A team of Portuguese researchers found that a particular 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 cell mitochondria and, in doing so, induce a compensating response from the body that decreases tissue damage during an infection, such as sepsis, which results from a widespread infection and is characterized by triggering an unregulated immune response, which causes around 11 million deaths per year worldwide and for which there is no treatment specific.
Why does this happen? According to Luís Moita, a researcher at the Gulbenkian Institute of Science (IGC) who led the study, these antibiotics act on a bacterial structure similar to a cell structure, the mitochondria.
Due to their similarity, when they attack bacteria they also end up acting on cells, albeit to a lesser extent, and at that time they trigger a response that helps “deal with that stress”.
“In a simple way, what happens is that antibiotics have targets that are similar in the bacteria they intend to kill and in our body, and when they are in our body, they activate responses that help us deal with the infection”, explained Luís Moita to Lusa .
These responses are triggered by the presence, in most organisms, of defense mechanisms against disturbances 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 the research carried out at IGC, the study’s authors sought to study a set of drugs known for their ability to interfere with basic cell functions, to see if there would be other functions in the body that, when disturbed, could lead to compensating responses that help in the response to infection.
“Based on this idea, we tested medications and asked ourselves successively what could be protective against sepsis infection and it was following this search that we found this group of antibiotics. From there we went on to explore the molecular mechanisms that justified its effects” , described Luís Moita.
In their observations, the researchers found that doxycycline, an antibiotic in the tetracycline family, provides an increased 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 a reduction in cell damage and the 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 statement 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 if 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 in mechanisms of tolerance to infection and not only in its control.
“This could open the door to a more effective treatment. At this moment, sepsis still does not have specific therapies and, therefore, anything that arises in this direction will have a very big impact”, he underlines.