Gentamicin,<sup>1</sup> a New Antibiotic Complex from Micromonospora

Weinstein, Marvin; Luedemann, George M.; Oden, Edwin M.; Wagman, G. H.; Rosselet, J. P.; Marquez, Joseph A.; Coniglio, Carmine T.; Charney, William; Herzog, Hershel L.; Black, J. J.

doi:10.1021/jm00340a034

Cited by 267 publications

(158 citation statements)

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“…AVI is produced by Streptomyces virdochromogenes strain Tü57 (4), whereas EVN was identified and isolated from the producer Micromonospora carbonacea (5,6). EVN and AVI display excellent antimicrobial activity against Gram-positive bacteria (3), including methicillin-resistant Staphylococcus aureus (7), as well as some Gram-negative bacteria, such as Borrelia burgdorferi (8).…”

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confidence: 99%

Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome

Arenz¹,

Juette

Graf³

et al. 2016

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

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The ribosome is one of the major targets for therapeutic antibiotics; however, the rise in multidrug resistance is a growing threat to the utility of our current arsenal. The orthosomycin antibiotics evernimicin (EVN) and avilamycin (AVI) target the ribosome and do not display cross-resistance with any other classes of antibiotics, suggesting that they bind to a unique site on the ribosome and may therefore represent an avenue for development of new antimicrobial agents. Here we present cryo-EM structures of EVN and AVI in complex with the Escherichia coli ribosome at 3.6- to 3.9-Å resolution. The structures reveal that EVN and AVI bind to a single site on the large subunit that is distinct from other known antibiotic binding sites on the ribosome. Both antibiotics adopt an extended conformation spanning the minor grooves of helices 89 and 91 of the 23S rRNA and interacting with arginine residues of ribosomal protein L16. This binding site overlaps with the elbow region of A-site bound tRNA. Consistent with this finding, single-molecule FRET (smFRET) experiments show that both antibiotics interfere with late steps in the accommodation process, wherein aminoacyl-tRNA enters the peptidyltransferase center of the large ribosomal subunit. These data provide a structural and mechanistic rationale for how these antibiotics inhibit the elongation phase of protein synthesis.

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mentioning

confidence: 99%

Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome

Arenz¹,

Juette

Graf³

et al. 2016

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

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“…This family produces many of the well-known antibiotics such as the aminoglycosides gentamicin and amikacin (4) . In this study, we reported the draft genome sequence of Micromonospora sp.…”

Section: Genome Annoucmentmentioning

confidence: 99%

Draft Genome Sequence of Micromonospora sp. Rc5 Isolated from desert Egyptian Soil

Amin¹

2017

jmscr

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“…The initial efforts in aminoglycoside research were directed toward discovery of potent compounds. In 1944, streptomycin was the first such agent (introduced for the treatment of tuberculosis) and it was followed by kanamycin in the 1950s, gentamicin in 1963, and tobramycin in 1968, all of which were used predominantly to treat serious infections with gram-negative bacilli (21,37,38,172). A number of factors have limited the introduction of new aminoglycosides, including their inherent potential to cause ototoxicity and nephrotoxicity.…”

Section: Discovery Of Penicillin Gmentioning

confidence: 99%

Discovery and development of new antimicrobial agents

Gootz

1990

Clin Microbiol Rev

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The unprecedented growth in the number of new antibiotics over the past two decades has been the result of extensive research efforts that have exploited the growing body of knowledge describing the interactions of antibiotics with their targets in bacterial cells. Information gained from one class of antimicrobial agents has often been used to advance the development of other classes. In the case of beta-lactams, information on structure-activity relationships gleaned from penicillins and cephalosporins was rapidly applied to the cephamycins, monobactams, penems, and carbapenems in order to discover broad-spectrum agents with markedly improved potency. These efforts have led to the introduction of many new antibiotics that demonstrate outstanding clinical efficacy and improved pharmacokinetics in humans. The current review discusses those factors that have influenced the rapid proliferation of new antimicrobial agents, including the discovery of new lead structures from natural products and the impact of bacterial resistance development in the clinical setting. The development process for a new antibiotic is discussed in detail, from the stage of early safety testing in animals through phase I, II, and III clinical trials.

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Gentamicin,¹ a New Antibiotic Complex from Micromonospora

Cited by 267 publications

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Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome

Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome

Draft Genome Sequence of Micromonospora sp. Rc5 Isolated from desert Egyptian Soil

Discovery and development of new antimicrobial agents

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Gentamicin,1 a New Antibiotic Complex from Micromonospora

Cited by 267 publications

References 0 publications

Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome

Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome

Draft Genome Sequence of Micromonospora sp. Rc5 Isolated from desert Egyptian Soil

Discovery and development of new antimicrobial agents

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Product

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Gentamicin,¹ a New Antibiotic Complex from Micromonospora