The effect of streptomycin, oxytetracycline, tilmicosin and phenylbutazone on spermatogenesis in bulls.
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To determine whether declining semen quality associated with health problems may be due to certain antibiotic or anti-inflammatory treatments, semen was collected 3 times per week for up to 42 d from 6 normal bulls after treatment with oxytetracycline, tilmicosin, dihydrostreptomycin, or phenylbutazone. No adverse effects on semen quality were observed. (+info)
A comparison of florfenicol and tilmicosin for the treatment of undifferentiated fever in feedlot calves in western Canada.
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A field trial was performed under commercial feedlot conditions in western Canada to compare the efficacy of florfenicol and tilmicosin for the treatment of undifferentiated fever (UF) in calves that received metaphylactic tilmicosin upon arrival at the feedlot. One thousand and eighty recently weaned, auction market derived, crossbred beef calves suffering from UF were allocated to one of 2 experimental groups as follows: florfenicol, which was intramuscular (i.m.) florfenicol administered at the rate of 20 mg/kg body weight (BW) at the time of allocation (Day 0) and again 48 h later, or tilmicosin, which was subcutaneous (s.c.) tilmicosin administered once at the rate of 10 mg/kg BW on day 0. Five hundred and forty-four animals were allocated to the florfenicol group and 536 animals were allocated to the tilmicosin group. The chronicity, wastage, overall mortality, and bovine respiratory disease (BRD) mortality rates were significantly (P < 0.05) lower in the florfenicol group than in the tilmicosin group. There were no significant (P > or = 0.05) differences in first UF relapse, second UF relapse, hemophilosis mortality, or miscellaneous mortality rates between the florfenicol and tilmicosin groups. Average daily gain (ADG) from arrival at the feedlot to the time of implanting and ADG from allocation to the time of implanting were significantly (P < 0.05) lower in the florfenicol group as compared with the tilmicosin group. There were no significant (P > or = 0.05) differences in arrival weight, allocation weight, implanting weight, or ADG from arrival to allocation between the experimental groups. In the economic analysis, there was an advantage of $18.83 CDN per animal in the florfenicol group. The results of this study indicate that florfenicol is superior to tilmicosin for the treatment of UF because of lower chronicity, wastage, overall mortality, and BRD mortality rates. However, interpretation of these observations must take into consideration the fact that these calves received meta-phylactic tilmicosin upon arrival at the feedlot, which is a standard, cost-effective, management procedure utilized by feedlots in western Canada. (+info)
The tylosin biosynthetic cluster from Streptomyces fradiae: genetic organization of the left region.
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The genetic organization of the left edge (tyIEDHFJ region) of the tylosin biosynthetic gene cluster from Streptomyces fradiae has been determined. Sequence analysis of a 12.9 kb region has revealed the presence of 11 ORFs, 10 of them belonging to the biosynthetic cluster. The putative functions of the proteins encoded by these genes are as follows: peptidase (ORF1, ddcA), tylosin resistance determinant (ORF2, tlrB), glycosyltransferase (ORF3, tylN), methyltransferase (ORF4, tylE), ketoreductase (ORF5, tylD), ferredoxin (ORF6, tylH2), cytochrome P450 (ORF7, tylH1), methyltransferase (ORF8, tylF), epimerase (ORF9, tylJ), acyl-CoA oxidase (ORF10, tylP) and receptor of regulatory factors (ORF11, tylQ). The functional identification of the genes in the proposed tylosin biosynthetic pathway has been deduced by database searches and previous genetic complementation studies performed with tylosin idiotrophic mutants blocked at various stages in tylosin biosynthesis. The tlrB gene has been shown to be useful as a tylosin resistance marker in Streptomyces lividans, Streptomyces parvulus and Streptomyces coelicolor and the effect of tylF on macrocin depletion has been confirmed. A pathway for the biosynthesis of 6-deoxy-D-allose, the unmethylated mycinose precursor, involving the genes tylD, tylJ and tylN is proposed. (+info)
From vanA Enterococcus hirae to vanA Enterococcus faecium: a study of feed supplementation with avoparcin and tylosin in young chickens.
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Fifteen newborn chickens were isolated in separate cages after 1 month of living together, divided into three groups, and challenged for 5 weeks with seed food which either was supplemented with avoparcin (10 mg/kg of animal food) or tylosin (40 mg/kg) or was nonsupplemented. At 9 weeks of age and after the 5-week challenge, all chickens received nonsupplemented feed for 4 additional weeks. At 4, 9, and 13 weeks of life, feces were collected and inoculated on M-Enterococcus agar plates with and without vancomycin (4 micrograms/ml). vanA-containing Enterococcus hirae was isolated from 11 of 15 chickens before antibiotic challenge, without detection of vancomycin-resistant Enterococcus faecium. At 9 weeks of age and after the 5-week avoparcin challenge, vanA E. hirae strains were no longer detected, but five of five chickens now had vanA E. faecium. At a lower frequency, vanA E. faecium had also displaced vanA E. hirae in both the tylosin group (one of four chickens) and the control group (two of five chickens). One month after avoparcin discontinuation, the number of chickens colonized with vanA E. faecium decreased from five to one. All vanA-containing E. hirae strains detected in the first month of life and most of the vanA-containing E. faecium strains detected in the second month of life showed identical ApaI and SmaI restriction patterns, respectively, when analyzed by pulsed-field gel electrophoresis. All vanA E. hirae isolates transferred glycopeptide and macrolide resistance to Enterococcus faecalis JH2-2 in vitro; the level of glycopeptide resistance was higher in the transconjugants than in the donor E. hirae strains. These data suggest that E. hirae may be a significant source of vanA determinants with the potential of transfer to other enterococcal species from humans or animals. (+info)
Impact of thioesterase activity on tylosin biosynthesis in Streptomyces fradiae.
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BACKGROUND: The polyketide lactone, tylactone, is produced in Streptomyces fradiae by the TylG complex of five multifunctional proteins. As with other type I polyketide synthases, the enzyme catalysing the final elongation step (TylGV) possesses an integral thioesterase domain that is believed to be responsible for chain termination and ring closure to form tylactone, which is then glycosylated to yield tylosin. In common with other macrolide producers, S. fradiae also possesses an additional thioesterase gene (orf5) located within the cluster of antibiotic biosynthetic genes. The function of the Orf5 protein is addressed here. RESULTS: Disruption of orf5 reduced antibiotic accumulation in S. fradiae by at least 85%. Under such circumstances, the strain accumulated desmycosin (demycarosyl-tylosin) due to a downstream polar effect on the expression of orf6, which encodes a mycarose biosynthetic enzyme. High levels of desmycosin production were restored in the disrupted strain by complementation with intact orf5, or with the corresponding thioesterase gene, nbmB, from S. narbonensis, but not with DNA encoding the integral thioesterase domain of TylGV. CONCLUSIONS: Polyketide metabolism in S. fradiae is strongly dependent on the thioesterase activity encoded by orf5 (tylO). It is proposed that the TylG complex might operate with a significant error frequency and be prone to blockage with aberrant polyketides. A putative editing activity associated with TylO might be essential to unblock the polyketide synthase complex and thereby promote antibiotic accumulation. (+info)
Bacterial flora of liver abscesses in feedlot cattle fed tylosin or no tylosin.
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Bacterial flora of liver abscesses from cattle fed tylosin or no tylosin and susceptibilities of the predominant bacterial isolates to tylosin and other antimicrobial compounds were determined. Abscessed livers were collected at slaughter from cattle originating from feedlots that had fed tylosin (n = 36) or no tylosin (n = 41) for at least 2 yr, and segments of livers with one or two intact abscesses were transported to the laboratory. Abscesses were cultured for anaerobic and facultative bacteria. Fusobacterium necrophorum, either as single culture or mixed with other bacteria, was isolated from all abscesses. The incidence of subsp. necrophorum, as part of the mixed infection, was lower (P < .05) in the tylosin group than in the no-tylosin group (33 vs 61%). However, the incidence of Actinomyces pyogenes was higher (P < .01) in the tylosin group than in the no-tylosin group (53 vs 10%). Totals of 119 F. necrophorum and 21 A. pyogenes isolates were used for determinations of susceptibilities to bacitracin, oxytetracycline, chlortetracycline, lasalocid, monensin, tylosin, tilmicosin, and virginiamycin. The minimum inhibitory concentrations (MIC) of antibiotics were determined with a broth microdilution method. The mean MIC of tylosin for F. necrophorum and A. pyogenes were not different between isolates from tylosin and no-tylosin groups. We concluded that continuous feeding of tylosin did not induce resistance in F. necrophorum or A. pyogenes. Also, the higher incidence of mixed infection of F. necrophorum and A. pyogenes in liver abscesses of tylosin-fed cattle suggests a potential synergistic interaction between the two organisms in causing liver abscesses. (+info)
Molecular analysis of tlrB, an antibiotic-resistance gene from tylosin-producing Streptomyces fradiae, and discovery of a novel resistance mechanism.
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The tlrB gene, which confers inducible resistance to a range of macrolide antibiotics including biosynthetic precursors of tylosin, was isolated and sequenced. In the genome of Streptomyces fradiae, it lies between pbp, which encodes a putative penicillin-binding protein, and tylN, encoding a glycosyltransferase involved in tylosin biosynthesis. The TlrB protein was produced in E. coli as a fusion to MalE. The fusion protein, but not MalE alone, inactivates macrolides in the presence of S-adenosyl-methionine (SAM) but the modified product(s) has not been characterised. (+info)
Multiple regulatory genes in the tylosin biosynthetic cluster of Streptomyces fradiae.
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BACKGROUND: The macrolide antibiotic tylosin is composed of a polyketide lactone substituted with three deoxyhexose sugars. In order to produce tylosin efficiently, Streptomyces fradiae presumably requires control mechanisms that balance the yields of the constituent metabolic pathways together with switches that allow for temporal regulation of antibiotic production. In addition to possible metabolic feedback and/or other signalling devices, such control probably involves interplay between specific regulatory proteins. Prior to the present work, however, no candidate regulatory gene(s) had been identified in S. fradiae. RESULTS: DNA sequencing has shown that the tylosin biosynthetic gene cluster, within which four open reading frames utilise the rare TTA codon, contains at least five candidate regulatory genes, one of which (tylP) encodes a gamma-butyrolactone signal receptor for which tylQ is a probable target. Two other genes (tylS and tylT) encode pathway-specific regulatory proteins of the Streptomyces antibiotic regulatory protein (SARP) family and a fifth, tylR, has been shown by mutational analysis to control various aspects of tylosin production. CONCLUSIONS: The tyl genes of S. fradiae include the richest collection of regulators yet encountered in a single antibiotic biosynthetic gene cluster. Control of tylosin biosynthesis is now amenable to detailed study, and manipulation of these various regulatory genes is likely to influence yields in tylosin-production fermentations. (+info)