Fluoroquinolone Metalloantibiotics: A Promising Approach Against Methicillin-Resistant

Overview

Journal Int J Environ Res Public Health

Publisher MDPI

Specialties Environmental Health
Public Health

Date 2020 May 6

PMID 32365881

Citations 4

Authors

Mariana Ferreira

Lucinda J Bessa

Carla F Sousa

Peter Eaton

Dafne Bongiorno

Stefania Stefani

Floriana Campanile

Paula Gameiro

Affiliations

Soon will be listed here.

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 and methicillin-resistant (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.

Citing Articles

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