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PubMed1989

Inducible ribosomal RNA methylation in Streptomyces lividans, conferring resistance to lincomycin.

Streptomyces lividans TK21 possesses inducible ribosomal RNA methylase activity that confers high-level resistance to lincomycin and lower levels of resistance to certain macrolides. The methylase gene (designated lrm) is inducible by erythromycin and other macrolides and also by celesticetin (a lincosamide) but not by lincomycin. The lrm enzyme monomethylates the N6-amino group of adenosine at position 2058 within 23S-like ribosomal RNA.

Anti-Bacterial Agents↗

PubMed1997

A 32 kb nucleotide sequence from the region of the lincomycin-resistance gene (22 degrees-25 degrees) of the Bacillus subtilis chromosome and identification of the site of the lin-2 mutation.

A 32 kb nucleotide sequence in the region of the lincomycin-resistance gene, located from 22 degrees to 25 degrees on the Bacillus subtilis chromosome, was determined. Among 32 putative ORFs identified, four [lipA for lipase, natA, natB and yzaE (renamed yccK)] have already been reported, although the functions of NatA, NatB and YccK remain to be characterized. Six putative products were found to exhibit significant similarity to known proteins in the databases, namely L-asparaginase precursor, protein aspartate phosphatase, alpha-glucosidase, two tellurite-resistance proteins and a hypothetical protein from B. subtilis. The region of the tellurite-resistance gene, consisting of seven ORFs, seems to correspond to an operon. The products of 14 ORFs exhibited considerable or limited similarity to known proteins. The sequenced region seems to be rich in membrane proteins, since at least 16 gene products appeared to contain membrane-spanning domains. The site of the lin-2 mutation (two nucleotide replacements) was mapped and identified by sequencing. This site is located between a putative promoter and the SD sequence of ImrA (yccB) [a putative repressor of the lmr operon, which consists of lmrA and lmrB (yccA)]. LmrB is a homologue of proteins involved in drug-export systems and seems likely to be the protein responsible for resistance to lincomycin.

Anti-Bacterial Agents↗

PubMed1978

Interaction between erythromycin and lincomycin in Streptococcus pyogenes.

Ten strains of Streptococcus pyogenes isolated were moderately resistant to erythromycin and highly but paradoxically resistant to lincomycin, and they showed antagonism between the two antibiotics. Another strain was moderately resistant to erythromycin and sensitive to lincomycin, and it showed synergism between the two antibodies.

Dose-Response Relationship, Drug↗

PubMed1986

The effect of lincomycin on exoprotein production by Vibrio cholerae.

Lincomycin has a differential effect on exoprotein production by Vibrio cholerae. The production of some proteins, such as cholera toxin and deoxyribonuclease, is stimulated by low concentrations of the drug while production of other proteins, such as protease and alkaline phosphatase, is unaffected. Possible mechanisms of the lincomycin effect are discussed.

Alkaline Phosphatase↗

PubMed1986

Chloramphenicol, lincomycin and oxytetracycline disposition in calves with experimental pneumonic pasteurellosis.

The effects of pneumonia on the pharmacokinetics of chloramphenicol, lincomycin, and oxytetracycline were evaluated in two-month-old calves. Pneumonia was induced by injection of Pasteurella haemolytica cultures directly through the thoracic wall into each lung. Six days prior to induction of pneumonia, the antibiotics were administered in a single i.v. dose. The antibiotics were administered again 48 (i.v.), 60 and 72 h (i.m.) following injection of P. haemolytica. The pharmacokinetics of chloramphenicol (25 mg/kg) and lincomycin (10 mg/kg) were not significantly different in calves with pneumonia. The hybrid rate constant beta for oxytetracycline was increased in calves with pneumonia from 0.0034 +/- 0.0003/min to 0.0048 +/- 0.0007/min between 2 h and 8 h. Thus the elimination half-life in serum was shortened from 212.4 +/- 20.3 min to 149.3 +/- 19.5 min. In addition, there was an apparent but not statistically significant decrease in K12 with pneumonia. These findings accentuate the need for observance of 12-h dose intervals with oxytetracycline.

Animals↗

PubMed1995

Molecular characterization of the lincomycin-production gene cluster of Streptomyces lincolnensis 78-11.

The lincomycin (LM)-production gene cluster of the overproducing strain Streptomyces lincolnensis 78-11 was cloned, analysed by hybridization, as well as by DNA sequencing, and compared with the respective genome segments of other lincomycin producers. The lmb/lmr gene cluster is composed of 27 open reading frames with putative biosynthetic or regulatory functions (lmb genes) and three resistance (lmr) genes, two of which, lmrA and lmrC, flank the cluster. A very similar overall organization of the lmb/lmr cluster seems to be conserved in four other LM producers, although the clusters are embedded in non-homologous genomic surroundings. In the wild-type strain (S. lincolnensis NRRL2936), the lmb/lmr-cluster apparently is present only in single copy. However, in the industrial strain S. lincolnensis 78-11 the non-adjacent gene clusters for the production of LM and melanin (melC) both are duplicated on a large (0.45-0.5 Mb) fragment, accompanied by deletion events. This indicates that enhanced gene dosage is one of the factors for the overproduction of LM and demonstrates that large-scale genome rearrangements can be a result of classical strain improvement by mutagenesis. Only a minority of the putative Lmb proteins belong to known protein families. These include members of the gamma-glutamyl transferases (LmbA), amino acid acylases (LmbC), aromatic amino acid aminotransferases (LmbF), imidazoleglycerolphosphate dehydratases (LmbK), dTDP-glucose synthases (LmbO), dTDP-glucose 4,6-dehydratases (LmbM) and (NDP-) ketohexose (or ketocyclitol) aminotransferases (LmbS). In contrast to earlier proposals on the biosynthetic pathway of the C-8 sugar moiety (methylthiolincosaminide), this branch of the LM pathway actually seems to be based on nucleotide-activated sugars as precursors.

ATP-Binding Cassette Transporters↗

PubMed1990

Treatment of virulent footrot with lincomycin and spectinomycin.

A mixture of lincomycin and spectinomycin was investigated as a treatment for footrot in sheep. In a controlled clinical trial 92.5% of acute and chronic cases of virulent footrot were cured following a single intramuscular injection of a mixture containing 50 mg lincomycin and 100 mg spectinomycin/ml at a dose rate of 1 ml/10 kg bodyweight. No improvement in clinical response was observed in groups of sheep treated on 3 successive days with this dose rate nor in another group treated once at a dose rate 1 ml/3.3 kg bodyweight. Cure effectiveness of each of the 3 treatment groups relative to untreated controls was 89%, 95% and 95%. Efficacy of lincomycin/spectinomycin was compared with that of penicillin/streptomycin in the treatment of footrot on 2 farms in south western New South Wales. Assessments made 14 to 17 d after treatment showed that on one farm all 122 ewes treated with lincomycin/spectinomycin had recovered while 170 of 175 ewes treated with penicillin/streptomycin recovered in the same period. On the second farm 87 of 90 ewes treated with lincomycin/spectinomycin recovered, compared with 184 of 190 sheep in the same flock treated with penicillin/streptomycin. Supportive footbathing did not seem to improve the clinical response in either treatment group and the paring done was sufficient only to establish diagnosis and to remove grossly overgrown horn.

Animals↗

PubMed1972

Activity of two chlorinated lincomycin analogues against chloroquine-resistant falciparum malaria in owl monkeys.

The chloroquine-resistant Oak Knoll strain of Plasmodium falciparum, recently adapted to the owl monkey (Aotus trivirgatus), was insusceptible to chloroquine therapy. Two chlorinated lincomycin analogues tested in this host-parasite system cured blood-induced infections. Acute infections were treated orally for 7 consecutive days with either 15 or 75 mg of clindamycin hydrochloride (U-21) per kg per day, 10 or 50 mg of N-demethyl-4'-pentyl clindamycin hydrochloride (U-24) per kg per day, or 20 mg of chloroquine base per kg per day. These lincomycin analogues cleared trophozoites from the peripheral blood by the end of the 7-day treatment period. The speed of clearance of parasites was not dose-related, but curative activity appeared dependent upon the amount of drug given as well as the number of daily treatments. The efficacy of U-21 and U-24 is of particular interest since they represent major structural departures from compounds commonly used in the treatment of malaria.

Animals↗

PubMed1982

Effect of clindamycin, erythromycin, lincomycin, and tetracycline on growth and extracellular lipase production by propionibacteria in vitro.

Two propionibacteria identified as Propionibacterium acnes and Propionibacterium granulosum were grown anaerobically in the presence of growth subinhibitory concentrations (0.25 and 0.5 minimal inhibitory concentrations) of clindamycin, erythromycin, lincomycin, and tetracycline. Viable counts and assays of extracellular lipase were performed on samples taken at 24-h intervals over a 96-h period. The results showed that lincomycin and clindamycin could inhibit the production of the enzyme by both strains with little effect on their growth rates. Tetracycline caused inhibition of lipase production by P. granulosum only. Although production of the enzyme by P. acnes was delayed in the presence of tetracycline, the final titer was the same as the control. Erythromycin had little effect on growth and enzyme production of either strain. It is possible, therefore, that certain antibiotics used in acne therapy may act not only as bactericidal agents but also as inhibitors of enzyme production under non-growth-limiting conditions.

Clindamycin↗

PubMed1973

Inducible and constitutive resistance to macrolide antibiotics and lincomycin in clinically isolated strains of Streptococcus pyogenes.

STUDIES ON ERYTHROMYCIN RESISTANCE IN STRAINS OF GROUP A STREPTOCOCCI INDICATED THAT THEY WERE COMPRISED OF TWO TYPES: (i) an inducible, resistant type (IR strains) was seen, which manifested immediate logarithmic growth in media containing high concentrations of the drug only after brief previous exposure (induction period) of the organisms to subinhibitory concentrations of erythromycin, and (ii) a constitutive, resistant type (CR strains) which demonstrated, without prior drug exposure, continued logarithmic growth in media containing high concentrations of erythromycin. Subinhibitory concentrations of either chloramphenicol or puromycin, when added to IR strains prior to induction, interfered with their induction by erythromycin. Exposure of CR strains to chloramphenicol did not visibly affect the subsequent growth curve of these strains in media containing high concentrations of erythromycin. In IR strains, resistance to other macrolide antibiotics (oleandomycin, spiramycin, carbomycin, magnamycin) and to lincomycin also was inducible in nature. There was cross-inducibility between erythromycin, other macrolide antibiotics, and lincomycin. CR strains were constitutively resistant to these antibiotics.

Anti-Bacterial Agents↗

PubMed1983

Production of cholera toxin-like toxin by Vibrio mimicus and non-O1 Vibrio cholerae: batch culture conditions for optimum yields and isolation of hypertoxigenic lincomycin-resistant mutants.

Vibrio mimicus 61892, isolated in 1977 from a case of watery diarrhea in Bangladesh, produces an enterotoxin which possesses activity in Y-1 mouse adrenal cells and in rabbit ileal loops which is identical to the prototype cholera toxin (CT) produced by Vibrio cholerae 569B. The neutralization of the adrenal cell activity of 61892 toxin and 569B CT by homologous and heterologous antisera generates parallel titration curves which show complete neutralization in all cases. Paired titrations in the ganglioside GM1 enzyme-linked immunosorbent assay (using either CT or Escherichia coli heat-labile toxin antitoxin) of both toxins indicates that 61892 toxin is antigenically indistinguishable from 569B CT. The specific activity of the two toxins in the rabbit ileal loop is virtually identical. Batch culture production of CT-like toxin and CT by isolates of V. mimicus and different biotypes of V. cholerae was found to be highest in shake flask cultures of Casamino Acids-yeast extract broth grown at 27 degrees C with vigorous aeration. Incorporation of lincomycin into the growth medium at a concentration of 50 micrograms/ml increased yields from wild-type strains. Dramatically higher yields were obtained when a spontaneous resistance mutant of strain 61892 was grown in the presence of 200 to 300 micrograms of lincomycin per ml. Under these conditions, yields of CT-like toxin were increased by 300- to 500-fold, and the highest yields reached more than 100 micrograms/ml after 44 h of culture. This is substantially higher than that reported in the literature for CT production by any strain of V. cholerae, including hypertoxigenic strain 569B.

Bacterial Toxins↗

PubMed1972

Lincomycins in the treatment of bacteroides infections.

Lincomycin, or the closely related derivative clindamycin, was used to treat six patients with bacteroides infection. In five of the six there was a rapid clinical response to the treatment. Lincomycin and clindamycin seem to be the antibiotics of choice for such infections.

Adolescent↗

PubMed1969

Clinical trial of lincomycin hydrochloride in Reiter's disease.

A double-blind trial comparing lincomycin hydrochloride (Mycivin) and placebo in 22 patients with Reiter's disease showed no significant difference in clinical or laboratory findings between the two groups. It is concluded that lincomycin hydrochloride is no more effective than placebo in the treatment of Reiter's disease.

Adult↗

PubMed1968

Trial of phenoxymethylpenicillin, phenethicillin, and lincomycin in treatment of staphylococcal sepsis in a casualty department.

A comparative trial of phenoxymethylpenicillin (penicillin V), phenethicillin (Broxil), and lincomycin (Lincocin) against superficial staphylococcal infections seen in a casualty department showed no difference in the efficacy of the three agents, though half the staphylococci isolated were resistant to penicillin. Possible reasons include the fact that antibiotic treatment may not affect superficial staphylococcal infections, or that the organisms concerned may have been weak formers of penicillinase.Half the patients treated with lincomycin complained of diarrhoea and 5% of those treated with phenethicillin suffered from nausea.

Adolescent↗

PubMed1975

Effect of lincomycin on lipase formation by Staphylococcus aureus.

The production of Staphylococcus aureus lipase could be inhibited by addition of 0.1 mug/ml lincomycin to the media without affecting growth. Addition of the same amount of drug at various stages of growth inhibited further enzyme production. The enzymatic activity of the lipase could not be inhibited at a concentration of 2.5 mug/ml lincomycin.

Enzyme Activation↗

PubMed1995

Influence of the antibiotics lincomycin and tylosin on aflatoxicosis when added to aflatoxin-contaminated diets of growing swine.

Effects of dietary aflatoxin (AF) and the antibiotics lincomycin (L) and tylosin (T) were evaluated in growing crossbred pigs. Six barrows (3 replicates of 2 each, mean body weight 14.0 kg) per group were assigned to 1 of 6 treatment groups (for a total of 36): 0 mg L, 0 mg T, and 0 mg AF/kg of feed (control); 220 mg L/kg of feed (200 g/ton); 110 mg T/kg of feed (100 g/ton); 2.5 mg AF/kg of feed; 2.5 mg AF plus 220 mg L/kg of feed; 2.5 mg AF plus 110 mg T/kg of feed. Barrows were administered their respective diets for 28 days. Body weight, body weight gain, and feed consumption were reduced by the AF alone, the AF plus L, and the AF plus T treatments, compared with control, L, and T treatments. Altered serum biochemical or hematologic measurements induced by AF treatments included increased serum activities of alkaline phosphatase and gamma-glutamyltransferase, increased hematocrit, hemoglobin, RBC count, WBC count, and mean cell hemoglobin, decreased serum concentrations of albumin, cholesterol, inorganic phosphorus, unsaturated iron binding capacity, total protein, and urea nitrogen, and decreased lymphoblastogenic response. Liver weight was increased, and microscopic lesions were consistent with those observed in cases of aflatoxicosis. With some other minor exceptions for hematologic and immunologic variables, these data indicate that the feed antibiotics lincomycin and tylosin, when added to aflatoxin-contaminated diets, do not have beneficial or detrimental effects on aflatoxicosis in growing swine.

Aflatoxins↗

PubMed1979

Effects of cloxacillin, doxycycline, fusidic acid and lincomycin on the mechanical properties of bone and skin in young rats.

The influence of cloxacillin, doxycycline, fuside acid and lincomycin on the mechanical properties of bone and skin in young rats was examined. The concentrations of the antibiotics in plasma corresponded to therapeutic levels in man. After 14 days of medication the weights of the rats receiving cloxacillin or doxycycline were significantly less when compared with the controls. The doxycycline, the fusidic acid and the lincomycin treated rats had reduced longitudinal growth of femur and reduced tensile strength of intact skin. No differences between any of the antibiotic groups and the control group were found in the tensile strength of incisional skin wounds or in the mechanical properties of the femur and tibia.

Animals↗

PubMed1977

Comparison of therapeutic efficacy of doxycycline, chlortetracycline and lincomycin-spectinomycin on E. coli infection of young chickens.

Three replicate trials were conducted with broiler male chicks to test the therapeutic efficacy of doxycycline, chlortetracycline and lincomycin-spectinomycin in water against an artifically induced Escherichia coli infection. Mortality, lesion scores (heart, liver and air sac), and performance data were the criteria in evaluating therapeutic efficacy of these drugs. Results indicated the therapeutic efficacy of doxycycline was greater than chlortetracycline and lincomycin-spectinomycin.

Administration, Oral↗