Uridine and pyruvate protect T cells' proliferative capacity from mitochondrial toxic antibiotics: a clinical pilot study

尿苷和丙酮酸保护 T 细胞的增殖能力免受线粒体毒性抗生素的影响:一项临床试验

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作者:Stefano Battaglia #, Stefania De Santis #, Monica Rutigliano, Fabio Sallustio, Angela Picerno, Maria Antonia Frassanito, Ingo Schaefer, Angelo Vacca, Antonio Moschetta, Peter Seibel, Michele Battaglia, Gaetano Villani

Abstract

Antibiotics that inhibit bacterial protein or nucleic acid synthesis and function can exert an off-target action on mitochondria (mitotoxic antibiotics), making actively dividing mammalian cells dependent on uridine and pyruvate supplementation. Based on this rationale, we carried out, for the first time, a randomized pilot study in 55 patients with asymptomatic bacteriuria or positive sperm culture, each treated with a single mitotoxic antibiotic with or without oral supplementation of uridine + pyruvate (Uripyr, Mitobiotix, Italy). The in vivo and ex vivo data show a a 3.4-fold higher value in the differential (before and after the antibiotic treatment) lymphocytes count and a 3.7-fold increase in the percentage of dividing T cells, respectively, in the Uripyr vs the control group. Our findings lay the groundwork to enhance the synergy between antibiotics and the immune system in order to optimize the administration protocols and widen the application potentials of antibiotic therapies as well as to re-evaluate old "forgotten" molecules to fight bacterial infections in the antibiotics resistance era.

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