6533b835fe1ef96bd129ec4a

RESEARCH PRODUCT

Molecular topology: A new strategy for antimicrobial resistance control

Maria Galvez-llompartJesús MachucaJorge GalvezJosé-manuel Rodríguez-martínezRamón García-domenechÁLvaro PascualEsther RecachaRiccardo Zanni

subject

0301 basic medicineQuantitative structure–activity relationshipStaphylococcusIn silico030106 microbiologyMicrobial Sensitivity Testsmedicine.disease_causeMicrobiologyStructure-Activity Relationship03 medical and health sciencesAntibiotic resistanceDrug Resistance BacterialDrug DiscoveryEnterococcus faecalisEscherichia colimedicineEscherichia coliPharmacologyVirtual screeningDose-Response Relationship DrugMolecular StructureChemistryOrganic ChemistryBiofilmGeneral MedicineAntimicrobialAnti-Bacterial Agents030104 developmental biologyBiofilmsRegression AnalysisStaphylococcus

description

The control of antimicrobial resistance (AMR) seems to have come to an impasse. The use and abuse of antibacterial drugs has had major consequences on the genetic mutability of both pathogenic and nonpathogenic microorganisms, leading to the development of new highly resistant strains. Because of the complexity of this situation, an in silico strategy based on QSAR molecular topology was devised to identify synthetic molecules as antimicrobial agents not susceptible to one or several mechanisms of resistance such as: biofilms formation (BF), ionophore (IA) activity, epimerase (EI) activity or SOS system (RecA inhibition). After selecting a group of 19 compounds, five of them showed significant antimicrobial activity against several strains of Staphylococcus (2 S. aureus, including 1 methicillin resistant, and 1 S. epidermidis), with MIC values between 16 and 32 mg/L. Among the compounds active on RecA, one showed a marked activity in decreasing RecA gene expression in Escherichia coli.

yearjournalcountryeditionlanguage
2017-03-24European Journal of Medicinal Chemistry
https://doi.org/10.1016/j.ejmech.2017.05.055