A recent study conducted by a team of international researchers led by the Karolinska Institutet has unveiled critical insights into how tetracycline antibiotics, particularly tigecycline, impair T cell function. These results, published in Nature Communications, provide direct evidence of binding affinity of these antibiotics to mitochondrial ribosomes. This binding prevents oxidative metabolism and promotes immunosuppression.
The key finding of this research is that tetracycline antibiotics are dangerous to both bacterial and human cells. This finding has significant ramifications for our overall understanding of how these antibiotics affect the immune system. It’s this kind of unexpected but exciting new insight that paves the way for breakthroughs in inflammatory disease treatments. It achieves this through the use of reversible inhibition of mitochondrial translation.
Tetracycline Antibiotics and T Cell Function
The spectrum of activity Tetracycline antibiotics have been used for several decades to treat bacterial infections. This new research reveals a concerning side effect: they can impair T cell function. This study makes clear that this class of antibiotics in particular strongly accumulates in mitochondria. Mitochondria are critical organelles that orchestrate energy production and fuelling of metabolism in T cells.
Xaquin Castro Dopico is a research specialist at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. As one of the study’s lead authors, he’s concerned about the bigger picture and that’s the widespread, overuse of antibiotics.
“When you take antibiotics, the effects are not solely restricted to commensal and pathogenic bacteria. Some of your cells take a hit, and there is good evidence in the literature to support reversible inhibition of that mitochondrial translation can be used to treat inflammatory diseases,” – Xaquin Castro Dopico.
This revelation suggests that while tetracycline antibiotics serve a vital role in fighting infections, they may inadvertently compromise the immune system by impairing T cell functionality.
Mechanism of Action: Binding to Mitochondrial Ribosomes
The study goes into exquisite detail of how tigecycline is able to bind to mitochondrial ribosomes and cripple their function. Tetracycline antibiotics profoundly alter the metabolic landscape of T cells. They accomplish this by blocking oxidative phosphorylation (OXPHOS) the main pathway for ATP production. This systemic effect decreases energy availability and directly, beyond cytotoxic activity, suppresses T cell responses.
Dr. Joanna Rorbach, a prominent figure in antibiotic research, notes the importance of this differentiation between bacterial and human mitochondrial ribosomes.
“The discrimination between bacterial and human mitochondrial ribosomes represents an important frontier for antibiotic development. By understanding the specific binding domains within the mitoribosome that interact with tigecycline, it will be possible to design next-generation entities with different specificities, whether those affect the host or pathogen,” – Dr. Joanna Rorbach.
This type of knowledge can be used to design future antibiotics that avoid harming human cells while still targeting and killing pathogens.
Implications for Future Treatments
This study adds to our understanding of mannose in tetracycline antibiotics. Beyond addressing health inequities, it especially opens the door for new therapeutic applications. Similarly, the reversible inhibition of mitochondrial translation presents an exciting new potential strategy of rational design in the treatment of inflammatory disease. By targeting specific mitochondrial functions, researchers are working to create treatments that leverage these effects while preserving immune responses.
The potential implications of this research go much further than immediate clinical application. Scientists are just beginning to understand how antibiotics affect human cells. Their findings may inform novel approaches that minimize the negative impacts of antibiotic treatments.