Effect of the novel ionophore tetronasin (ICI 139603) on ruminal microorganisms

The antimicrobial activity of the novel ionophore tetronasin (formerly ICI 139603) was compared with that of monensin for the growth of ruminal bacteria, protozoa, and an anaerobic fungus. The potency of tetronasin toward most bacteria and the fungus was an order of magnitude or more greater than that of monensin. Lactobacillus casei was 55 times more sensitive to tetronasin than to monensin, indicating a potential role for tetronasin in reversing lactic acidosis. Bacteria with a gram-positive ultrastructure were generally sensitive to the ionophores and unable to adapt to grow in their presence. The exception was the cellulolytic Ruminococcus flavefaciens, which adapted during successive cultivation on media with increasing ionophore concentrations to grow at 100-fold higher concentrations of tetronasin than were initially lethal to the organism. Gram-negative bacteria were more resistant and generally able to adapt to grow in the presence of both ionophores. An in vivo trial with cattle and in vitro growth experiments indicated that the effect of tetronasin on ciliate protozoa was minor. In vitro experiments measuring hydrogen production by Neocallimastix frontalis suggested that this fungus would be unable to survive in ruminants receiving tetronasin.     

Effect of the novel ionophore tetronasin (ICI 139603) on ruminal microorganisms.

The antimicrobial activity of the novel ionophore tetronasin (formerly ICI 139603) was compared with that of monensin for the growth of ruminal bacteria, protozoa, and an anaerobic fungus. The potency of tetronasin toward most bacteria and the fungus was an order of magnitude or more greater than that of monensin. Lactobacillus casei was 55 times more sensitive to tetronasin than to monensin, indicating a potential role for tetronasin in reversing lactic acidosis. Bacteria with a gram-positive ultrastructure were generally sensitive to the ionophores and unable to adapt to grow in their presence. The exception was the cellulolytic Ruminococcus flavefaciens, which adapted during successive cultivation on media with increasing ionophore concentrations to grow at 100-fold higher concentrations of tetronasin than were initially lethal to the organism. Gram-negative bacteria were more resistant and generally able to adapt to grow in the presence of both ionophores. An in vivo trial with cattle and in vitro growth experiments indicated that the effect of tetronasin on ciliate protozoa was minor. In vitro experiments measuring hydrogen production by Neocallimastix frontalis suggested that this fungus would be unable to survive in ruminants receiving tetronasin.     

Removal of anaerobic fungi from the rumen of sheep by chemical treatment and the effect on feed consumption and in vivo fibre digestion

The population of anaerobic fungi in the rumen of sheep was reduced by the addition of tetronasin (an ionophore antibiotic) to a herbage diet. Fungi were reduced to undetectable levels (< 1 fungal zoospore per ml rumen fluid) by the combined addition of tetronasin and cycloheximide (a protein synthesis inhibitor) and the absence of fungi was maintained with low levels of tetronasin. Sheep with fungi present in the rumen ate 40% more of a straw-based diet (with a fibre digestibility in vivo of 51%) than they ate when without fungi (47% fibre digestibility). Counts of total viable bacteria, cellulolytic bacteria and ciliate protozoa in the rumen were not significantly different when anaerobic fungi were either present or absent.     

Properties of ionophore-resistant Bacteroides ruminicola enriched by cultivation in the presence of tetronasin.

Bacteroides ruminicola M384 was grown in the presence of increasing concentrations of tetronasin, an ionophore that has been developed as a feed additive for ruminants. The resulting culture, B. ruminicola M384/TnR, was then maintained in medium containing 0.1 microgram tetronasin/ml. Growth of the parent strain was eliminated by the addition of 0.1 micrograms tetronasin/ml, but the growth rate of B. ruminicola M384/TnR, which grew more slowly than the parent strain, was unaffected by adding tetronasin. Bacteroides ruminicola M384/TnR retained its resistance to tetronasin even after repeated subculture in the absence of the ionophore, suggesting that a mutation had occurred. The absence of plasmids in individual colonies of B. ruminicola M384/TnR implied that the mutation was chromosomal. Bacteroides ruminicola M384/TnR was also more resistant to the ionophores monensin and lasalocid and, to a lesser degree, to the antibiotic avoparcin than B. ruminicola M384. Binding of [14C]tetronasin to B. ruminicola M384/TnR was lower than binding of the ionophore to the parent stain, and this difference was eliminated by washing cells with EDTA. The peptidolytic activity of B. ruminicola M384 towards triphenylalanine (Mr = 460) was unaffected in B. ruminicola M384/TnR, but the rate of breakdown tetraphenylalanine (Mr = 607) was decreased. This difference was also abolished by EDTA. It was concluded that growth of B. ruminicola in the presence of tetronasin resulted in a mutation affecting the permeability of the cell envelope, such that permeation of tetronasin and molecules of a similar size (Mr = 628) was decreased.     

Properties of ionophore-resistant Bacteroides rurninicola enriched by cultivation in the presence of tetronasin

Bacteroides ruminicola M384 was grown in the presence of increasing concentrations of tetronasin, an ionophore that has been developed as a feed additive for ruminants. The resulting culture, B. ruminicola M384/Tn^R, was then maintained in medium containing 0.1 pg tetronasin/ml. Growth of the parent strain was eliminated by the addition of 0.1 ug tetronasin/ml, but the growth rate of B. ruminicola M384/Tn^R, which grew more slowly than the parent strain, was unaffected by adding tetronasin. Bacteroides ruminicola M384/Tn^R retained its resistance to tetronasin even after repeated subculture in the absence of the ionophore, suggesting that a mutation had occurred. The absence of plasmids in individual colonies of B. ruminicola M384/Tn^R implied that the mutation was chromosomal. Bacteroides ruminicola M384/Tn^R was also more resistant to the ionophores monensin and lasalocid and, to a lesser degree, to the antibiotic avoparcin than B. ruminicola M384. Binding of [¹⁴C]tetronasin to B. ruminicola M384/Tn^R was lower than binding of the ionophore to the parent stain, and this difference was eliminated by washing cells with EDTA. The peptidolytic activity of B. ruminicola M384 towards triphenylalanine ( M _r= 460) was unaffected in B. ruminicola M384/Tn^R, but the rate of breakdown of tetra-phenylalanine ( M _r= 607) was decreased. This difference was also abolished by EDTA. It was concluded that growth of B. ruminicola in the presence of tetronasin resulted in a mutation affecting the permeability of the cell envelope, such that permeation of tetronasin and molecules of a similar size ( M _r= 628) was decreased.     

Enhanced resistance of anaerobic rumen fungi to the ionophores monensin and lasalocid in the presence of methanogenic bacteria

The presence of Methanobrevibacter smithii altered the susceptibility of the anaerobic fungi Neocallimastix frontalis and Piromonas communis to the carboxylic ionophores monensin and lasalocid. The ionophores depressed growth (measured by chitin accretion), the uptake of glucose and the production of H2, formate and acetate by the fungi growing axenically in semi-solid medium. In the presence of M. smithii, the sensitivity of the fungi to monensin and lasalocid was decreased. For example, the uptake of glucose by N. frontalis strain RE1 in the culture was reduced to 50% of the control value by monensin at 0.5 microgram/ml. In the presence of M. smithii strain PS, approximately three times as much monensin was needed to bring about the same effect. In similar tests, the sensitivity of strain RE1 to lasalocid was decreased about nine-fold in the presence of M. smithii. The effect was not observed if the methanogens were killed by autoclaving before inoculation. It is suggested that the enhanced resistance to ionophores in the presence of M. smithii is a consequence of changes in the energy metabolism of the fungi growing in co-culture.     

Effects of some ionophore antibiotics and polyoxins on the growth of anaerobic rumen fungi

The growth of mixed rumen fungi in vitro was suppressed by both ionophore antibiotics (salinomycin, monensin and portmicin) and polyoxins (polyoxin B and D: inhibitors of chitin synthesis). The fungistatic effect of the ionophores on a Piromonas spp. was more pronounced than on a Neocallimastix spp. The polyoxins, however, were more potent fungistatically against the Neocallimastix spp. than the Piromonas spp. Higher concentrations of the polyoxins were required to elicit the same effect as that observed with the ionophores. Salinomycin administration decreased fungal count in the rumen of sheep, but fungal count increased after the cessation of the feeding of the antibiotic. Polyoxin D also suppressed the growth of fungi in vivo, but the effect was short-lived. Nevertheless, both bacterial and protozoal counts tended to increase during and after the administration of polyoxin D. Total volatile fatty acid concentrations in the rumen tended to increase during the period of polyoxin D administration. This increasing tendency was maintained for 10 d after the cessation of antibiotic administration. Offering polyoxin D to sheep increased production of propionate ( P < 0·05), while decreasing that of acetate. The results indicate that the rumen fungi are sensitive to chitin synthesis inhibitors as well as ionophores, and are essential members of microbes in the rumen ecosystem.     

The effect of tetronasin and monensin on fermentation, microbial numbers and the development of ionophore-resistant bacteria in the rumen

The Gram-negative rumen bacteria Fibrobacter succinogenes S85, Prevotella ruminicola M384 and Veillonella parvula L59 were grown in media containing successively increasing concentrations of the ionophores, monensin and tetronasin. All three species became more resistant to the ionophore with which they were grown. Increased resistance to one ionophore caused increased resistance to the other, and cross-resistance to another ionophore—lasalocid—and an antibiotic—avoparcin. Recovery of tetronasin-resistant bacteria from the rumen of monensin-fed sheep increased and vice versa, indicating that similar cross-resistance occurred in vivo.     

Influence of monensin on cation influx and glycolysis of Eimeria tenella sporozoites in vitro

Extracellular Eimeria tenella sporozoites exposed to 1.0 microgram/ml monensin at 40 C had an accelerated rate of sodium influx as well as an increased rubidium uptake that was inhibited by the cardiac glycoside, ouabain. These results suggested the presence of a functional (Na+-K+)-ATPase and its stimulation by monensin. Under the same conditions, sporozoite ATP concentrations declined, lactate production increased and the rate of amylopectin utilization was enhanced. Exposure to monensin also appeared to stimulate the rate of sporozoite glycolysis. The results of this study demonstrated that the cidal effect of monensin on extracellular sporozoites was caused by the capability of the ionophore to act as a transmembrane sodium carrier.     

Enhanced resistance of anaerobic rumen fungi to the ionophores monensin and lasalocid in the presence of methanogenic bacteria

The presence of Methanobrevibacter smithii altered the susceptibility of the anaerobic fungi Neocallimastix frontalis and Piromonas communis to the carboxylic ionophores monensin and lasalocid. The ionophores depressed growth (measured by chitin accretion), the uptake of glucose and the production of H2, formate and acetate by the fungi growing axenically in semi-solid medium. In the presence of M. smithii , the sensitivity of the fungi to monensin and lasalocid was decreased. For example, the uptake of glucose by N. frontalis strain RE1 in the culture was reduced to 50% of the control value by monensin at 0.5 mUg/ml. In the presence of M. smithii strain PS, approximately three tunes as much monensin was needed to bring about the same effect. In similar tests, the sensitivity of strain RE1 to lasalocid was decreased about nine-fold in the presence of M. smithii. The effect was not observed if the methanogens were killed by autoclaving before inoculation. It is suggested that the enhanced resistance to ionophores in the presence of M. smithii is a consequence of changes in the energy metabolism of the fungi growing in co-culture.     

In vitro antifungal activities of anidulafungin and micafungin, licensed agents and the investigational triazole posaconazole as determined by NCCLS methods for 12,052 fungal isolates: review of the literature

The echinocandins anidulafungin and micafungin and the triazole posaconazole are currently undergoing phase III clinical trials. Caspofungin and voriconazole have recently been licensed for the treatment of aspergillosis (both agents), other less common mould (voriconazole) and candidal (caspofungin) infections. This review summarizes the published in vitro data obtained by NCCLS or NCCLS modified methods on the in vitro fungistatic and fungicidal activities of these five agents for yeasts and moulds in comparison to the established agents, amphotericin B, fluconazole, itraconazole, and flucytosine. Among the yeasts, the echinocandins have less activity for Candida parapsilosis and Candida guilliermondii, no activity for Cryptococcus neoformans and Trichosporon spp., but good fungistatic and fungicidal activity in vivo and in vitro for most of the other Candida spp.; this fungicidal activity has been reported by minimum fungicidal concentrations (MFCs) or time kill curve results. The new triazoles exhibit good fungistatic activity (but not fungicidal) for most Candida spp., C. neoformans, and Trichosporon spp. For the Aspergillus spp. evaluated, the echinocandins have similar or better fungistatic activity than those of amphotericin B and the triazoles, but fungicidal activity has been demonstrated only with amphotericin B and the triazoles, with the exception of fluconazole. Most studies showed posaconazole and voriconazole minimum inhibitory concentrations (MICs) ranging from 0.25 to 8 microg/ml for non-solani Fusarium spp., while MIC and minimum effective concentration (MEC) endpoints of the echinocandins were >8 microg/ml. The fungistatic activity of the triazoles is also superior to that of the echinocandins for most of the dimorphic fungi and the Zygomycetes. However, micafungin has activity for the mould phase of most dimorphic fungi, but not for the parasitic or yeast phase of Paracoccidioides brasiliensis. The echinocandins appear to have variable and species dependent fungistatic activity for the dematiaceous fungi, but all agents have poor or no activity against most isolates of Scedosporium prolificans. Only amphotericin B exhibit good fungistatic activity against the Zygomycetes. The combination of caspofungin with some triazoles, amphotericin B or liposomal amphotericin B has been synergistic in vitro, in animal models and in patients. Breakpoints are not available for any mould and antifungal agent combination. In vitro/in vivo correlations should aid in the interpretation of these results, but standard testing conditions are needed for the echinocandins, especially for mould testing, to obtain reliable results.     

Influence of diet and monensin on development of anaerobic fungi in the rumen, duodenum, cecum, and feces of cows

Three cows with fistulated rumens, duodenums, and ceca were fed five different diets: lucerne hay, lucerne hay plus whey (40:60), lucerne hay plus beets (50:50), corn silage plus monensin (40 ppm [40 g/kg] of dry matter intake), and lucerne hay plus monensin (80 ppm of dry matter intake). The fungal population was observed in the rumen, duodenum, cecum, and rectum and varied with diet; it was most abundant with lucerne hay alone and with corn silage plus monensin. The proportion of particles colonized by fungi in the duodenum, the cecum, and feces was measured by microscopic observation and varied from 5 to 50%, depending on the diet. The further sporangia attached to the plant particles were from the rumen, the more likely they were to be devoid of spores. Results confirmed the influence of diet on the development of the ruminal fungal population and showed that monensin does not eliminate these microorganisms. They also confirmed the presence of anaerobic fungi in the ruminant intestine. It is likely that anaerobic fungi leave the rumen attached to plant particles. However, large colonies of nonrhizoidal-type fungi were observed in cecum samples and in feces; at these sites, environmental conditions are perhaps more favorable for this type of fungus than they are in the rumen.     

Influence of diet and monensin on development of anaerobic fungi in the rumen, duodenum, cecum, and feces of cows.

Three cows with fistulated rumens, duodenums, and ceca were fed five different diets: lucerne hay, lucerne hay plus whey (40:60), lucerne hay plus beets (50:50), corn silage plus monensin (40 ppm [40 g/kg] of dry matter intake), and lucerne hay plus monensin (80 ppm of dry matter intake). The fungal population was observed in the rumen, duodenum, cecum, and rectum and varied with diet; it was most abundant with lucerne hay alone and with corn silage plus monensin. The proportion of particles colonized by fungi in the duodenum, the cecum, and feces was measured by microscopic observation and varied from 5 to 50%, depending on the diet. The further sporangia attached to the plant particles were from the rumen, the more likely they were to be devoid of spores. Results confirmed the influence of diet on the development of the ruminal fungal population and showed that monensin does not eliminate these microorganisms. They also confirmed the presence of anaerobic fungi in the ruminant intestine. It is likely that anaerobic fungi leave the rumen attached to plant particles. However, large colonies of nonrhizoidal-type fungi were observed in cecum samples and in feces; at these sites, environmental conditions are perhaps more favorable for this type of fungus than they are in the rumen.     

Effects of the ionophores monensin and tetronasin on simulated development of ruminal lactic acidosis in vitro.

A continuous coculture of four ruminal bacteria, Megasphaera elsdenii, Selenomonas ruminantium, Streptococcus bovis, and Lactobacillus sp. strain LB17, was used to study the effects of the ionophores monensin and tetronasin on the changes in ruminal microbial ecology that occur during the onset of lactic acidosis. In control incubations, the system simulated the development of lactic acidosis in vivo, with an initial overgrowth of S. bovis when an excess of glucose was added to the fermentor. Lactobacillus sp. strain LB17 subsequently became dominant as pH fell and lactate concentration rose. Both ionophores were able to prevent the accumulation of lactic acid and maintain a healthy non-lactate-producing bacterial population when added at the same time as an excess of glucose. Tetronasin was more potent in this respect than monensin. When tetronasin was added to the culture 24 h after glucose, the proliferation of lactobacilli was reversed and a non-lactate-producing bacterial population developed, with an associated drop in lactate concentration in the fermentor. Rises in culture pH and volatile fatty acid concentrations accompanied these changes. Monensin was unable to suppress the growth of lactobacilli; therefore, in contrast to tetronasin, monensin added 24 h after the addition of glucose failed to reverse the acidosis. Numbers of lactobacilli and lactate concentrations remained high, whereas pH and volatile fatty acid concentrations were low.     

Monensin inhibits the secretion of α-amylase but not polysaccharide slime from seedling tissues ofZea mays

Summary The effect of monensin on polysaccharide slime secretion by root tips of corn (Zea mays) was studied. Various treatment times and ionophore concentrations were tested: none resulted in inhibition of slime secretion. Because monensin changes the pH of the medium, its effect was also monitored in strongly buffered media and at different pH's. Even in such media, monensin did not inhibit slime secretion. We also measured the effect of the drug after a pulse with [³H]fucose or a pulse followed by a chase. The amount of labeled slimed secreted was not altered by the ionophore. However, 10M monensin affected the development of root tips and drastically reduced their growth. We showed that monensin inhibits the secretion of -amylase by the scutellum of the same plantlet. The importance of the nature of the secretory compound in relation to monensin inhibition of its secretion is discussed.Abbrevations Hepes N-2-hydroxyethylpiperazine-N-2-ethane-sul-fonic acid - Mes 2-(N-morpholino)ethane-sulfonic acid     

Eimeria tenella: Effect of narasin,a polyether antibiotic on the ultrastructure of intracellular sporozoites

Eimeria tenella sporozoites were inoculated into cultures of chick kidney cells in the presence of 0.01 or 0.1 μg/ml of narasin and incubated at either 40 or 30 C for 24 hr. Electron microscopic examination revealed that either concentration of this polyether ionophore caused extensive ultrastructural damage to the intracellular sporozoite at 40 but not at 30 C, indicating that the severity of the coccidiocidal effect is influenced by temperature. The effect of 0.01 μg/ml monensin on the intracellular parasite was similar to that of narasin, suggesting a common destructive mechanism. The host cells were unaffected by 0.01 μg/ml of narasin at either temperature and by 0.1 μg/ml at 30 C, indicating that the polyether ionophores can be selectively lethal for the parasite. However, when the host cells were treated with 0.1 μg/ml narasin and incubated at 40 C, ultrastructural abnormalities were evident. The results suggest that the coccidiocidal effect of the polyether ionophorous antibiotics may be a general osmotic phenomenon.     

Effects of the ionophores monensin and tetronasin on simulated development of ruminal lactic acidosis in vitro

A continuous coculture of four ruminal bacteria, Megasphaera elsdenii, Selenomonas ruminantium, Streptococcus bovis, and Lactobacillus sp. strain LB17, was used to study the effects of the ionophores monensin and tetronasin on the changes in ruminal microbial ecology that occur during the onset of lactic acidosis. In control incubations, the system simulated the development of lactic acidosis in vivo, with an initial overgrowth of S. bovis when an excess of glucose was added to the fermentor. Lactobacillus sp. strain LB17 subsequently became dominant as pH fell and lactate concentration rose. Both ionophores were able to prevent the accumulation of lactic acid and maintain a healthy non-lactate-producing bacterial population when added at the same time as an excess of glucose. Tetronasin was more potent in this respect than monensin. When tetronasin was added to the culture 24 h after glucose, the proliferation of lactobacilli was reversed and a non-lactate-producing bacterial population developed, with an associated drop in lactate concentration in the fermentor. Rises in culture pH and volatile fatty acid concentrations accompanied these changes. Monensin was unable to suppress the growth of lactobacilli; therefore, in contrast to tetronasin, monensin added 24 h after the addition of glucose failed to reverse the acidosis. Numbers of lactobacilli and lactate concentrations remained high, whereas pH and volatile fatty acid concentrations were low.     

Characterization in vitro and in vivo of resistance to ionophores in a strain of Eimeria tenella.

A field isolate of Eimeria tenella (FS139) was propagated several times in chickens medicated with 200 ppm of dietary monensin. In a laboratory test with 2-wk-old-chickens, the strain was resistant to monensin, salinomycin, and lasalocid given at double use level and was resistant to narasin and maduramicin at the normal use level. In comparison, a laboratory strain (WIS) was controlled by the normal use level of each product. When free WIS sporozoites were treated in vitro with 1.0 microgram/ml of monensin for 0.5 or 4.0 hr at 41 C and inoculated into primary cultures of chicken kidney cells the invasion was reduced by 35.6% or 96.3%, but invasion of FS139 sporozoites was increased by 18.5% by 0.5 hr treatment and was about the same as controls after 2 hr of treatment. Few sporozoites from the WIS strain developed into schizonts, but numerous sporozoites from the FS139 strain developed into normal first and second generation schizonts. The structure of free WIS sporozoites was distorted after 3 hr of treatment with 2.5 micrograms/ml of monensin at 41 C, as observed by light and scanning electron microscopy, whereas there was no change in structure of most treated FS139 sporozoites.     

Localization of the incorporation of 3H-galactose and 3H-sialic acid into thyroglobulin in relation to the block of intracellular transport induced by monensin

Summary The Na⁺/K⁺ ionophore monensin is known to arrest the intracellular transport of newly synthesized proteins in the Golgi complex. In the present investigation the effect of monensin on the secretion of ³H-galactose-labeled and ³H-sialic acid-labeled thyroglobulin was studied in open thyroid follicles isolated from porcine thyroid tissue.Follicles were incubated with ³H-galactose at 20° C for 1 h; at this temperature the labeled thyroglobulin remains in the labeling compartment (Ring et al. 1987a). The follicles were then chased at 37° C for 1 h in the absence or presence of 1 M monensin. Without monensin substantial amounts of labeled thyroglobulin were secreted into the medium, whereas in the presence of the ionophore secretion was inhibited by 80%. Since we have previously shown (Ring et al. 1987 b) that monensin does not inhibit secretion of thyroglobulin present on the distal side of the monensin block we conclude that galactose is incorporated into thyroglobulin on the proximal side of this block.Secretion was also measured in follicles continuously incubated with ³H-galactose for 1 h at 37° C in the absence or presence of monensin. In these experiments secretion of labeled thyroglobulin was inhibited by about 85% in the presence of monensin. Identically designed experiments with ³H-N-acetylmannosamine, a precursor of sialic acid, gave similar results, i.e., almost complete inhibition of secretion of labeled thyroglobulin in the presence of monensin. The agreement between the results of the galactose and sialic acid experiments indicates that sialic acid, like galactose, is incorporated into thyroglobulin on the proximal side of the monensin block.Considering observations made in other cell systems the present results suggest that galactosylation and sialylation of thyroglobulin are completed within the Golgi complex.     

In vitro study of the effect of different ionophore antibiotics and of certain derivatives on rumen fermentation and on protein nitrogen degradation

An in vitro study was carried out to evaluate the effect of different ionophore antibiotics and some of their derivatives on rumen fermentation and on the degradation of peanut meal nitrogen. The increase in the production of propionic acid at the expense of acetic acid, observed with lonomycin, nigericin, cationomycin and lysocellin, was identical to that noted with monensin. The decrease in methanogenesis observed in the presence of monensin was also found with cationomycin and lysocellin. With the exception of lysocellin, which greatly reduced protein degradation of peanut meal, and of nigericin, which had no effect on this parameter, the 2 other molecules presented the same action as monensin. The negative effect of monensin on microbial ammonia uptake was demonstrated with the same intensity in the presence of cationomycin; it was slightly higher with nigericin and particularly accentuated with lonomycin and lysocellin. Three ester derivatives of monensin (monensin acetate, monensin propionate and monensin butyrate) had a similar action to that of monensin on the orientation of rumen fermentations. The monensin isobutyrate derivative appeared to be more active than monensin and only weakly altered microbial ammonia uptake. The oxolonomycin and hydroxolonomycin derivatives behaved identically to lonomycin with respect to microbial metabolism and protein nitrogen degradation. Unlike the molecules from which they derive, the deacylated cationomycin and nigericic acid had no effect on the orientation of rumen fermentations. Of the compounds tested and presenting a potential 'growth-promoting action' at least comparable to that of monensin, and which demonstrated lower toxicity on mice, three molecules (oxolonomycin, lysocellin and cationomycin) appeared to present a zootechnical interest as feed additives for growing cattle.