Portuguese scientists discover potential protection against sepsis in antibiotics

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A team of Portuguese researchers found that a certain group of antibiotics also provides protection against sepsis, in addition to helping with direct infection control, raising the possibility of being used as adjuvant treatments.

In a study published on Wednesday in the medical journal Immunity, the researchers conclude that tetracyclines (broad-spectrum antibiotics) partially inhibit the activity of cellular mitochondria and, in doing so, induce a compensatory response from the body that decreases damage to tissue during an infection, such as sepsis, which results from a generalized infection and is characterized by triggering a deregulated immune response, which causes about 11 million deaths per year worldwide and for which there is no specific treatment.

Why does it happen? According to Luís Moita, a researcher at the Gulbenkian Institute of Science (IGC) who conducted the study, these antibiotics act on a bacterial structure similar to a cellular structure, the mitochondria.

By the way, when they attack bacteria, they also end up acting on the cells, although to a lesser extent, and at that moment they trigger a response that helps “deal with that stress”.

“In a simple way, what happens is that antibiotics have similar targets in the bacteria they intend to kill and in our body and, when they are in our body, they activate responses that help us to deal with the infection”, explained Luís Moita to Lusa.

These responses are triggered by the presence, in most organisms, of defense mechanisms against disorders of homeostasis and one of the main triggers to activate these mechanisms is the activation of alarm signals by the various internal structures of cells, including mitochondria.

In research conducted at IGC, the study authors sought to study a set of drugs known for their ability to interfere with basic cellular functions, to see if there would be other functions in the body that, when disturbed, could lead to compensatory responses that help in responding to infection.

“Based on this idea, we tested drugs and asked ourselves successively what could be protective against sepsis infection and it was in this search that we found this group of antibiotics. From then on, we started to explore the molecular mechanisms that justified their effects ”, described Luís Moita.

In their observations, the researchers found that doxycycline, an antibiotic in the tetracycline family, offers a greater ability to survive sepsis in mice, regardless of its effects on bacterial load.

According to Henrique Colaço, the other author of the study, these benefits extend to the lungs, with reduced cell damage and activation of tissue repair mechanisms.

“In addition, in the liver there is an activation of the stress response and metabolic changes that promote the protection of tissues”, explains the researcher, cited in a note from the IGC.

The team’s next step is a clinical trial, in which tetracyclines will be introduced in the treatment of patients, in order to understand whether they are effectively useful and if they improve the evolution of patients.

For Luís Moita, the conclusions of the study now released open new possibilities for therapy against infections and diseases such as sepsis, based on the increase of mechanisms of tolerance to infection and not only on its control.

“This can open the door to more effective treatment. At this moment, sepsis does not yet have specific therapies and, therefore, everything that arises in this direction will have a very big impact ”, he stresses.



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