Lincomycin

The lincomycin (LM)-production gene cluster of the overproducing strain Streptomyces iincolnensis 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 γ-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.

Antibiotic molecules have been reported among the xenobiotics present at trace levels in sewage treatment plant (STP) effluents and aquatic environment. Lincomycin, one of the most used in clinical practices whose presence in the STP effluents has been often documented, is submitted to an extensive investigation to assess its persistence in the environment and toxicity towards different algal strains. The possibility to remove the lincomycin from water by means of ozonation is demonstrated and a reduction of toxicity of ozonated solutions on S. leopoliensis, with respect to untreated solutions containing this compound, is obtained even just for 1 h of treatment. Kinetic constants for the attack to lincomycin of ozone (from 1.53×105 M−1 s−1 at pH=3.0 and 4.93×105 M−1 s−1 at pH=6.7) and OH radicals (4.37×109 M−1 s−1 at pH=5.5 and 4.59×109 M−1 s−1 at pH=7.5) are also evaluated.

The objective of this study was to observe the dynamics of clinical cure and recurrence of the lesions of bovine digital dermatitis for 11 months after treatment with topical lincomycin HCl. The study was a clinical follow-up of 39 active bovine digital dermatitis lesions (from 29 cows).Cows with active, painful bovine digital dermatitis (BDD) lesions on the interdigital commissure of the rear feet were identified on day 0. On day 1, lesions in all cows were photographed and full-skin thickness 6 mm punch biopsies were obtained for histological evaluation. All lesions on all cows were treated with topical lincomycin paste under a light bandage. On days 12 and 23, a subsample of 10 lesions was randomly selected, photographed, and biopsied. On day 37, all lesions on all cows were photographed and biopsied. After day 37, lesions were evaluated on a monthly basis. All lesions were photographed at each observation until day 341 (end of study) but only cows that had macroscopically active lesions were biopsied.Of the 39 lesions treated on day 1, 21 (54%) required re-treatment on at least one occasion before day 341. Macroscopic classification agreed well with histological classification when lesions were small, focal and active (M1 lesions) or large, ulcerative and active (M2), but agreement was variable for lesions that had healed macroscopically (M5) or that were chronic (M4). A transition model showed that M1 and M2 lesions were 27 times more likely to be an M2 lesion on the next observation than to be a healed (M5) lesion.