Analysts expect to recognize illness resistance instruments in sepsis patients

Analysts expect to recognize illness resistance instruments in sepsis patients


  • Post By : Kumar Jeetendra

  • Source: Gulbenkian Science

  • Date: 16 Oct,2020

Sepsis is estimated to cause 11 million deaths each year in the world. Its treatment is based on the use of antibiotics and organ support measures, but many times it fails because of unsuccessful attempts at controlling the immune reaction.

Surviving a serious infection requires the activation of mechanisms both of resistance.

This 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. Approximately one fourth of tolerance mechanisms expires even if the infectious agent is eradicated entirely.

The team of investigators headed by Luís Ferreira Moita, principal investigator at Instituto Gulbenkian de Ciência (IGC), suggested to identify disease tolerance mechanisms focusing on the role of mitochondria in these processes.

Most organisms have defence mechanisms against homeostasis perturbations (physiological mechanisms that enable organisms to respond to constant internal and environmental changes), which are essential to the initiation of the immune reaction. One of the main triggers relates to the activation of hazard signs once internal structures of the cell begin failing.

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.”-Luís Ferreira Moita, Principal Investigator, Instituto Gulbenkian de Ciência

These structures are essential to the normal functioning of cells and include, amongst others, the mitochondria, known for their essential role in cell metabolism, specifically associated with energy production, which now have roles that extend far beyond that.

The research developed at the IGC selected a group of medical drugs known for their abilities to interfere with fundamental cell functions.

Among these, it was 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 conducted by others demonstrated that doxycycline blocks the performance of a part of cells – the mitochondrial ribosome, which is responsible for protein production in these cellular structures.

For several decades, it’s been known that some families of antibiotics provide benefits that go beyond their antibacterial properties, but so far remain unexplained.

“The results we got highlight that, in the case of doxycycline, these benefits reach the lungs, where there’s a decline in cell damage and the activation of tissue repair mechanisms.

In addition, in the liver, the stress response is activated together with metabolic alterations that promote tissue repair” states Henrique Colaço, also author of the study.

Journal reference:

Colaco, H. G., et al. (2020) Tetracycline Antibiotics Induce Host-Dependent Disease Tolerance to Infection. Immunity.

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