Systematic analysis of drug combinations against Gram-positive bacteria.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
23
12
2022
accepted:
30
08
2023
medline:
8
11
2023
pubmed:
29
9
2023
entrez:
28
9
2023
Statut:
ppublish
Résumé
Drug combinations can expand options for antibacterial therapies but have not been systematically tested in Gram-positive species. We profiled ~8,000 combinations of 65 antibacterial drugs against the model species Bacillus subtilis and two prominent pathogens, Staphylococcus aureus and Streptococcus pneumoniae. Thereby, we recapitulated previously known drug interactions, but also identified ten times more novel interactions in the pathogen S. aureus, including 150 synergies. We showed that two synergies were equally effective against multidrug-resistant S. aureus clinical isolates in vitro and in vivo. Interactions were largely species-specific and synergies were distinct from those of Gram-negative species, owing to cell surface and drug uptake differences. We also tested 2,728 combinations of 44 commonly prescribed non-antibiotic drugs with 62 drugs with antibacterial activity against S. aureus and identified numerous antagonisms that might compromise the efficacy of antimicrobial therapies. We identified even more synergies and showed that the anti-aggregant ticagrelor synergized with cationic antibiotics by modifying the surface charge of S. aureus. All data can be browsed in an interactive interface ( https://apps.embl.de/combact/ ).
Identifiants
pubmed: 37770760
doi: 10.1038/s41564-023-01486-9
pii: 10.1038/s41564-023-01486-9
pmc: PMC10627819
doi:
Substances chimiques
Anti-Bacterial Agents
0
Drug Combinations
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2196-2212Subventions
Organisme : European Molecular Biology Laboratory (EMBL Heidelberg)
ID : Internal budget
Organisme : Joint Programming Initiative on Antimicrobial Resistance (Joint Programming Initiative for Antimicrobial Resistance)
ID : Disrupt
Organisme : Joint Programming Initiative on Antimicrobial Resistance (Joint Programming Initiative for Antimicrobial Resistance)
ID : Combinatorials
Informations de copyright
© 2023. The Author(s).
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