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

Mariana Ferreira, Lucinda J. Bessa, Carla F. Sousa, Peter Eaton, Dafne Bongiorno, Stefania Stefani, Floriana Campanile and Paula Gameiro
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Mariana Ferreira: REQUIMTE-LAQV (Rede de Química e Tecnologia – Laboratório Associado para a Química Verde), Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007 Porto, Portugal
Lucinda J. Bessa: REQUIMTE-LAQV (Rede de Química e Tecnologia – Laboratório Associado para a Química Verde), Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007 Porto, Portugal
Carla F. Sousa: REQUIMTE-LAQV (Rede de Química e Tecnologia – Laboratório Associado para a Química Verde), Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007 Porto, Portugal
Peter Eaton: REQUIMTE-LAQV (Rede de Química e Tecnologia – Laboratório Associado para a Química Verde), Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007 Porto, Portugal
Dafne Bongiorno: Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy
Stefania Stefani: Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy
Floriana Campanile: Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy
Paula Gameiro: REQUIMTE-LAQV (Rede de Química e Tecnologia – Laboratório Associado para a Química Verde), Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007 Porto, Portugal

IJERPH, 2020, vol. 17, issue 9, 1-17

Abstract: 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.

Keywords: fluoroquinolones; metalloantibiotics; antimicrobial resistance; methicillin-resistant Staphylococcus aureus; atomic force microscopy (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
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