Variacin, a new lanthionine-containing bacteriocin produced by Micrococcus varians: comparison to lacticin 481 of Lactococcus lactis.

A new lanthionine-containing bacteriocin, variacin, displaying a broad host range of inhibition against gram-positive food spoilage bacteria, has been identified from two strains of Micrococcus varians isolated from meat fermentations. The new bacteriocin was purified, and its amino-terminal end and total amino acid composition were determined. The structural gene was isolated and analyzed. Variacin is resistant to heat and pH conditions from 2 to 10. Its primary sequence shows significant homology to lacticin 481 to Lactococcus lactis, which is more pronounced for the probacteriocin than for the leader sequence. Variacin, like lacticin 481, contains lanthionine and beta-methyllanthionine residues, but its leader sequence clearly resembles nonlantibiotic leader sequences. In particular, the prepeptide contains glycine residues at positions -1 and -2 of the processing site.     

Gluconimycin,a new antibiotic

Summary A new antibiotic, gluconimycin, was isolated from Streptomyces AS 9. The systematic position of the organism is discussed. Gluconimycin has a polypeptide nature. It contains iron and gluconic acid in its molecule. Thus it has been classified as a member of sideromycins. Gluconimycin is considered from the fast moving type when chromatographed by butanolacetic acid-water. The antibiotic is active against Gram+ve, Gram-ve bacteria and some fungi. The antibiotic exerts high toxicity when injected in mice.     

Mecillinam: a new antibiotic for enteric fever.

Mecillinam is a new antibiotic related to the penicillins but more active than ampicillin against salmonellae, including Salmonella typhi. Mecillinam must be administered parenterally, but the ester, pivmecillinam, is absorbed from the gut. Eight patients suffering from typhoid fever and one suffering from paratyphoid fever were treated with the antibiotic, and seven responded satisfactorily. One patient could not tolerate pivmecillinam because of vomiting but there were no other adverse reactions. Serum and bile levels of mecillinam were many times the minimum inhibitory concentrations for most salmonellae. The antibiotic is a promising addition to the agents available for treating typhoid.     

A new streptomycete and a new polyene antibiotic,acmycin

A new antifungal antibiotic named acmycin was isolated from a soil streptomycete. Detailed comparative taxonomic studies showed that the organism differed from three related species of streptomycetes. The organism was referred to asStreptomyces sp. AC₂. The isolated antibiotic appears to be of polyene nature.     

Synthesis of a new inhibitor of the UDP-GalNAc:polypeptide galactosaminyl transferase

Reaction of UDP-glucose with 1-hexadecanesulfonyl chloride (C16H33SO2Cl) in pyridine gave a new inhibitor of O-glycosylation. This reaction product was purified by TLC and shown by 1H-NMR and by chemical analysis of phosphorus to be uridine 5'-phosphoric (1-hexadecanesulfonic) anhydride. This compound was tested against the GalNAc transferase. The UMP-hexadecanesulfonic-anhydride did inhibit this enzyme with 50% inhibition requiring 160 microM. The inhibition with respect to UDP-GalNAc concentration was of the competitive type. We also synthesized the UMP-1-octanesulfonic anhydride (C8) and the UMP-butanesulfonic anhydride (C4) to see way effect fatty acid had on activity. The inhibition was in the order C16:C8:C4.     

Fermentation and isolation of epidermin,a lanthionine containing polypeptide antibiotic from Staphylococcus epidermidis

Summary Staphylococcus epidermidis TÜ 3298/DSM 3095 produces epidermin, a basic 21-residue peptide-amide antibiotic active against aerobic and anaerobic Gram-positive bacteria. Fermentations were performed by batch and feeding processes up to the 2001 scale. Highest yields were obtained when the first purification step was integrated into the fermentation process by on-line adsorption of the antibiotic. Isolation and purification by adsorption chromatography and ion exchange chromatography were performed batchwise.     

UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-6 as a new immunohistochemical breast cancer marker.

Mucin O-glycosylation is characterized in cancer by aberrant expression of immature carbohydrate structures (Tn, T, and sialyl-Tn antigens). The UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-T) family enzymes regulate the initial steps of mucin O-glycosylation and could be responsible for the altered glycosylation observed in cancer. Considering that we recently found the ppGalNAc-T6 mRNA expressed in breast carcinomas, we produced a highly specific monoclonal antibody (MAb T6.3) to assess the expression profile of ppGalNAc-T6 protein product in breast tissues. The expression of ppGalNAc-T6 by breast carcinoma cells was confirmed on MCF-7 and T47D cell lines. In formalin-fixed tissues, ppGalNAc-T6 expression was observed in 60/74 (81%) breast cancers, 21/23 (91.3%) adjacent ductal carcinoma in situ (DCIS), 4/20 benign breast lesions (2/2 sclerosing adenosis and 2/13 fibroadenoma), and in 0/5 normal breast samples. We observed a statistically significant association of ppGalNAc-T6 expression with T1 tumor stage. This fact, as well as the observation that ppGalNAc-T6 was strongly expressed in sclerosing adenosis and in most DCIS, suggests that ppGalNAc-T6 expression could be an early event during human breast carcinogenesis. Considering that an abnormal O-glycosylation greatly contributes to the phenotype and biology of breast cancer cells, ppGalNAc-T6 expression could provide new insights about breast cancer glycobiology.     

Roflamycoin--a new channel-forming antibiotic

Ion permeability of lipid bilayers was studied in the presence of a new antifungal pentaene antibiotic, roflamycoin, the structure of which differs considerably from that of the well-known polyene channel-former amphotericin B. Both of them, however, show the property of increasing the membrane permeability only in the case of sterol-containing membrane when added on both its sides. The conductance is strongly dependent on the concentration of the antibiotic in the solutions and of sterol in the membrane. Unlike the amphotericin B channels, roflamycoin channels are potential-dependent and have short lifetime (approx. 1 s) and high conductance (approx. 100 ps in 1 M KCl), which increases linearly with the salt concentration and is not blocked by the familiar blockers of amphotericin B channels. The two antibiotics seem to have a common mechanism of channel formation, viz. the formation starts from two semi-pores assembled in the opposite monolayers from several molecules of the antibiotic and sterol. However, the inner diameter of the roflamycoin channel is larger because of the different antibiotic-to-sterol ratio in the channel aggregate. It is believed that the difference in the ratio is due to the presence of the methyl group in the polyene chain of roflamycoin, and the considerable difference in lifetimes of the two types of channels depends on the terminal groups of the antibiotics.