Fluoroquinolone Metalloantibiotics: A Promising Approach against Methicillin-Resistant Staphylococcus aureus

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Ferreira, M (Author) Other; Bessa, LJ (Author) Other; Sousa, CF (Author) Other; Eaton, P (Author) Other; Bongiorno, D (Author) Other; Stefani, S (Author) Other; Campanile, F (Author) Other; Paula Gameiro (Author) FCUP

Journal

Title: International Journal of Environmental Research and Public Health

Vol. 17 No. 9

Final page: 3127

ISSN: 1661-7827

Publisher: MDPI

Indexing

ISI Web of Knowledge - 9 Citations

Scopus - 9 Citations

Other information

Authenticus ID: P-00S-1NN

DOI: 10.3390/ijerph17093127

Abstract (EN): Fluoroquinolones (FQs) are antibiotics commonly used in clinical practice, although nowadays they are becoming ineffective due to the emergence of several mechanisms of resistance in most bacteria. The complexation of FQs with divalent metal ions and phenanthroline (phen) is a possible approach to circumvent antimicrobial resistance, since it forms very stable complexes known as metalloantibiotics. This work is aimed at determining the antimicrobial activity of metalloantibiotics of Cu(II)FQphen against a panel of multidrug-resistant (MDR) clinical isolates and to clarify their mechanism of action. Minimum inhibitory concentrations (MICs) were determined against MDR isolates of Escherichia coli, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). Metalloantibiotics showed improved antimicrobial activity against several clinical isolates, especially MRSA. Synergistic activity was evaluated in combination with ciprofloxacin and ampicillin by the disk diffusion and checkerboard methods. Synergistic and additive effects were shown against MRSA isolates. The mechanism of action was studied though enzymatic assays and atomic force microscopy (AFM) experiments. The results indicate a similar mechanism of action for FQs and metalloantibiotics. In summary, metalloantibiotics seem to be an effective alternative to pure FQs against MRSA. The results obtained in this work open the way to the screening of metalloantibiotics against other Gram-positive bacteria.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17