Antimicrobial action of 1,10-phenanthroline-based compounds on carbapenemase-producing Acinetobacter baumannii clinical strains: efficacy against planktonic- and biofilm-growing cells

Braz J Microbiol. 2020 Dec;51(4):1703-1710. doi: 10.1007/s42770-020-00351-9. Epub 2020 Jul 31.

Abstract

Therapeutic options are limited for patients infected with Acinetobacter baumannii due to its multidrug-resistance profile. So, the search for new antimicrobials against this gram-negative bacterial pathogen has become a worldwide priority. The present study aimed to evaluate the effects of 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione (phendione), [Ag(phendione)2]ClO4 (Ag-phendione) and [Cu(phendione)3](ClO4)2·4H2O (Cu-phendione) on 26 carbapenemase-producing A. baumannii strains. The susceptibility to carbapenems was performed by detecting the metallo-beta-lactamase (MBL) genes by PCR and by determining the MIC. Also, disk diffusion method was applied to evaluate the susceptibility to other antimicrobial classes. The test compounds were evaluated on both planktonic- and biofilm-growing bacterial cells. The results revealed that all A. baumannii strains had the intrinsic blaoxa-51 gene, and at least one of the blaoxa-23 or blaoxa-24 genes. The geometric mean MIC and minimum bactericidal concentration (MBC) values, respectively, were as follows: Cu-phendione (1.56 and 2.30 μM), Ag-phendione (2.48 and 3.63 μM), phendione (9.44 and 9.70 μM), and phen (70.46 and 184.28 μM). The test compounds (at 0.5 × MIC) affected the biofilm formation and disrupted the mature biofilm, in a typically dose-dependent manner, reducing biomass and viability parameters. Collectively, silver and copper-phendione derivatives presented potent antimicrobial action against planktonic- and biofilm-forming cells of carbapenemase-producing A. baumannii.

Keywords: 1,10-Phenanthroline-5,6-dione; Acinetobacter baumannii; Anti-biofilm action; Antimicrobial activity; Carbapenemase; Metal-based compounds.

MeSH terms

  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / growth & development
  • Acinetobacter baumannii / isolation & purification
  • Acinetobacter baumannii / metabolism
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / metabolism*
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Carbapenems / pharmacology
  • Copper / chemistry
  • Copper / pharmacology
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Phenanthrolines / chemistry
  • Phenanthrolines / pharmacology*
  • Silver / chemistry
  • Silver / pharmacology
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • Phenanthrolines
  • Silver
  • Copper
  • beta-Lactamases
  • carbapenemase
  • 1,10-phenanthroline