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.

Details

Title
Uridine and pyruvate protect T cells’ proliferative capacity from mitochondrial toxic antibiotics: a clinical pilot study
Author
Battaglia Stefano 1 ; De Santis Stefania 2 ; Rutigliano, Monica 3 ; Sallustio Fabio 4 ; Picerno Angela 3 ; Frassanito Maria Antonia 5 ; Schaefer, Ingo 6 ; Vacca, Angelo 5 ; Moschetta, Antonio 4 ; Seibel, Peter 6 ; Battaglia, Michele 3 ; Villani Gaetano 7 

 “Aldo Moro” University of Bari, Department of Interdisciplinary Medicine, Bari, Italy (GRID:grid.7644.1) (ISNI:0000 0001 0120 3326); “Aldo Moro” University of Bari, Department of Emergency and Organ Transplants, Bari, Italy (GRID:grid.7644.1) (ISNI:0000 0001 0120 3326) 
 “Aldo Moro” University of Bari, Department of Interdisciplinary Medicine, Bari, Italy (GRID:grid.7644.1) (ISNI:0000 0001 0120 3326); “Aldo Moro” University of Bari, Department of Pharmacy-Drug Science, Bari, Italy (GRID:grid.7644.1) (ISNI:0000 0001 0120 3326) 
 “Aldo Moro” University of Bari, Department of Emergency and Organ Transplants, Bari, Italy (GRID:grid.7644.1) (ISNI:0000 0001 0120 3326) 
 “Aldo Moro” University of Bari, Department of Interdisciplinary Medicine, Bari, Italy (GRID:grid.7644.1) (ISNI:0000 0001 0120 3326) 
 “Aldo Moro” University of Bari, Department of Biomedical Sciences and Human Oncology, Bari, Italy (GRID:grid.7644.1) (ISNI:0000 0001 0120 3326) 
 University of Leipzig, Molecular Cell Therapy, BBZ, Medical Faculty, Leipzig, Germany (GRID:grid.9647.c) (ISNI:0000 0004 7669 9786) 
 “Aldo Moro” University of Bari, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Bari, Italy (GRID:grid.7644.1) (ISNI:0000 0001 0120 3326) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2542529774
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.