Bacterial biofilms raise questions about how life originated

Breaking new ground 25. mar 2021 2 min Senior Research Associate Tomislav Domazet-Lošo Written by Morten Busch

Theories suggest that life originated with a single cell that developed into increasingly more advanced organisms. New analysis of the advanced symbiosis between bacteria in biofilms and the temporal development of their gene and protein expression indicate that biofilm-like structures are a good model of how the original life forms could survive the harsh physical conditions. The researchers behind the study think that the way the bacteria collaborate should provide very different perspectives on how to treat infections in the future.

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Whether life, as theory says, originated from a scorching volcanic source or at one of the ocean's hydrothermal springs, researchers agree that the conditions were harsh. The question is therefore how a single newly formed cell could survive. The researchers behind a new study of biofilms say that it probably did not work that way, and life emerged as symbiosis between several collaborating cells that emerged from a pool of amino acids and genes.

“The cell is undeniably the basic unit of life, but our new studies of biofilms indicate that these bacterial communities behave like multicellular organisms with close communication and collaboration. Further, their development over time can be compared with that of evolution, so old genes are expressed early and biofilms only later express the most recent genes. This information is hugely important in finding the weak points in bacterial biofilms, which are often difficult to combat with antibiotics,” explains Tomislav Domazet-Lošo, Senior Research Associate, Laboratory of Evolutionary Genetics, Division of Molecular Biology, Ruđer Bošković Institute, Zagreb, Croatia.

Younger and older genes

Bacterial biofilms are a major global health concern because of their special ability to tolerate antibiotics. Cells in biofilms have shown up to 1,000 times more antibiotic resistance than single cells, and bacterial biofilms cause 80% of chronic and recurrent microbial infections. This has led to increasing interest in studying these stubborn biofilms and trying to understand how they develop resistance.

“Multicellular behaviour is very common among bacteria, but although it has previously been suggested that they should be considered multicellular organisms, they are most often studied as single organisms and are considered as such. With our new study, we wanted to investigate how these biofilms communicate and develop over time: that is, whether we should consider them as a herd of single cells or one collaborating organism,” says Tomislav Domazet-Lošo.

The researchers therefore thoroughly analysed biofilms of Bacillus subtilis bacteria to determine how the expression of genes and proteins changed through transcriptome and protein profiles. In addition, they used recently developed tools to assess the evolutionary signature of an animal’s development: for example, whether the genes expressed originate from the early or late evolution of the animal.

“We hypothesize that the development of the individual organism – ontogeny – is closely connected with the evolution of the species itself – phylogeny. Our experiments confirmed that the evolutionarily younger and more divergent genes were increasingly expressed later in biofilm growth instead of the old genes,” explains Tomislav Domazet-Lošo.

Understanding bacteria is crucial

The study also showed that the bacteria’s shape, structure and molecular signatures are tightly regulated in well-defined genetic developmental stages – similar to multicellular eukaryotes, for example, as seen in fetal development in humans. The researchers emphasize the similarities between bacterial biofilms and traditional multicellular organisms.

“The way they develop synchronously and differentiate according to where they are in the biofilm is completely reminiscent of what we know from humans and animals – both with stages of development and with the development of various structures in the body according to location, so if we want to become better at understanding the microorganisms, then we must change how we view them ,” says Tomislav Domazet-Lošo.

Tomislav Domazet-Lošo thinks that comparing the bacterial biofilms with multicellular organisms is sufficient. In fact, his theory is that, at the dawn of time, the first life was multicellular organisms. Instead of a single-celled organism emerging in the bacterial primordial soup, he thinks that the first life being multicellular biofilms is far more likely.

“A collaborating multicellular organism had a much greater chance of surviving the violent physiological conditions with high heat and extreme salt and pH conditions. Much evidence suggests that life started multicellularly and that the first single-celled organisms emerged later, only to become multicellular again. At least that is the theory that fits best with the data we have,” explains Tomislav Domazet-Lošo.

This is historically interesting in pure scientific terms, but also viewed with modern glasses, the new knowledge about the evolution, structure and collaboration of biofilms is extremely important.

“Understanding how the bacteria collaborate and are interdependent will make it easier to overcome the great challenges of antibiotic resistance. In this context, examining the developmental stages of biofilms is also important, because there will certainly be some phases in which they are more vulnerable than others,” concludes Tomislav Domazet-Lošo.

Embryo-like features in developing Bacillus subtilis biofilms” has been published in Molecular Biology and Evolution. Several co-authors are employed at the Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby.

LEG embraces three independent research groups that approach questions in evolutionary genetics from different angles.

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