Exploring Copper (II) and Nickel (II) complexes for the control of antimicrobial-resistant Campylobacter jejuni and Escherichia coli

Abstract

Campylobacter jejuni and Escherichia coli are among the main pathogens associated with foodborne diseases, particularly those originating from poultry. The dissemination of multidrug-resistant strains and their ability to form biofilms favor the persistence of these microorganisms in industrial environments and reduce the effectiveness of conventional antimicrobials and sanitizers. In this context, this thesis aimed to evaluate the potential of two copper(II) complexes, [Cu(tta)(bipy)NO₃] and [Cu(tta)(phen)NO₃], and two nickel(II) complexes, [Ni(η²-NO₃)(bta)(phen)] and [Ni(η²-NO₃)(btacl)(phen)], as alternatives for the control of antimicrobial-resistant C. jejuni and E. coli, integrating phenotypic, genomic, and structural approaches. The thesis was organized into three chapters, with Chapter 1 dedicated to the theoretical framework and Chapters 2 and 3 structured as scientific articles. In Chapter 2, four metal complexes were evaluated against five resistant Campylobacter jejuni isolates. All isolates were classified as strong biofilm formers and exhibited a broad genomic repertoire, including 134 virulence genes and multiple determinants associated with resistance to antimicrobials, metals, and biocides. The complexes significantly reduced bacterial viability and biofilm formation, with particular emphasis on the [Ni(η²NO₃)(bta)(phen)] complex, which showed the lowest minimum bactericidal concentration (6.25 µg/mL) and promoted pronounced disruption of the extracellular matrix. Metabolomic analysis identified 408 compounds belonging to 14 chemical classes, revealing alterations consistent with oxidative stress, metabolic imbalance, and impairment of cellular integrity. In Chapter 3, ten Escherichia coli isolates from the poultry production chain were evaluated. Four isolates (40%) were classified as strong biofilm formers, and all exhibited a multidrug-resistant profile, with seven distinct resistance phenotypes. Genomic characterization revealed 28 antimicrobial resistance determinants, 280 virulence genes, 168 genes associated with resistance to metals and biocides, as well as 13 plasmid replicons. The complexes showed bactericidal activity against both planktonic (1.56–100 µg/mL) and sessile cells (25–400 µg/mL), again with superior performance of the [Ni(η²NO₃)(bta)(phen)] complex. Overall, the results demonstrate that metal complexes, particularly nickel(II)-based compounds, have high potential for the control of resistant bacteria associated with biofilms, contributing to the development of innovative strategies within the One Health framework.