Life in the cold: how microbes thrive - and die- at extreme temperatures

Deciphering the factors that drive cell death at high temperatures and identifying what enables certain bacteria to endure extreme heat more effectively than others is indeed challenging. The main reason is that temperature impacts virtually all cell components and processes – DNA, protein structure, cell membrane, ... – making it difficult to understand which event or events ultimately lead to cell death.

The cytoplasm of cells is crowded with macromolecules. Among them, proteins are both the most abundant and the more sensitive to temperature. “Protein diffusion through the cytoplasm (proteom dynamics) is critical for cellular metabolism - it plays a fundamental role in cell growth, cell division and in essential biological reactions – and is optimised to maintain functional fluidity at the organism’s working conditions,” explains Beatrice Caviglia (University of Perugia, Italy), the first author of the study now published.

Bacteria Escherichia coli are commonly found in the intestine of humans and other warm-blooded organisms. As temperature raises, protein diffusion undergoes a pronounced slowdown at temperatures near cellular death, coinciding with the early stages of protein unfolding due to temperature. Researchers have recently shown that the unfolding of just a small fraction of the proteins suffices to disrupt diffusion (by creating extended clusters and causing high viscosity) leading to cell death.

“A fundamental question arises: as temperature rises, is the link between protein unfolding, the abrupt slow down of protein diffusion and cell-death a universal phenomenon, also valid for organisms that are adapted to very different thermal niches?” summarises Fabio Sterpone (Université Paris Cité and CNRS).

Interestingly, a striking difference was also observed. For both A. aeolicus and E. coli, the abrupt slowdown on protein diffusion was observed near their respective cell death temperatures. In contrast, for P. arcticus protein diffusion abruptly declines well above the cell death temperature. In other words, when unfolding started and compromised protein diffusion the cell had since long been dead – likely due to the loss of biological activity in key enzymes.

“In P. Arcticus, adapted to very cold conditions, cell-death occurs at a temperature 20 degrees lower than the temperature at which protein unfolding starts. The dynamical arrest and proteome unfolding are thus decoupled from cell metabolic viability,” summarises Alessandro Paciaroni, from the University of Perugia (Italy), one of the main authors of the study.

The results of this study challenges the common view that proteins and the stability and viability of the cell are tightly associated. In the case of P. arcticus, something stops working and the cell dies even without protein unfolding. “These findings redefine the relationship between cytoplasmic dynamics, proteome stability, and bacterial survival,” concludes Paciaroni.

The study provides valuable insights into the thermal vulnerability of different bacterial families, and opens several possible future research directions – what the evolutionary trade-offs for psychrophiles’ heat sensitivity? What caused cell death and can the involved enzymes be stabilised? Such studies are key to informing strategies for food preservation, bioremediation, and the sustainable use of cold-adapted microbes in biotechnology.