Tissue residues and metabolism of avilamycin in swine and rats

Magnussen, J. D.; Dalidowicz, John E.; Thomson, Thomas D.; Donoho, Alvin L.

doi:10.1021/jf00002a018

Cited by 22 publications

(9 citation statements)

References 2 publications

(2 reference statements)

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“…Avi is extensively metabolized in rats and pigs (56), at the orthoester C16 link. This unique feature of the orthosomycin family, and the Cl reduced derivatives, place this antibiotic family at the front line of antibiotics with reduced environmental hazards.…”

Section: Avi and Evn Resistance Mechanismsmentioning

confidence: 99%

Avilamycin and evernimicin induce structural changes in rProteins uL16 and CTC that enhance the inhibition of A-site tRNA binding

Krupkin

Wekselman

Matzov

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Two structurally unique ribosomal antibiotics belonging to the orthosomycin family, avilamycin and evernimicin, possess activity against Enterococci, Staphylococci, and Streptococci, and other Gram-positive bacteria. Here, we describe the high-resolution crystal structures of the eubacterial large ribosomal subunit in complex with them. Their extended binding sites span the A-tRNA entrance corridor, thus inhibiting protein biosynthesis by blocking the binding site of the A-tRNA elbow, a mechanism not shared with other known antibiotics. Along with using the ribosomal components that bind and discriminate the A-tRNA-namely, ribosomal RNA (rRNA) helices H89, H91, and ribosomal proteins (rProtein) uL16-these structures revealed novel interactions with domain 2 of the CTC protein, a feature typical to various Gram-positive bacteria. Furthermore, analysis of these structures explained how single nucleotide mutations and methylations in helices H89 and H91 confer resistance to orthosomycins and revealed the sequence variations in 23S rRNA nucleotides alongside the difference in the lengths of the eukaryotic and prokaryotic α1 helix of protein uL16 that play a key role in the selectivity of those drugs. The accurate interpretation of the crystal structures that could be performed beyond that recently reported in cryo-EM models provide structural insights that may be useful for the design of novel pathogen-specific antibiotics, and for improving the potency of orthosomycins. Because both drugs are extensively metabolized in vivo, their environmental toxicity is very low, thus placing them at the frontline of drugs with reduced ecological hazards. degradable antibiotics | ribosomes | resistance | species-specific antibiotics | Gram-positive

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Section: Avi and Evn Resistance Mechanismsmentioning

confidence: 99%

Avilamycin and evernimicin induce structural changes in rProteins uL16 and CTC that enhance the inhibition of A-site tRNA binding

Krupkin

Wekselman

Matzov

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Avilamycin administered orally at 60 ppm is excreted almost exclusively in the feces, and only very small residues are found in the tissues of swine and rats (148). Everninomycin can be administered only by intravenous injection (163).…”

Section: Avilamycinmentioning

confidence: 99%

Antimicrobial Growth Promoters Used in Animal Feed: Effects of Less Well Known Antibiotics on Gram-Positive Bacteria

2003

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There are not many data available on antibiotics used solely in animals and almost exclusively for growth promotion. These products include bambermycin, avilamycin, efrotomycin, and the ionophore antibiotics (monensin, salinomycin, narasin, and lasalocid). Information is also scarce for bacitracin used only marginally in human and veterinary medicine and for streptogramin antibiotics. The mechanisms of action of and resistance mechanisms against these antibiotics are described. Special emphasis is given to the prevalence of resistance among gram-positive bacteria isolated from animals and humans. Since no susceptibility breakpoints are available for most of the antibiotics discussed, an alternative approach to the interpretation of MICs is presented. Also, some pharmacokinetic data and information on the influence of these products on the intestinal flora are presented

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“…2,3 It was perhaps not understood that the method reported by Formica and Giannone is not specific for unchanged avilamycin, but rather measures the total of avilamycin and any metabolites that include the dichloroisoeverninic acid moiety. The second report by Magnussen et al used carbon-14-labeled avilamycin to show that in fact very little avilamycin remains in the feces and that extensive metabolism has occurred.…”

Section: Avilamycin Is Poorly Absorbed Is Extensively Metabolized Bymentioning

confidence: 99%

Avilamycin is poorly absorbed, is extensively metabolized by swine and is not persistent in the environment

Burnett

2005

J. Mass Spectrom.

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Tissue residues and metabolism of avilamycin in swine and rats

Cited by 22 publications

References 2 publications

Avilamycin and evernimicin induce structural changes in rProteins uL16 and CTC that enhance the inhibition of A-site tRNA binding

Avilamycin and evernimicin induce structural changes in rProteins uL16 and CTC that enhance the inhibition of A-site tRNA binding

Antimicrobial Growth Promoters Used in Animal Feed: Effects of Less Well Known Antibiotics on Gram-Positive Bacteria

Avilamycin is poorly absorbed, is extensively metabolized by swine and is not persistent in the environment

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