Skip to Main content Skip to Navigation
Journal articles

Species-specific activity of antibacterial drug combinations

Abstract : The spread of antimicrobial resistance has become a serious public health concern, making once treatable diseases deadly again and undermining breakthrough achievements of modern medicine 1,2. Drug combinations can aid in fighting multi-drug resistant (MDR) bacterial infections, yet, are largely unexplored and rarely used in clinics. To identify general principles for antibacterial drug combinations and understand their potential, we profiled ~3,000 dose-resolved combinations of antibiotics, human-targeted drugs and food additives in 6 strains from three Gram-negative pathogens, Escherichia coli, Salmonella Typhimurium and Pseudomonas aeruginosa. Despite their phylogenetic relatedness, more than 70% of the detected drug-drug interactions are species-specific and 20% display strain specificity, revealing a large potential for narrow-spectrum therapies. Overall, antagonisms are more common than synergies and occur almost exclusively between drugs targeting different cellular processes, whereas synergies are more conserved and enriched in drugs targeting the same process. We elucidate mechanisms underlying this dichotomy and further use our resource to dissect the interactions of the food additive, vanillin. Finally, we demonstrate that several synergies are effective against MDR clinical isolates in vitro and during Galleria mellonella infections with one reverting resistance to the last-resort antibiotic, colistin.
Document type :
Journal articles
Complete list of metadatas

Cited literature [43 references]  Display  Hide  Download

https://hal-amu.archives-ouvertes.fr/hal-01915461
Contributor : Delphine Leroi <>
Submitted on : Monday, February 4, 2019 - 4:35:44 PM
Last modification on : Thursday, February 14, 2019 - 11:46:06 AM
Long-term archiving on: : Sunday, May 5, 2019 - 4:22:08 PM

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

Ana Rita Brochado, Anja Telzerow, Jacob Bobonis, Manuel Banzhaf, André Mateus, et al.. Species-specific activity of antibacterial drug combinations. Nature, Nature Publishing Group, 2018, 559 (7713), pp.259 - 263. ⟨10.1038/s41586-018-0278-9⟩. ⟨hal-01915461⟩

Share

Metrics

Record views

252

Files downloads

243