|Houlihan, Adam - CORNELL UNIVERSITY|
Submitted to: Antimicrobial Chemotherapy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 2, 2003
Publication Date: October 1, 2003
Citation: HOULIHAN, A.J., RUSSELL, J.B. THE SUSCEPTIBILITY OF IONOPHORE-RESISTANT CLOSTRIDIUM AMINOPHILUM F TO OTHER ANTIBIOTICS. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. 2003. V. 52. P. 623-628. Interpretive Summary: In recent years, there has been a debate concerning the causes of antibiotic resistance, and the European Union has propose 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: The ruminal bacterium, Clostridium aminophilum F, was initially sensitive to the ionophores, monensin and lasalocid. Growth was inhibited by 1 =B5M ionophore, but rapid growth was observed after lag times of 12 and 24 h, respectively. The ionophore-treated cultures did not lag a second time and could initiate immediate and rapid growth in 10 =B5M monensin or lasalocid. Treated-cultures had 100,000-fold more resistant cells than non-treated ones, but the resistance phenotype was lost after 28 generations without monensin and 63 generations without lasalocid. We initially thought that ionophore resistance was due to the selection of a sub-population, but subsequent work indicated that virtually any cell could become resistant. This latter observation suggests that ionophore resistance is a physiological adaptation rather than a stable mutation or trait. Monensin-adapted cultures grew rapidly and without lag with 1 =B5M lasalocid, but lasalocid-adapted cultures lagged for 11 h when they were inoculated into 1 =B5M monensin. This means that cross-resistance is possible, but the resistance mechanism is (in at least some cases) ionophore-specific. Ionophore-resistant cultures were as susceptible to penicillin G, ampicillin, cephalosporin C, vancomycin, carbinicillin, tetracycline, chloramphenicol, erythromycin, streptomycin, linocomycin, rifampin, trimethoprim, novobiocin, and polymixin B as ionophore-sensitive ones. The only antibiotic tested that seemed to have a common mechanism of cross-resistance was bacitracin (16-fold increase in MIC). These results are consistent with the idea that ionophore resistance is not necessarily associated with significant cross-resistance to most other classes of antibiotics.