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PubMed1978

Enzymatic modification of aminoglycoside antibiotics: 3-N-acetyltransferase with broad specificity that determines resistance to the novel aminoglycoside apramycin.

Examination of a number of R-plasmid-containing bacterial isolates of animal origin has revealed the presence of a new aminoglycoside acetyltransferase (3-N) with a broad substrate range that includes all the disubstituted 2-deoxystreptamine antibiotics and also the novel monosubstituted antibiotic apramycin. Antibiotic derivatives acylated with hydroxyaminobutyric acid at the 1-amino position were not modified by the enzyme.

Acetyltransferases↗
PubMed1986

Emergence of aminoglycoside 3-N-acetyltransferase IV in Escherichia coli and Salmonella typhimurium isolated from animals in France.

We studied two outbreaks of calf salmonellosis caused by apramycin and gentamicin-resistant Salmonella typhimurium strains. In both cases, the responsible strains were resistant to ampicillin, chloramphenicol, kanamycin, streptomycin, tetracycline, and trimethoprim; one strain was also resistant to nalidixic acid in one outbreak. A systematic survey of the intestinal Escherichia coli strains of calves from the two affected flocks showed that 11 of 24 animals sampled were also colonized by apramycin- and gentamicin-resistant E. coli strains. These isolates belonged to four biotypes and were resistant to ampicillin, chloramphenicol, kanamycin, streptomycin, tetracycline, trimethoprim, and nalidixic acid. All of the strains were resistant to high levels of apramycin (MICs, 512 to 1,024 micrograms/ml) and to gentamicin (MICs, 8 to 32 micrograms/ml), and these resistances were always transferred en bloc. In S. typhimurium, this coresistance was borne by plasmids that were approximately 39 kilobases long (outbreak 1) or 90 kilobases long (outbreak 2), whereas in E. coli, the coresistance was due to plasmids that were approximately 110 kilobases long in both outbreaks. The two plasmids of Salmonella and four plasmids of E. coli encoded type IV aminoglycoside 3-N-acetyltransferases. The intensive use of curative and preventive treatments in calf production could be responsible for the emergence of enzymic resistance to apramycin and gentamicin.

Acetyltransferases↗
PubMed1990

Aminoglycoside acetyltransferase 3-IV (aacC4) and hygromycin B 4-I phosphotransferase (hphB) in bacteria isolated from human and animal sources.

Members of the family Enterobacteriaceae harboring an enzyme of the aminoglycoside acetyltransferase 3 class (AAC-3-IV) (apramycin and gentamicin resistance) and hygromycin B phosphotransferase 4 (HPH-4-I) (hygromycin B resistance) have been isolated from human clinical sources in Europe. A cluster of genes containing IS140, aacC4, and hphB was found in these strains. We demonstrate by Southern hybridization that this cluster is identical to the operon found in animals that also contains insertion sequences belonging to the ISO family. This provides another example of presumptive transfer of antibiotic resistance genes between bacteria of animal and human origin.

Acetylation↗
PubMed1991

High genetic homology between plasmids of human and animal origins conferring resistance to the aminoglycosides gentamicin and apramycin.

Escherichia coli and Salmonella strains resistant to gentamicin and apramycin were isolated from cattle in France and Belgium and from patients in hospitals. Homology between plasmids of both human and animal origins encoding aminoglycoside 3-N-acetyltransferase was revealed by digestion with several restriction endonucleases and confirmed by hybridization with different replicon-specific probes.

Animals↗
PubMed2001

Relative distribution and conservation of genes encoding aminoglycoside-modifying enzymes in Salmonella enterica serotype typhimurium phage type DT104.

PCR was used to identify genes encoding aminoglycoside-modifying enzymes in 422 veterinary isolates of Salmonella enterica serotype Typhimurium. The identities of extra-integron genes encoding resistance to streptomycin, gentamicin, kanamycin, and apramycin were evaluated. Gentamicin resistance was conferred by the aadB gene. Kanamycin resistance was encoded by either the aphA1-Iab gene or the Kn gene. Apramycin resistance was determined by the aacC4 gene. Analysis of gene distribution did not reveal significant differences with regard to phage type, host species, or region except for the Kn gene, which was found mostly in nonclinical isolates. The data from this study indicate that pentaresistant DT104 does not acquire extra-integron genes in species- or geography-related foci, which supports the hypothesis that clonal expansion is the method of spread of this organism.

Acetyltransferases↗
PubMed1990

Phenotypic suppression by aminoglycoside antibiotics of mutations blocking erythromycin biosynthesis in Saccharopolyspora erythraea.

The presence of a sublethal amount of apramycin, the aminoglycoside antibiotic used as a selectable marker in transformations of Saccharopolyspora erythraea with pKC505 and related plasmids, was found to suppress phenotypically the S. erythraea eryB25 and eryB26 mutations blocking erythromycin biosynthesis in this organism, probably by the effect of mistranslation.

Anti-Bacterial Agents↗
PubMed1991

Transposition of Tn5096 and other IS493 derivatives in Streptomyces griseofuscus.

Tn5096 was constructed by inserting an apramycin resistance gene, aac(3)IV, into IS493 from Streptomyces lividans. By using conventional and pulsed-field gel electrophoresis, Tn5096 and related transposons were shown to insert into many different locations in the Streptomyces griseofuscus chromosome and in two linear plasmids. On insertion into the target site CANTg, 3 bp appeared to be duplicated. Independent transpositions were obtained by delivery of the transposon from a temperature-sensitive plasmid. The frequency of auxotrophy among cultures containing transpositions was about 0.2%.

Anti-Bacterial Agents↗
PubMed1996

Apramycin resistance as a selective marker for gene transfer in mycobacteria.

We have explored the potential of using the apramycin resistance gene as a marker in mycobacterial gene transfer studies. Shuttle plasmids available for both electroporation and conjugation studies have been constructed, and we have successfully validated the use of the apramycin resistance gene as a component of cloning vectors for Mycobacterium smegmatis, M. bovis BCG, and M. tuberculosis.

Anti-Bacterial Agents↗
PubMed1997

Growth performance and intestinal microbial populations of growing pigs fed diets containing sucrose thermal oligosaccharide caramel.

Four experiments were conducted to determine growth performance and changes in intestinal microbial populations of growing pigs fed diets containing sucrose thermal oligosaccharide caramel (STOC). Ninety-six barrows and 96 gilts were group-fed experimental nursery diets for 32 d after weaning in both Exp. 1 and 2. For each experiment, pigs were divided into four groups of 48 pigs and were fed either control, antibiotic (Apramycin sulfate, 34 mg/kg), 1% STOC, or 2% STOC diets for 32 d after weaning. Each diet was replicated six times with eight pigs per replication. Pigs were either orally gavaged (Exp 1) with water of STOC (2 g per pig) or pigs were creep-fed (Exp 2) either a control diet or a 2% STOC diet for 5 d before weaning (33 d). At the end of Exp 1 and 2, cecal material was collected for enumeration of total aerobes, total anaerobes, coliforms, lactobacilli, and bifidobacteria. Gilts (96 per experiment) used in Exp. 3 and 4 were weaned at 26 d and fed experimental nursery diets for 32 d. They were fed either a control or 1% STOC diet and were otherwise treated as previously described. There were no significant effects of STOC or antibiotic on ADG, ADFI, feed efficiency, or cecal microbial populations in pigs in this study. Feeding diets containing either antibiotic of STOC did not improve animal performance or change intestinal bacterial populations in the present study.

Animals↗
PubMed1998

Incidence of antibiotic resistance in fecal Escherichia coli isolated from commercial swine farms.

Sows and pigs from 10 commercial swine farms were sampled to determine patterns of resistance of fecal Escherichia coli to five commonly used antibiotics. Before testing, farms were categorized as high or low antibiotic use based on interviews with the respective producers. On each farm, fecal swabs were obtained from five sows at 7 d postpartum and from five pigs from each sow at 7, 35, and 63 d of age. A total of 6,296 E. coli isolates from 750 pig fecal samples and a total of 462 E. coli isolates from 50 sow fecal samples were tested against apramycin, carbadox, gentamicin, neomycin, and oxytetracycline using a standardized disk diffusion test. Percentage of resistant organisms was compared between pigs at the various stages of growth, between sows and their respective pigs, and between farms of high and low antibiotic use. Incidence of resistance was greater (P < .05) in pigs at 35 or 63 d of age compared with 7 d of age for most antibiotics, and patterns differed between high-use and low-use farms. Resistance differed (P < .05) among E. coli from pigs compared to their respective sows for apramycin and carbadox on low-use farms, whereas incidence of resistance on high-use farms differed (P < .05) between sows and pigs for apramycin and oxytetracycline. These data indicate that patterns of antibiotic resistance are dependent on age of pig and level of antibiotic use.

Animals↗
PubMed2006

Effects of supplementation of beta-glucans on growth performance, nutrient digestibility, and immunity in weanling pigs.

Two experiments were conducted to evaluate the efficacy of beta-glucan on growth performance, nutrient digestibility, and immunity in weanling pigs. In Exp. 1, 210 weanling pigs (6.38 +/- 0.92 kg of BW) were fed dietary beta-glucan (0, 0.01, 0.02, 0.03, or 0.04%) for 5 wk. In Exp. 2, 168 pigs (6.18 +/- 1.31 kg of BW) were fed no beta-glucan or antibiotics (T1), 0.02% beta-glucan (T2), only antibiotics (T3), or 0.02% beta-glucan with antibiotics (T4) for 8 wk. In Exp. 2, the antibiotics fed were apramycin and carbadox in phase I (0 to 2 wk) and carbadox and chlortetracycline in phase II (3 to 8 wk). During Exp. 2, the performance study was conducted for 5 wk, and the immune response was tested until 8 wk. In Exp. 1, there was a trend for a linear increase (P = 0.068) in ADG as the dietary beta-glucan concentration increased in the diet. The digestibilities of DM, GE, CP, ether extract, Ca, and P increased linearly (P < 0.05) in the beta-glucan-supplemented pigs. In Exp. 2, the overall ADG was greater (P < 0.05) in treatment T4 compared with the control group (T1). Also, except for P, this group showed greater (P < 0.05) nutrient digestibilities than the control group. In Exp. 2, at d 15, 24, and 46 antibody titers were measured by ELISA against Pasteurella multocida type A and D after vaccination with atrophic rhinitis, and they differed significantly (P < 0.05) with no particular trend. Flow cytometry was used to determine porcine lymphocyte subpopulations at 4 and 8 wk of Exp. 2. There was an increase in CD4 cells (P < 0.05) and a trend for an increase in CD8 cells (P < 0.10) at 8 wk in pigs fed the T2 diet compared with the other groups. Overall, increasing the dietary concentrations of beta-glucan did not improve ADG without antibiotic, and in weanling pigs antibiotics seem to be more effective in improving nutrient digestibilities and growth performance than beta-glucan.

Animal Feed↗
PubMed2000

Effects of antibiotic regimens on the fecal shedding patterns of pigs infected with salmonella typhimurium.

An experiment was conducted to determine (i) the effects of antibiotic regimens on the shedding patterns of pigs infected with Salmonella Typhimurium and (ii) whether antibiotic resistance increases the incidence of pathogen shedding. The experiment involved 48 50-day-old pigs challenged with Salmonella Typhimurium and receiving one of four antibiotic regimens including (i) intramuscular injection of ceftiofur sodium followed by inclusion of oxytetracycline in the feed; (ii) apramycin in the feed for 14 days followed by oxytetracycline; (iii) carbadox in the feed until pigs reached 35 kg followed by oxytetracycline; (iv) no antibiotics (control). Fecal samples were collected preinoculation, 2 and 4 days postinoculation (DPI) and at weekly and biweekly intervals thereafter to determine shedding patterns. Salmonella Typhimurium isolates from 2, 4, 7, 21, 42, and 70 DPI were analyzed for antibiotic resistance. A time effect (P < 0.05) was observed, indicating that the proportion of isolates resistant to at least one antibiotic varied over time. Overall resistance was determined to be 46% at 2 DPI and increased significantly (P < .05) thereafter. Treatment x time and antibiotic x time interactions were also observed (P < 0.05) as the percentage of isolates resistant to each test antibiotic increased over time. In no case did the development of antibiotic resistance result in an increased incidence of shedding of the original inoculate. The incidence of shedding was reduced in pigs receiving the apramycin-oxytetracycline treatment, when compared to control pigs; however, no differences were observed between antibiotic treatments.

Animals↗
PubMed2001

Evaluation of subtherapeutic use of the antibiotics apramycin and carbadox on the prevalence of antimicrobial-resistant Salmonella infection in swine.

The antibiotics apramycin and carbadox were fed to growing swine, and the prevalence of Salmonella isolates that are resistant to apramycin and related aminoglycoside antibiotics was examined. Three hundred twelve Salmonella-positive pigs raised on one of five farms in an integrated swine operation and slaughtered at a central plant were used. All farms fed carbadox during the grower phase, and two farms administered apramycin during the first 21 days of age. Ileocolic lymph nodes and cecal contents were sampled at slaughter. One hundred of the 312 pigs were randomly selected to examine apramycin- and carbadox-resistant Salmonella infection, while all 312 pigs were used to evaluate the association between apramycin exposure and infection with Salmonella organisms resistant to amikacin, gentamicin, kanamycin, and streptomycin. Antimicrobial resistance was determined using disk diffusion and breakpoint concentrations. Apramycin treatment appeared to have little effect on apramycin- (12.5 versus 20.9%) or streptomycin- (76.4 versus 73.5%) resistant Salmonella isolates when averaged across farms and compared to control animals. Feeding carbadox resulted in carbadox-resistant Salmonella infection in only 5.3% of the isolates on one farm. The prevalence of amikacin-, gentamicin-, and kanamycin-resistant Salmonella isolates on farms feeding apramycin and carbadox were 0, 0, and 1.8%, respectively. Serogroup B was the most prevalent serogroup isolated, followed by C1 and E1. Apramycin and carbadox treatment did not appear to have any effect on the serogroup isolated. Subtherapeutic use of carbadox and apramycin did not appear to increase the prevalence of antimicrobial-resistant Salmonella in market-age swine.

Animals↗
PubMed1981

Aminoglycoside antibiotics. XIV. Synthesis and activity of 6-O-(3-amino-3-deoxy-alpha-D-glucopyranosyl)-and 5-O-(beta-D-ribofuranosyl)apramycins.

6-O-(3-Amino-3-deoxy-alpha-d-glucopyranosyl)apramycin (17) was prepared by glycosidation of a suitably blocked 5,6-dihydroxy derivative (11) of apramycin with a blocked 3-aminoglucosyl chloride (15). Ribosylation of the 5-hydroxy-6-O-tetrahydropyranyl (THP) derivative (19) of apramycin gave 5-O-(beta-d-ribofuranosyl)apramycin (24) along with the 6 alpha (25) and 6 beta (26) isomers. Similar reaction with the 6-hydroxy-5-O-THP derivative (20) or 11 gave only 25 and 26, but not 24. 17 was at least as active as apramycin against most Gram-positive and Gram-negative bacteria tested and more active than apramycin against most Gram-positive and Gram-negative bacteria tested and more active than apramycin against strains producing aminoglycoside-modifying enzymes. Strains of Pseudomonas aeruginosa were generally less sensitive to 17 than to apramycin. 24 was the most active of the three ribofuranosyl derivatives prepared though it was less active than 17.

Acetylation↗