15 October 2020

New tricks for old antibiotics

Researchers uncovered that a group of antibiotics confers protection against sepsis, beyond their ability to directly control the infection.

Tetracyclines inhibit cell's mitochondria, reducing the damages caused by infections © Joana Carvalho, IGC 2020

The study led by Luís Ferreira Moita, principal investigator at Instituto Gulbenkian de Ciência, and published in the journal Immunity, reveals that tetracyclines (broad spectre antibiotics), by partially inhibiting cell mitochondria activity, induce a compensatory response on the organism that decreases tissue damage caused during infection. This finding opens new doors in the field of disease tolerance and positions this group of antibiotics as potential adjuvant treatment for sepsis, due to their effects that go beyond the control of bacterial burden.

This work highlights the importance of fundamental research and how crucial it is for uncovering new data, which in turn are decisive for the improvement of people’s quality of life. Sepsis is estimated to cause 11 million deaths every year in the world. Its treatment is based on the use of antibiotics and organ support measures, but many times it fails due to unsuccessful attempts at modulating the immune response. Sepsis is a complication that occurs from a generalized infection and is characterized by a dysregulated immune response that entails a high risk of death. Surviving a severe infection requires the activation of mechanisms both of resistance, which reduce the number of infectious agents, and of disease tolerance, which control the damage caused by the immune response and the infectious agents that triggered it. Around one fourth of sepsis patients dies even if the infectious agent is eradicated completely.

Curious about disease tolerance mechanisms and the role of mithochondria on these processes , the researchers selected a group of medical drugs known for their abilities to interfere with basic cell functions. The team observed that doxycycline, an antibiotic belonging to the family of the tetracyclines, confers an increase in mice survival upon sepsis, independently of its effects in the control of bacterial burden. Previous studies performed by others revealed that doxycycline blocks the functioning of a part of cells – the mitochondrial ribosome, which is responsible for protein production in these cellular structures. “We discovered that it is this inhibition of protein production in the mitochondria of the infected organism that explains the observed increase in survival of mice with sepsis, and it is independent of the antibacterial properties of this antibiotic”, explains Luís Ferreira Moita.

For several decades, it has been known that some families of antibiotics provide benefits that go beyond their important antibacterial properties, but so far remain unexplained. “The results we obtained highlight that, in the case of doxycycline, these benefits reach the lungs, where there is a decrease in cell damage and the activation of tissue repair mechanisms. Additionally, in the liver, the stress response is activated together with metabolic changes that promote tissue repair” states Henrique Colaço, also author of the study.

 

Read Press Release

 

Read Paper