Ketolides are a new subgroup of macrolide antibiotics designed to overcome bacterial resistance to macrolides. The ketolides are semi-synthetic derivatives. Currently, the only ketolide on the U.S. market is telithromycin sold under the brand name Ketek®.
Macrolides inhibit RNA-dependent protein synthesis by reversibly binding to the 50S ribosomal subunits of susceptible microorganisms. They induce dissociation of peptidyl transfer RNA (tRNA) from the ribosome during the elongation phase. Thus, RNA-dependent protein synthesis is suppressed, and bacterial growth is inhibited.
The first macrolide antibiotic, erythromycin, was isolated in 1952 from products produced by . In 1991, two semisynthetic derivatives of erythromycin, azithromycin and clarithromycin, were brought to market. Roxithromycin was first introduced by German pharmaceutical company Hoechst Uclaf in 1987, however, it is not available in U.S.
Roxithromycin is a semi-synthetic 14-membered ring macrolide antibiotic in which the erythronolide A lactone ring has been modified to prevent inactivation by gastric acid.
Antibiotics like sulfonamides and trimethorim interfere with folate metabolism by blocking enzymes required for the synthesis of tetrahydrofolate; an enzyme needed by bacterial cells for the synthesis of folic acid production of DNA and RNA and amino acids.
Streptomyces genera carry an extremely versatile group of biosynthetic machineries capable to produce complex molecules of medical, agricultural and economical significance. They are recognized as the most resourceful producers of molecules that present antibiotic activities. The mutualism existing among several actinobacteria and plants, ants and other organisms also seemed to be a key element to the capability to produce such small molecules.,
The actinobacteria Streptomyces wadayamensis A23, an endophitic strain, was recently sequenced and previous work showed qualitatively that the strain inhibits the growth of some pathogens. Herein we report the genome analysis of S. wadayamensis which reveals several antibiotic biosynthetic pathways. Using mass spectrometry, we were able to identify desferoxamines, several antimycins and candicidin, as predicted. Additionally, it was possible to confirm that the biosynthetic machinery of the strain when compared to identified known metabolites is far underestimated. As suggested by biochemical qualitative tests, genome encoded information reveals that the strain A23 has high capability to produce antibiotics.
Driven by the current status of the genome to natural products programs we invested in the Whole Genome Shotgun project of Streptomyces wadayamensis A23, an endophytic strain isolated from Citrus reticulata (tangerine). Biochemical qualitative tests showed that strain A23 inhibits the growth of Candida albicans pathogen, Bacillus megaterium, Neisseria meningitides strains, and multiresistant Staphylococcus aureus. Herein we report our preliminary results generated after genome annotation and mining of the WGS project. Annotation was critical to predict that S. wadayamensis has high capability to biosynthesize antibiotics. Experimental evaluation combined to powerful analytical tools revealed the production of several bioactive metabolites as anticipated by mining.
The input of the genome data into the antibiotics & Secondary Metabolite Analysis SHell (antiSMASH) server (version 3.0.5) resulted in an output predicting the presence of 32 gene clusters codifying for secondary metabolites biosynthesis. Biosynthetic systems as terpene, nrps, bacteriocin-terpene, t1-pks, t3-pks, bacteriocin, nrps-t1pks, tiopeptide-lantipeptide, lantipeptide-nrps-t1-pks, siderophore, ectoine, lassopeptide, lantipeptide and other clusters are apparently encoded in S. wadayamensis genome (). Crossing the output results from antiSMASH within the MIBiG (Minimum Information about a Biosynthetic Gene cluster) pipeline, it was possible to predict more accurately certain metabolites and/or the most likely class that the gene cluster fits as presented in .
With advances in organic chemistry many antibiotics are now also obtained by chemical synthesis, such as the sulfa drugs. Drugs used in the chemotherapy of infectious diseases are classified into two groups. Drugs that have been synthesized by chemical procedures in the laboratory are called synthetic drugs while those produced by bacteria and fungi are called antibiotics 2.
Schallmey 21, isolated soil bacteria which shows antibiotic activity under normal growth condition and was found inhibiting some gram positive and some gram negative organism both Bacillus lentus and Bacillus alvei also shows antibacterial activity against Staphylococcus aureus. Bacillus pumillus only show slight zone of inhibition on Proteus spp while it is inactive against others.