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PloS One 2013Surviving predation is a fitness trait of Escherichia coli O157:H7 (EcO157) that provides ample time for the pathogen to be transported from reservoirs (e.g. dairies and...
Surviving predation is a fitness trait of Escherichia coli O157:H7 (EcO157) that provides ample time for the pathogen to be transported from reservoirs (e.g. dairies and feedlots) to farm produce grown in proximity. Ionophore dietary supplements that inhibit rumen protozoa may provide such a selective advantage for EcO157 to proliferate in lagoons as the pathogen is released along with the undigested supplement as manure washings. This study evaluated the fate of an outbreak strain of EcO157, protozoan and bacterial communities in wastewater treated with monensin. Although total protozoa and native bacteria were unaffected by monensin, the time for 90% decrease in EcO157 increased from 0.8 to 5.1 days. 18S and 16S rRNA gene sequencing of wastewater samples revealed that monensin eliminated almost all colpodean and oligohymenophorean ciliates, probably facilitating the extended survival of EcO157. Total protozoan numbers remained high in treated wastewater as monensin enriched 94% of protozoan sequences undetected with untreated wastewater. Monensin stimulated 30-fold increases in Cyrtohymena citrina, a spirotrichean ciliate, and also biflagellate bicosoecids and cercozoans. Sequences of gram-negative Proteobacteria increased from 1% to 46% with monensin, but gram-positive Firmicutes decreased from 93% to 46%. It is noteworthy that EcO157 numbers increased significantly (P<0.01) in Sonneborn medium containing monensin, probably due to monensin-inhibited growth of Vorticella microstoma (P<0.05), a ciliate isolated from wastewater. We conclude that dietary monensin inhibits ciliate protozoa that feed on EcO157. Feed supplements or other methods that enrich these protozoa in cattle manure could be a novel strategy to control the environmental dissemination of EcO157 from dairies to produce production environments.
Topics: Animals; Cattle; Dairying; Disease Outbreaks; Escherichia coli O157; Ionophores; Monensin; RNA, Ribosomal, 16S; RNA, Ribosomal, 18S; Rumen; Wastewater
PubMed: 23349969
DOI: 10.1371/journal.pone.0054782 -
Journal of Dairy Science Feb 2014The objective of this study was to determine the effects of monensin (M) supplementation on lactation performance of dairy cows fed diets of either reduced (RS) or... (Randomized Controlled Trial)
Randomized Controlled Trial
The objective of this study was to determine the effects of monensin (M) supplementation on lactation performance of dairy cows fed diets of either reduced (RS) or normal (NS) starch concentrations as total mixed rations. One hundred twenty-eight Holstein and Holstein × Jersey cows (90 ± 33 d in milk) were stratified by breed and parity and randomly assigned to 16 pens of 8 cows each in a randomized controlled trial. Pens were then randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement of treatments. A 4-wk covariate adjustment period preceded the treatment period, with all pens receiving NS supplemented with 18 g of monensin/t of dry matter (DM). Following the 4-wk covariate adjustment period, cows were fed their assigned treatment diets of NS with M (18 g of monensin/t), NS with 0 g of monensin/t (C), RS with M, or RS with C for 12 wk. Actual starch concentrations for the RS and NS diets were 20.4 and 26.9% (DM basis), respectively. Mean dry matter intake (DMI; 27.0 kg/d) was unaffected by the treatments. Feeding M compared with C and NS compared with RS increased milk yield by 1.3 and 1.5 kg/d per cow, respectively. Milk protein percentage and yield and lactose yield were increased and milk urea nitrogen was decreased for NS compared with RS. Feeding M increased actual and component-corrected milk feed efficiencies (component-corrected milk yield/DMI) and lactose yield and tended to increase milk urea nitrogen compared with C. Milk protein percentage was decreased for M compared with C, but milk fat percentage and yield, protein yield, and lactose percentage were unaffected by M. We observed a tendency for a starch × monensin interaction for milk feed efficiency (actual milk yield/DMI); M tended to increase efficiency more for NS than for RS. Starch and monensin had minimal effects on milk fatty acid composition and yields. Feeding RS decreased milk and protein yields, but component-corrected milk yields and feed efficiencies were similar for RS and NS. Monensin increased feed efficiency and lactation performance for both dietary starch concentrations.
Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Cattle; Diet; Dietary Carbohydrates; Dietary Supplements; Fatty Acids; Female; Lactation; Milk Proteins; Monensin; Pregnancy; Proton Ionophores; Starch
PubMed: 24342685
DOI: 10.3168/jds.2013-6756 -
Antimicrobial Agents and Chemotherapy Sep 2015The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual...
The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual stages of Plasmodium, thus with both curative and transmission-blocking activities. The aim of the present work was to investigate whether the class of monovalent ionophores, which includes drugs used in veterinary medicine and that were recently proposed as human anticancer agents, meets these requirements. The activity of salinomycin, monensin, and nigericin on Plasmodium falciparum asexual and sexual erythrocytic stages and on the development of the Plasmodium berghei and P. falciparum mosquito stages is reported here. Gametocytogenesis of the P. falciparum strain 3D7 was induced in vitro, and gametocytes at stage II and III or stage IV and V of development were treated for different lengths of time with the ionophores and their viability measured with the parasite lactate dehydrogenase (pLDH) assay. The monovalent ionophores efficiently killed both asexual parasites and gametocytes with a nanomolar 50% inhibitory concentration (IC50). Salinomycin showed a fast speed of kill compared to that of standard drugs, and the potency was higher on stage IV and V than on stage II and III gametocytes. The ionophores inhibited ookinete development and subsequent oocyst formation in the mosquito midgut, confirming their transmission-blocking activity. Potential toxicity due to hemolysis was excluded, since only infected and not normal erythrocytes were damaged by ionophores. Our data strongly support the downstream exploration of monovalent ionophores for repositioning as new antimalarial and transmission-blocking leads.
Topics: Antimalarials; Cell Line; Erythrocytes; Hemolysis; Humans; Inhibitory Concentration 50; Ionophores; Molecular Structure; Monensin; Nigericin; Plasmodium berghei; Plasmodium falciparum; Pyrans
PubMed: 26055362
DOI: 10.1128/AAC.04332-14 -
Journal of Dairy Science Oct 1989Effects of isoacids, monensin, or a combination of them on fermentation by mixed rumen bacteria were investigated using a continuous culture technique. The culture was...
Effects of isoacids, monensin, or a combination of them on fermentation by mixed rumen bacteria were investigated using a continuous culture technique. The culture was allowed to stabilize for 4 d before treatments were imposed. Comparisons between treatments were made on d 11 and 12 of the culture. Isoacids (equal proportions of isobutyric, 2-M-butyric, isovaleric, and valeric acids) at 15 mg/dl of culture media increased acetate (6.17 vs. 5.48 meq/dl) and total VFA production (8.93 vs. 7.87 meq/dl) compared with that of controls. Monensin at 150 micrograms/dl reduced acetate (3.74 vs. 6.02 meq/dl) and VFA (6.84 vs. 8.54 meq/dl) but increased propionate (2.28 vs. 1.74 meq/dl) relative to control. The combination of isoacids and monensin increased acetate relative to monensin alone (5.24 vs. 3.74 meq/dl) but did not alter the effect of monensin on propionate concentration (2.32 vs. 2.28 meq/dl). It is concluded that monensin decreases acetate production by 35% and when isoacids are added to the cultures containing monensin, acetate production is restored.
Topics: Animals; Butyrates; Butyric Acid; Cattle; Fatty Acids, Volatile; Female; Fermentation; Hemiterpenes; Isobutyrates; Monensin; Pentanoic Acids; Rumen
PubMed: 2600235
DOI: 10.3168/jds.S0022-0302(89)79420-0 -
Poultry Science Sep 1990Two series of experiments were conducted to assess the relative ability of strains of Eimeria acervulina and Eimeria tenella to develop resistance to monensin (MON),...
Two series of experiments were conducted to assess the relative ability of strains of Eimeria acervulina and Eimeria tenella to develop resistance to monensin (MON), nicarbazin (NIC), and the monensin plus nicarbazin combination (MON plus NIC). The studies were designed so that drug concentrations in the selection experiments were increased whenever possible. During selection, E. acervulina increased its reproductive index in the presence of NIC or MON plus NIC, equivalent selection in the presence of MON resulted in only a slight increase in reproductive ability. Eimeria tenella, however, was unable to increase its reproductive capacity to the respective drugs. Sensitivity tests after 60 generations of selection revealed that patterns of resistance development for E. acervulina and E. tenella corresponded with the changes in reproductive indices established in the selection experiments. Thus, results of these tests indicate that E. acervulina possesses the ability to develop resistance to NIC and MON plus NIC. Under essentially the same conditions of selection, E. tenella developed only partial resistance to the respective drugs.
Topics: Animals; Chickens; Coccidiosis; Drug Combinations; Drug Resistance; Eimeria; Male; Monensin; Nicarbazin; Poultry Diseases
PubMed: 2247409
DOI: 10.3382/ps.0691485 -
Poultry Science Dec 1986Effects of the ionophoric anticoccidial agent monensin on glucose and amino acid absorption were investigated in young broiler chickens. Chicks housed in cages with wire...
Effects of the ionophoric anticoccidial agent monensin on glucose and amino acid absorption were investigated in young broiler chickens. Chicks housed in cages with wire floors were fed a practical diet containing 0 or 121 ppm monensin for 2 to 3 weeks prior to measurement of nutrient absorption. Chicks were anesthetized with halothane, and the intestine was accessed through an incision in the abdominal wall. A 10-cm segment of the intestine immediately anterior to Meckel's diverticulum was rinsed free of digesta and used for measurement of absorption in situ. One milliliter of saline solution containing 2 mM of glucose or a mixture of amino acids was injected into the lumen of the ligated segment, and recovery of glucose and amino acids in the lumen was determined after 4- and 5-min intervals, respectively. In one glucose study, the solution contained 0, 1, 10, or 80 micrograms/ml of monensin. In one amino acid study, the solution contained 0, 5, or 80 micrograms/ml of monensin; in subsequent studies, monensin was not included in the solution. Results show that neither dietary monensin nor monensin in the saline solution affected glucose absorption. Dietary monensin tended to depress lysine absorption but increased the absorption of tryptophan and arginine, the latter amino acid being markedly affected by monensin. Dietary monensin alone had no effect on absorption of cystine, isoleucine, methionine, or threonine. Inclusion of monensin in the saline solution depressed methionine absorption but only when birds also had been fed the diet containing monensin. Monensin in the saline solution depressed isoleucine absorption irrespective of dietary treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Amino Acids; Animals; Chickens; Glucose; Intestinal Absorption; Monensin
PubMed: 3575218
DOI: 10.3382/ps.0652292 -
Journal of Virology Jan 2019The alphaherpesvirus pseudorabies virus (PRV) is the causative agent of pseudorabies, a disease of great economic and welfare importance in swine. Other...
The alphaherpesvirus pseudorabies virus (PRV) is the causative agent of pseudorabies, a disease of great economic and welfare importance in swine. Other alphaherpesviruses, including herpes simplex virus (HSV), utilize low-pH-mediated endocytosis to enter a subset of cell types. We investigated whether PRV used this entry pathway in multiple laboratory model cell lines. Inhibition of receptor-mediated endocytosis by treatment with hypertonic medium prevented PRV entry. PRV entry into several cell lines, including porcine kidney (PK15) cells and African green monkey kidney (Vero) cells, was inhibited by noncytotoxic concentrations of the lysosomotropic agents ammonium chloride and monensin, which block the acidification of endosomes. Inactivation of virions by acid pretreatment is a hallmark of viruses that utilize a low-pH-mediated entry pathway. Exposure of PRV virions to pH 5.0 in the absence of host cell membranes reduced entry into PK15 and Vero cells by >80%. Together, these findings suggest that endocytosis followed by fusion with host membranes triggered by low endosomal pH is an important route of entry for PRV. PRV is a pathogen of great economic and animal welfare importance in many parts of the world. PRV causes neurological, respiratory, and reproductive disorders, often resulting in mortality of young and immunocompromised animals. Mortality, decreased production, and trade restrictions result in significant financial losses for the agricultural industry. Understanding the molecular mechanisms utilized by PRV to enter host cells is an important step in identifying novel strategies to prevent infection and spread. A thorough understanding of these mechanisms will contribute to a broader understanding of alphaherpesvirus entry. Here, we demonstrate PRV entry into multiple model cell lines via a low-pH endocytosis pathway. Together, these results provide a framework for elucidating the early events of the PRV replicative cycle.
Topics: Ammonium Chloride; Animals; Cell Line; Cell Membrane; Chlorocebus aethiops; Endocytosis; Herpesvirus 1, Suid; Hydrogen-Ion Concentration; Monensin; Swine; Vero Cells; Virus Internalization
PubMed: 30355685
DOI: 10.1128/JVI.01849-18 -
Journal of Dairy Science Jul 2009Two experiments (Exp. 1 and 2) were conducted using a 4 x 4 Latin square design with 2 replications (n = 8) to evaluate effects of feeding Holstein dairy cows a total...
Effects of dietary forage level and monensin on lactation performance, digestibility and fecal excretion of nutrients, and efficiency of feed nitrogen utilization of Holstein dairy cows.
Two experiments (Exp. 1 and 2) were conducted using a 4 x 4 Latin square design with 2 replications (n = 8) to evaluate effects of feeding Holstein dairy cows a total mixed ration containing 50 or 60% of ration dry matter (DM) from forages with or without supplementation of monensin. In Exp. 1, alfalfa silage (AS) was used as the major forage (55% forage DM), and corn silage (CS; 45% forage DM) was used to make up the rest of the forage portion of diets (55AS:45CS). In Exp. 2, CS was used as the major forage (70% forage DM) and alfalfa hay (AH; 30% forage DM) was used to make up the rest of the forage portion of diets (70CS:30AH). Experimental diets were arranged in a 2 x 2 factorial with 50 or 60% ration DM from forages and monensin supplemented at 0 or 300 mg/cow daily. In Exp. 1 (55AS:45CS), feeding 60% forage diets decreased DM intake (DMI; 27.3 vs. 29.6 kg/d) but maintained the same levels of milk (45.8 vs. 47.0 kg/d) compared with 50% forage diets. The efficiency of converting feed to milk or 3.5% fat-corrected milk was greater for cows fed 60% compared with 50% forage diets (1.7 vs. 1.6 kg milk or 3.5% fat-corrected milk/kg of DMI, respectively). Increasing dietary forage level from 50 to 60% of ration DM increased milk fat percentage (3.4 to 3.5%); however, adding monensin to the 60% forage diet inhibited the increase in milk fat percentage. Feeding 60% forage diets decreased feed cost, but this decrease ($0.5/head per day) in feed cost did not affect income over feed cost. Feeding 60% forage diets decreased fecal excretion of DM (10.6 to 9.6 kg/d) and nitrogen (N; 354 to 324 g/d) and improved apparent digestibility of neutral detergent fiber from 43 to 49% and apparent efficiency of feed N utilization from 32.3 to 35.9% compared with 50% forage diets. In Exp. 2 (70CS:30AH), feeding 60% forage diets decreased DMI from 29.6 to 28.2 kg but maintained the same level of milk (41.1 vs. 40.8 kg/d) and therefore increased the efficiency of converting feed to milk (1.46 vs. 1.38 kg milk/kg DMI) compared with 50% forage diets. Daily feed cost for feeding 60% forage diets was $0.3/head lower than for the 50% forage diets. Fecal excretion of DM (10.3 vs. 11.5 kg/d) was lower and fecal excretion of N (299 vs. 328 g/d) tended to be lower for 60% compared with 50% forage diets. Results from these 2 experiments suggest that a 60% forage diet consisting of either AS or CS as the major forage can be fed to high producing Holstein dairy cows without affecting milk production while improving or maintaining the efficiency of converting feed to milk and the apparent efficiency of utilization of feed N. Cows receiving a 60% forage diet had a similar or improved digestibility of nutrients with a similar or reduced fecal excretion of nutrients. Effects of monensin under the conditions of the current experiments were minimal.
Topics: Animal Nutritional Physiological Phenomena; Animals; Cattle; Dairying; Diet; Dietary Supplements; Digestion; Feces; Feeding Methods; Female; Lactation; Monensin; Nitrogen; Particle Size
PubMed: 19528598
DOI: 10.3168/jds.2008-1306 -
Journal of Medical Toxicology :... Sep 2017Monensin is a veterinary antibiotic with a narrow therapeutic window that has led to lethal intoxication in many animal species. Only two prior cases of human toxicity...
INTRODUCTION
Monensin is a veterinary antibiotic with a narrow therapeutic window that has led to lethal intoxication in many animal species. Only two prior cases of human toxicity have been reported, both fatal. We present the first case of survival from severe toxicity following monensin ingestion.
CASE
A 58-year-old man presented with 8 days of vomiting and abdominal pain. Due to delusions of central nervous system toxoplasmosis, he ingested 300 mg of monensin. His laboratory studies revealed severe rhabdomyolysis without renal dysfunction. Total creatine kinase (CK) peaked above 100,000 U/L. His CK decreased to 5192 U/L after 15 days of aggressive hydration and sodium bicarbonate therapy. His ejection fraction on echocardiogram decreased from 69 to 56%.
DISCUSSION
Reports on acute clinical effects after human exposure to monensin are limited. Ingestion is known to cause skeletal and cardiac muscle rhabdomyolysis and necrosis. Animal studies demonstrate that monensin's toxicity is due to increases in intracellular sodium concentrations and Ca release. To date, no effective antidotal treatment has been described.
CONCLUSIONS
Monensin is a veterinary medication not approved for human use by the US Food and Drug Administration. Though poorly studied in humans, this case demonstrates the severe harm that may occur following ingestion.
Topics: Anti-Bacterial Agents; Fatal Outcome; Humans; Male; Middle Aged; Monensin; Rhabdomyolysis; Severity of Illness Index; Veterinary Drugs
PubMed: 28516409
DOI: 10.1007/s13181-017-0616-6 -
Poultry Science Jul 2022Two experiments were conducted to evaluate the effects of dietary sophorolipids (SLs) supplementation as antibiotic alternatives on growth performance and gut health of...
Two experiments were conducted to evaluate the effects of dietary sophorolipids (SLs) supplementation as antibiotic alternatives on growth performance and gut health of chickens infected with Eimeria maxima. In experiment 1, 336 (zero-day-old) male broilers were used. The chickens were weighed and randomly allocated to the following 6 treatments groups with 7 chickens/cage and 8 cages/treatment: control group that received a basal diet (NC), positive control group that received a basal diet and was challenged with E. maxima (PC), PC+C18:1 lactonic diacetyled SL (SL1), PC+C18:1 deacetyled SL (SL2), PC+C18:1 monoacetyled SL (SL3), and PC+C18:1 diacetyled SL (SL4). Each SL (200 mg/kg feed) was added to the corresponding treatment group. In experiment 2, 588 (zero-day-old) male broilers were used. The chickens were randomly allocated to the following experimental groups with 10 or 11 chickens/cage and 8 cages/treatment: NC, PC, PC+ monensin at 90 mg/kg feed (MO), PC+SL1 at 200 mg/kg feed (SL1 200), PC+SL1 at 500 mg/kg feed (SL1 500), PC+SL4 at 200 mg/kg feed (SL4 200), and PC+SL4 at 500 mg/kg of feed (SL4 500). The chickens and feed were weighed at 0, 7, 14, 20, and 22 d to determine growth performance. In both experiments, all chickens except the NC group were orally infected with E. maxima (10,000 oocysts/chicken) at d 14. One chicken per cage was euthanized at d 20 to sample jejunal tissue to measure lesion scores, cytokines, and tight junction (TJ) proteins. Excreta samples were collected daily between d 20 and 22 to measure oocyst numbers. Data were analyzed using Mixed Model (PROC MIXED) in SAS. In experiment 1, SLs did not affect the growth of broiler chickens, but SL4 decreased (P < 0.05) the lesion score and oocyst number compared to PC chickens. In terms of cytokines and TJ protein gene expression, SLs increased (P < 0.05) IL-1β, IL-6, IL-17F, IL-4, IL-13, occludin, and ZO1 levels compared to PC chickens. In experiment 2, monensin increased (P < 0.05) body weight, and decreased (P < 0.05) the lesion score and oocyst number compared to the PC group. SL4 500 increased (P < 0.05) average daily gain and feed conversion ratio but decreased (P < 0.05) lesion score and fecal oocyst number. SL4 decreased (P < 0.05) IL-6, IL-17F, TNFSF-15, IL-2, and IL-10 levels but increased (P < 0.05) occludin and ZO-1 levels. Overall, dietary SL supplementation, especially SL4, improved growth and gastrointestinal functionality of young broiler chickens, demonstrating significant potential as an antibiotic alternative.
Topics: Animal Feed; Animals; Anti-Bacterial Agents; Chickens; Coccidiosis; Diet; Dietary Supplements; Eimeria; Interleukin-17; Interleukin-6; Intestines; Male; Monensin; Occludin; Oleic Acids; Oocysts; Poultry Diseases
PubMed: 35679665
DOI: 10.1016/j.psj.2022.101944