Inhibition of resistance plasmid transfer in Escherichia coli by ionophores, chlortetracycline, bacitracin, and ionophore/antimicrobial combinations.
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.
Alpharma, Inc., Animal Health Division, A400 State Street, Chicago Heights, IL 60411, USA.
Jeremy J
JJ
Mathers
Steven R
SR
Clark
Denny
D
Hausmann
Paul
P
Tillman
Valerie R
VR
Benning
Shelly K
SK
Gordon
D001414:Bacitracin / Q000494:pharmacology*; D002751:Chlortetracycline / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D007476:Ionophores / Q000494:pharmacology*; D007832:Lasalocid / Q000493:pharmacokinetics / Q000494:pharmacology; D008985:Monensin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010957:Plasmids; D011714:Pyrans / Q000494:pharmacology; D012406:Roxarsone / Q000493:pharmacokinetics; D014169:Transformation, Bacterial / Q000187:drug effects* / Q000235:genetics; D015645:Tylosin / Q000494:pharmacology; D014769:Virginiamycin / Q000494:pharmacology; D000095662:Polyether Polyketides
D001414:Bacitracin; D002751:Chlortetracycline; D007476:Ionophores; D007832:Lasalocid; D008985:Monensin; D011714:Pyrans; D012406:Roxarsone; D015645:Tylosin; D014769:Virginiamycin; C010327:salinomycin; D000095662:Polyether Polyketides; C010208:laidlomycin