title: Anti-biofilm activity and synergism of novel thiazole compounds with glycopeptide antibiotics against multidrug-resistant staphylococci.
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) infections are a leading cause of death among all fatalities caused by antibiotic-resistant bacteria. With the rise of increasing resistance to current antibiotics, new antimicrobials and treatment strategies are urgently needed. Thiazole compounds have been shown to possess potent antimicrobial activity. A lead thiazole 1 and a potent derivative 2 were synthesized and their activity in combination with glycopeptide antibiotics was determined against an array of MRSA and vancomycin-resistant S. aureus (VRSA) clinical isolates. In addition, the anti-biofilm activity of the novel thiazoles was investigated against S. epidermidis. Compound 2 behaved synergistically with vancomycin against MRSA and was able to resensitize VRSA to vancomycin, reducing its MIC by 512-fold in two strains. In addition, both thiazole compounds were superior to vancomycin in significantly reducing S. epidermidis biofilm mass. Collectively, the results obtained demonstrate that compounds 1 and 2 possess potent antimicrobial activity alone or in combination with vancomycin against multidrug-resistant staphylococci and show potential for use in disrupting staphylococcal biofilm.
authors.affiliation: Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA.
authors.forename: Haroon
authors.initials: H
authors.lastname: Mohammad
authors.affiliation: Department of Organic Chemistry, Al Azhar University, Cairo, Egypt.
authors.forename: Abdelrahman S
authors.initials: AS
authors.lastname: Mayhoub
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University College of Pharmacy and the Purdue Center for Cancer Research, West Lafayette, IN, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Cushman
authors.affiliation: Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA.
authors.forename: Mohamed N
authors.initials: MN
authors.lastname: Seleem
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D006020:Glycopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013844:Thiazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D014640:Vancomycin / Q000008:administration & dosage / Q000494:pharmacology; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D013844:Thiazoles; D014640:Vancomycin