Collateral Sensitivity to 4-Hydroxyquinolines in Eimeria acervulina Strains Resistant to Meticlorpindol

Coccidia cultures isolated from 751 commercial broiler houses were tested for sensitivity to buquinolate, decoquinate, and meticlorpindol. Correlations between the anticoccidial indices obtained in these tests revealed an inverse relationship between the responses of these cultures to decoquinate and meticlorpindol. Selection for meticlorpindol resistance in 2 laboratory strains of E. acervulina showed that their 4-hydroxyquinoline sensitivity increased concomitantly with the induction of meticlorpindol resistance. Subsequent selection for decoquinate resistance in these strains was not accompanied by significant increases in meticlorpindol sensitivity. The development of anticoccidial drug resistance is a major obstacle to effective chemotherapeutic control of avian coccidiosis. Periodic rotation of coccidiostats has been practiced as an attempt to cope with this problem. Thus, the possible restoration of drug sensitivity following exposure of resistant strains to other chemically unrelated anticoccidials is an important consideration. Williams (1969) reported the persistence of resistance to meticlorpindol, amprolium, or zoalene among field strains of Eimeria acervulina, E. maxima, and E. tenella following a change of medication to decoquinate. However, McLoughlin (1971) found that the sensitivity of amprolium-, nicarbazin-, or zoaleneresistant strains of E. tenella was restored following 21 generations of exposure to another chemically unrelated coccidiostat. During an investigation of the drug resistance spectra of coccidia cultures isolated from commercial broiler houses, we found evidence of an inverse association between the responses of these strains to decoquinate and to meticlorpindol. Decoquinate (ethyl-6-(decyloxy)-7-ethoxy-4hydroxy-3-quinoline carboxylate) is a 4-hydroxyquinoline coccidiostat which is highly active against several species of Eimeria. All 4hydroxyquinolines possess a similar mode of action by inhibiting the growth of sporozoites once they have reached their usual site of development (Ryley, 1967; Long and Millard, 1968; Challey and Johnson, 1968). Strains of coccidia resistant to any one of the 4-hydroxyquinolines exhibit cross-resistance to all memReceived for publication 26 January 1973. bers of the group (McManus, Campbell, and Cuckler, 1968), suggesting that all of the compounds act upon the same metabolic pathway. Meticlorpindol (3,5-dichloro-2,6-dimethyl4-pyridinol) is similar to the 4-hydroxyquinolines in its anticoccidial effect (Ryley, 1967; Long and Millard, 1968). Coccidia resistant to meticlorpindol exhibit no cross-resistance to other commercially important coccidiostats. Experiments were designed to test the effect of selection for meticlorpindol resistance upon the 4-hydroxyquinoline sensitivity of strains of E. acervulina. The 4-hydroxyquinoline sensitivity of these strains increased concomitantly with the induction of meticlorpindol resistance. A further selection experiment was performed to determine if selection for decoquinate resisance would restore the preexistent meticlorpindol sensitivity of these strains. It is the purpose of this paper to report the results of these studies. MATERIALS AND METHODS Cultures, usually consisting of mixed species of Eimeria, were isolated from 751 commercial broiler houses in which various anticoccidial drugs had been employed. Information on the previous use of 4-hydroxyquinolines and/or meticlorpindol was obtained for 640 of the sites sampled. Additionally, three laboratory-propagated strains of E. acervulina and several substrains derived from them were used in these studies. The 3 parent strains were strain HC and strains F-56-R and F-108-B, 4-hydroxyquinoline-resistant strains which were isolated from broiler flocks under medication with buquinolate and subsequently propagated in a buquinolate environment in the laboratory for 25 and 10 generations, respectively. A compendium of the laboratory strains employed in these studies is shown in Table I.