|Houlihan, Adam - CORNELL UNIVERSITY|
Submitted to: Antimicrobial Chemotherapy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 2, 2003
Publication Date: November 9, 2003
Citation: Houlihan, A.J., Russell, J.B. 2003. The susceptibility of ionophore-resistant Clostridium aminophilum F to other antibiotics. Journal of Antimicrobial Chemotherapy. 52:623-628. Interpretive Summary: In recent years, there has been a debate concerning the causes of antibiotic resistance, and the European Union has proposed a ban on the routine use of all antibiotics in livestock feed. Beef cattle in feedlots are routinely fed a class of antibiotics known as ionophores, and ionophores increase feed efficiency by as much as 10%. Because ionophores are technically antibiotics, some groups argued that ionophore resistance poses the same public health threat as conventional antibiotics. However, ionophores have never been (nor are likely to be) used as therapy for humans, and they have a distinctly different mode of action. Our research showed that the ruminal bacterium, Clostridium aminophilum F, can be selected to grow with high concentrations of monensin, an ionophore routinely used in beef cattle rations, but adaptation did not cause a significant increase in resistance to other antibiotics. Research on antibiotic has the potential to improve the economics of beef cattle production and human health.
Technical Abstract: Objective: To determine if ionophore-resistant ruminal bacteria are cross-resistant to other classes of antibiotics. Clostridium aminophilum was used as a model organism because this Gram-positive ruminal bacterium can adapt to ionophores (monensin and lasalocid). Non-adapted cultures lagged for at least 12 h with 1 uM monensin or lasalocid and never initiated growth if the concentration was 10 uM. Adapted cultures did not lag with 1 uM monensin or lasalocid, grew well even if the ionophore concentration was 10 uM and had at least 100,000-fold more resistant cells than non-adapted ones. Methods: Ionophore-adapted and non-adapted cultures were assayed for their susceptibility to other classes of antibiotics (penicillin G, ampicillin, cephalosporin C, vancomycin, carbenicillin, tetracycline, chloramphenicol, erythromycin, streptomycin, linocomycin, rifampicin, trimethoprim, novobiocin, polymyxin B and bacitracin) using a broth micro-dilution method. Results: Adapted-cultures retained their resistance phenotype for at least 28 generations even if ionophore was no longer present. Monensin-adapted cultures were as resistant to lasalocid as those adapted to lasalocid, but lasalocid-adapted cultures lagged with 1 uM monensin. Monensin- and lasalocid-resistant C. aminophilum F cultures were as susceptible to most antibiotics as non-adapted cultures. The only antibiotic that seemed to have a common mechanism of resistance was bacitracin, and the ionophore-adapted cultures had a 32-fold greater minimum inhibitory concentration. Conclusion: The use of ionophores in cattle feed and the selection of ionophore-resistant ruminal bacteria does not necessarily lead to other types of antibiotic resistance.