Inhibition of Resistance Plasmid Transfer in Escherichia coli by Ionophores, Chlortetracycline, Bacitracin, and Ionophore/Antimicrobial Combinations

Abstract

Medicinal feed additives bacitracin, chlortetracycline (CTC), laidlomycin, lasalocid, and salinomycin inhibited the transfer of multiresistance-conferring plasmid pBR325 (Tet(r) Amp(r) Cp(r), 6.0 kb) into selected gram-negative strains with the use of an in vitro model. High concentrations of ampicillin-sensitive competence-pretreated Escherichia coli HB 101 cells were exposed to 10% (v/v) of 1:10 dimethyl sulfoxide/agent : water containing test mixtures for 0.5 hr prior to plasmid addition and transforming conditions. Transformation was inhibited for all antimicrobials and showed a positive association wich higher concentration. Additional testing of ionophore compounds separately and in combination with bacitracin, chlortetracycline, lincomycin, roxarsone, tylosin, and virginiamycin at representative feed concentrations demonstrated 80.6% to >99.9% inhibition (P < 0.001) of resistance transfer. Bacitracin alone inhibited transformation within the range of 50-500 ppm. No increase in resistance transfer was observed when poultry-derived and reference gram-negative isolates having low or no transformation efficiency were additionally tested. The results suggest that these compounds, at relevant concentrations used in animal feed, may interfere with cell envelope-associated DNA uptake channels or other transformation competence mechanisms. Through these mechanisms, ionophores and cell membrane-interactive feed agents such as CTC and bacitracin may act to inhibit resistance transfer mechanisms within poultry and livestock.

Experiences with drug-free broiler production

“…A Danish study found that 100% of organic broiler flocks, 49.2% of extensive indoor flocks, and 36.7% of conventional flocks were positive for Campylobacter (Heuer et al, 2001). Recent evidence suggests that several ionophores and antibiotics (including chlortetracycline and bacitracin) actually appear to inhibit transfer of genetic elements (specifically the multidrug-resistance plasmid pBR325) among bacteria (including several strains of E. coli and 1 strain of Salmonella typhimurium), possibly reducing the spread of acquired resistance (Mathers et al, 2004).…”

The interface between veterinary and human antibiotic use

“…Antimicrobial agents currently approved for use in animals (bacitracin, chlortetracycline, and ionophores) have been shown to inhibit in vitro resistance plasmid transfer in E. coli. [50][51][52] These studies offer the possibility that new agents used in food animals might themselves contain intrinsic activity to minimize resistance transfer, such as proposed for human pathogens. 53 Novel screening technologies and targets intended for new antimicrobial agents for human therapeutics continue to emerge.…”

Antimicrobial Resistance on Farms: A Review Including Biosecurity and the Potential Role of Disinfectants in Resistance Selection

“…However, the balance of the influences of antimicrobial compounds (in the broadest sense) on the horizontal transfer of AMR on farms is poorly understood, as it may include inhibition as well as promotion of gene transfer. Work on antimicrobials used as growth promoters, plus some (including chlortetracycline and tylosin) used for prophylaxis and therapy, showed considerable inhibition of plasmid transfer into E. coli at normal in‐feed concentrations (Mathers et al., ), while chlorhexidine and some quaternary ammonium compounds (QACs) (applied at or just below their minimum inhibitory concentrations [MICs]) also reduced plasmid transfer (Al‐Masaudi, Day, & Russell, ). Some antibacterial compounds, such as certain unsaturated fatty acids, have a specific antiplasmid‐transfer effect (Getino et al., ).…”