqueline Humphries, Marçal Gabalda-Sagarra, Munehiro Asally, Dong-yeon D. Lee, San Ly, Jordi Garcia-Ojalvo, Gürol M. Süel (2015), "Metabolic codependence gives rise to collective oscillations within biofilms", Nature,22 July, DOI: 10.1038/nature14660.