A Ternary Copper (II) Complex with 4-Fluorophenoxyacetic Acid Hydrazide in Combination with Antibiotics Exhibits Positive Synergistic Effect against Salmonella Typhimurium

Abstract

Salmonella spp. continues to figure prominently in world epidemiological registries as one of the leading causes of bacterial foodborne disease. We characterised 43 Brazilian lineages of Salmonella Typhimurium (ST) strains, characterized drug resistance patterns, tested copper (II) complex as control options, and proposed effective antimicrobial measures. The minimum inhibitory concentration was evaluated for seven antimicrobials, isolated and combined with the copper (II) complex [Cu(4-FH)(phen)(ClO4)2] (4-FH = 4-fluorophenoxyacetic acid hydrazide and phen = 1,10-phenanthroline), known as DRI-12, in planktonic and sessile ST. In parallel, 42 resistance genes were screened (PCR/microarray). All strains were multidrug resistant (MDR). Resistance to carbapenems and polymyxins (86 and 88%, respectively) have drawn attention to the emergence of the problem in Brazil, and resistance is observed also to CIP and CFT (42 and 67%, respectively), the drugs of choice in treatment. Resistance to beta-lactams was associated with the genes blaTEM/blaCTX-M in 39% of the strains. Lower concentrations of DRI-12 (62.7 mg/L, or 100 μM) controlled planktonic and sessile ST in relation to AMP/SUL/TET and AMP/SUL/TET/COL, respectively. The synergistic effect provided by DRI-12 was significant for COL/CFT and COL/AMP in planktonic and sessile ST, respectively, and represents promising alternatives for the control of MDR ST.

Interference with Bacterial Conjugation and Natural Alternatives to Antibiotics: Bridging a Gap

“…In S. Typhimurium, ampicillin resistance rates exceed 75% [17]. In response to this health challenge [18], research is focused on finding actions that reinforce key interventions in combating antibiotic-resistant microorganisms and the mechanisms via which resistance genes are spread [19,20]. In addition, monitoring AMR in E. coli is already a mandatory indicator to verify the occurrence of bacterial phenotypes resistant to clinically important antibiotics such as carbapenems, colistin, and beta-lactams in the environment [21] and in products of animal origin in Europe [21,22].…”

Antimicrobial Resistance Challenged with Platinum(II) and Palladium(II) Complexes Containing 1,10-Phenanthroline and 5-Amino-1,3,4-Thiadiazole-2(3H)-Thione in Campylobacter jejuni

“…In this sense, metal complexes have access to unique modes of action and such mechanisms are difficult if not impossible to replicate with purely organic compounds [ 7 ]. In addition, the use of metal complexes demonstrates therapeutic value and well-documented pharmacological applications [ 8 ] for genera such as Salmonella, among others [ 9 , 10 , 11 , 12 , 13 , 14 ].…”

Editorial for Special Issue “Antibacterial Resistance and Novel Strategies to Eradicate Bacterial Biofilms”

“…The first section exhibits the potential of new antibacterial agents. Monteiro et al (2022) investigated the impact of a laboratory-synthesized copper (II) complex (DRI-12) in combination with different antibiotics against the multi-drug-resistant strains of the food-borne pathogen Salmonella Typhimurium [ 1 ]. Their study showed that Cu(4-FH)(phen)(ClO 4 ) 2 , (a selective copper (II) complex containing 4-fluorophenoxyacetic acid hydrazide and 1,10-phenanthroline) had improved synergism when combined with the antibiotics colistin (COL) and ceftriaxone (CFT), and when combined with COL/Aminopenicillins (AMP) in both the planktonic and the biofilm stages of bacteria.…”

“…Their study showed that Cu(4-FH)(phen)(ClO 4 ) 2 , (a selective copper (II) complex containing 4-fluorophenoxyacetic acid hydrazide and 1,10-phenanthroline) had improved synergism when combined with the antibiotics colistin (COL) and ceftriaxone (CFT), and when combined with COL/Aminopenicillins (AMP) in both the planktonic and the biofilm stages of bacteria. In the absence of DRI-12, different combinations of antibiotics—such as AMP/(sulfonamide) SUL/TET and AMP/ SUL/(tetracycline) TET/COL treatments—showed significantly less impact in comparison with DRI-12/antibiotics combinations [ 1 ].…”