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Plasmid-encoded resistance to macrolides and lincosamides in Staphylococcus hyicus.

A small plasmid of 2.35 kb, isolated from a porcine Staphylococcus hyicus-culture, was found to be responsible for constitutive resistance to macrolide/lincosamide antibiotics. This plasmid-encoded property could be established by interspecific transformation experiments. The plasmid from porcine Staph. hyicus was designated as pSE2. It differed on the basis of its restriction map from the macrolid/lincosamid resistance (MLR-)-plasmids of other staphylococcal species from infections of humans. Furthermore, the pSE2 plasmid encoded two proteins of approximately 20.5 and 30 kDa.

Animals↗

abaB, a putative regulator for secondary metabolism in Streptomyces.

A chromosomal DNA fragment from Streptomyces antibioticus ATCC11891 was isolated by its ability to stimulate actinorhodin and undecylprodigiosin biosynthesis in Streptomyces lividans TK21. This fragment includes two open reading frames, whose deduced translated products resemble enzymes involved in sulfur metabolism (ORF1) and LysR-type transcriptional regulators (ORF2). The cloning of the promoter region of ORF2 (abaB) in high copy number led to overproduction of both antibiotics suggesting that this phenotype might well be due to titration by this region of one or more proteins. Southern blot analysis revealed that abaB gene is highly conserved among all streptomycetes tested.

Anti-Bacterial Agents↗

Identification of Escherichia coli clinical isolates producing macrolide 2'-phosphotransferase by a highly sensitive detection method.

Macrolide is inactivated with ATP plus crude extract of Escherichia coli producing macrolide 2'-phosphotransferase (MPH(2')), but not by living cells. Therefore, a convenient method for detection of MPH(2') using intact cells is needed. In this report, we determine that the modified lysozyme-DNase-RNase (LDR) method (named ELDR method) is at least one hundred times more sensitive for the detection of MPH(2') activity than the LDR method and, in addition, highly sensitive for the detection of aminoglycoside-modifying enzymes. Therefore, three new MPH(2')-producing strains were found in clinically isolated E. coli in Japan in 1997 by this method. It suggests that MPH(2')-producing E. coli have been spread in Japanese clinical fields.

Anti-Bacterial Agents↗

Engineered biosynthesis of a complete macrolactone in a heterologous host.

Macrocyclic polyketides have been subjects of great interest in synthetic and biosynthetic chemistry because of their structural complexity and medicinal activities. With expression of the entire 6-deoxyerythronolide B synthase (DEBS) (10,283 amino acids) in a heterologous host, substantial quantities of 6-deoxyerythronolide B (6dEB), the aglycone of the macrolide antibiotic erythromycin, and 8,8a-deoxyoleandolide, a 14-membered lactone ring identical to 6dEB except for a methyl group side chain in place of an ethyl unit, were synthesized in Streptomyces coelicolor. The biosynthetic strategy utilizes a genetic approach that facilitates rapid structural manipulation of DEBS or other modular polyketide synthases (PKSs), including those found in actinomycetes with poorly developed genetic methods. From a technological viewpoint, this approach should allow the rational design of biosynthetic products and may eventually lead to the generation of diverse polyketide libraries by means of combinatorial cloning of naturally occurring and mutant PKS modules.

Acyl Coenzyme A↗

In vitro activity of YM133, a new semisynthesized macrolide.

YM133, the 4"-O-(4-methoxyphenyl)acetyltylosin, is a new macrolide. The in vitro activity of YM133 was compared with those of erythromycin, josamycin, and rokitamycin by an agar dilution method. YM133 inhibited 90% of the tested isolates of Streptococcus pneumoniae, Legionella spp., and anaerobic bacteria at less than or equal to 1.56 micrograms/ml. The drug inhibited 90% of erythromycin-resistant staphylococci and Streptococcus pyogenes at less than or equal to 50 micrograms/ml. YM133 showed activity against erythromycin-, josamycin-, and rokitamycin-resistant (MIC greater than or equal to 100 micrograms/ml) strains of staphylococci, streptococci, Bacteroides spp., and Clostridium spp. Enterococci were less susceptible to other YM133-like macrolides. Unlike other macrolides, YM133 showed killing activity, and the MBC/MIC ratios of YM133 for several strains were 1:32, whereas those of erythromycin were 4:1,024. In a time-kill curve study, the reduction of viable cells started within 2 h after the addition of YM133.

Anti-Bacterial Agents↗

In vitro activity of doxycycline against bacteria from clinical material.

Doxycycline (alpha-6-deoxy-oxytetracycline) was tested against various bacteria of recent clinical origin with 30-mug discs. The antibiotic susceptibility of these bacteria to commonly used antimicrobial agents was also established. Those bacteria which responded with equivocal zones of inhibition about the tetracycline compounds were tested by the tube dilution technique. Staphylococci and enterococci consistently displayed greater in vitro susceptibility to doxycycline than to tetracycline or demethylchlortetracycline.

Ampicillin↗

Resistance of Staphylococcus aureus to sulphamethoxazole and trimethoprim.

Strains of Staphylococcus aureus isolated from the lesions of hospital patients were surveyed for resistance to sulphamethoxazole and to trimethoprim. Of 675 strains tested, 18.5% were resistant to sulphamethoxazole and 1.6% to trimethoprim. All the trimethoprim-resistant strains were resistant to sulphamethoxazole and to a 1:20 mixture of the two drugs. Trimethoprim-resistant strains were on average more resistant to sulphamethoxazole than were trimethoprim-sensitive strains. They were all resistant to several other antimicrobial agents. Most of them had the phage-typing pattern 84/85, 84, or 85.

Anti-Bacterial Agents↗