PublishedSeptember 7, 2022, 6:11 PM
MedicineEPFL finds a way to fight respiratory infections
By stressing the mitochondria of our cells with an antibiotic, this reduces the damage caused by diseases such as the flu or Covid.
Acute respiratory syndrome can cause death in the elderly or frail.
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Many respiratory infections, such as the flu or Covid-19, inflict significant stress on cells and organs, which can lead to acute respiratory distress syndrome (ARDS), which can lead to death in the elderly or frail.
“New therapeutic approaches aimed at fighting the syndrome instead of fighting the infectious agent might stimulate the host organism’s tolerance” to inflammation by activating its natural responses to stress, explains Professor Johan Auwerx of the Faculty of Life Sciences from EPFL.
A slight stress that outweighs the initial stress
In a recent study published in the «Journal of Clinical Investigation», Adrienne Mottis of EPFL and her colleagues have shown that such an approach can take advantage of a biological phenomenon known as “mitohormesis”. The latter describes the fact that a slight stress undergone by the mitochondria of a cell leads to a series of compensatory phenomena which improve the health and the viability of the cell.
Mitochondria are primarily responsible for a cell’s energy synthesis and are therefore constantly monitored by said cell’s ‘control systems’. If they are malfunctioning or under stress, this continuous quality control can activate compensating responses called “mitochondrial stress responses”.
“A low level of mitochondrial stress can therefore be beneficial for the cell and the organism overall, because the positive effect of these stress responses can outweigh the negative effect of the initial stressor”, explains Adrienne Mottis, who conducted the study. This hypothesis is supported by previous studies revealing that induction of mitohormesis can prolong lifespan by counteracting the effects of age-related or metabolic disorders.
Sensitive to antibiotics
Mitochondria evolved from bacteria in the course of evolution and are therefore also sensitive to certain antibiotics. The researchers therefore examined various antibiotics that might stress the mitochondria. They identified new molecules from the tetracycline family, a class of antibiotics that blocks mitochondrial protein synthesis and is used to fight once morest a number of infections, such as acne, cholera, plague, malaria and syphilis.
Scientists screened 52 tetracyclines and selected molecules, such as 9-tert-butyldoxycycline (9-TB), that are very potent at triggering mitohormesis, even at low doses, while having no antibiotic effect ( i.e. they do not interfere with host bacteria). Following testing in mice, the compounds elicited mild mitochondrial stress and beneficial mitohormetic responses that enhanced the animals’ tolerance to influenza virus infection.
The study reveals that 9-TB induces this tolerance to influenza infection in mice by reducing the extent of inflammatory and tissue damage, without affecting its microbiome. “These results pave the way for new therapies by targeting mitochondria and mitohormesis to combat inflammatory problems and infections,” the authors write.
