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.
Mathers
Jeremy J
JJ
Alpharma, Inc., Animal Health Division, A400 State Street, Chicago Heights, IL 60411, USA.
Clark
Steven R
SR
Hausmann
Denny
D
Tillman
Paul
P
Benning
Valerie R
VR
Gordon
Shelly K
SK
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