Evaluation of the best method to assess antibiotic potentiation by phytochemicals against Staphylococcus aureus.
The increasing occurrence of bacterial resistance to antibiotics has now reached a critical level. Finding antibiotic coadjuvants capable to inhibit the bacterial resistance mechanisms would be a valuable mid-term solution, until new classes of antibiotics are discovered. Selected plant alkaloids were combined with 5 antibiotics against 10 Staphylococcus aureus strains, including strains expressing distinct efflux pumps and methicillin-resistant S. aureus strains. The efficacy of each combination was assessed using the microdilution checkerboard, time-kill, Etest, and disc diffusion methods. The cytotoxicity of the alkaloids was evaluated in a mouse fibroblast cell line. Potentiation was obtained in 6% of all 190 combinations, especially with the combination of: ciprofloxacin with reserpine (RES), pyrrolidine (PYR), and quinine (QUIN); tetracycline with RES; and erythromycin with PYR. The highest cytotoxicity values were found for QUIN (half maximal inhibitory concentration [IC50] = 25 ± 2.2 mg/L) and theophylline (IC50 = 100 ± 4.7 mg/L).
LEPABE, Department of Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal.
Ana Cristina
AC
Abreu
Life and Health Sciences Research Institute (ICVS), School of Health Sciences,University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Sofia C
SC
Serra
LEPABE, Department of Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal; CECAV, Centro de Ciência Animal e Veterinária, Departamento de Ciências Veterinárias, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal.
Anabela
A
Borges
CECAV, Centro de Ciência Animal e Veterinária, Departamento de Ciências Veterinárias, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal.
Maria José
MJ
Saavedra
Life and Health Sciences Research Institute (ICVS), School of Health Sciences,University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.
António J
AJ
Salgado
LEPABE, Department of Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal. Electronic address: mvs@fe.up.pt.
Manuel
M
Simões
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D064209:Phytochemicals / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*
D000470:Alkaloids; D000900:Anti-Bacterial Agents; D064209:Phytochemicals
Alkaloids; Co-therapy; Efflux pump; Potentiation; Resistance-modifying agents