Em49, a New Peptide Antibiotic

Meyers, Edward A.; Brown, William E.; Principe, Pacifico A.; Rathnum, Marlene L.; Parker, W.

doi:10.7164/antibiotics.26.444

Cited by 42 publications

(12 citation statements)

References 21 publications

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“…Because the octapeptins have only recently been isolated and character ized, most of the published research has been done with a mixture of octapeptins A and B designated EM 49 (9,34,61,62). Although similar structurally, the octapeptins and polymyxins differ signifi cantly in antibiotic activities.…”

Section: Native Antibioticsmentioning

confidence: 98%

Polymyxin and Related Peptide Antibiotics

Storm¹,

Rosenthal²,

Swanson³

1977

Annu. Rev. Biochem.

701

535

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The general mechanism for the antibiotic activities of the polymyxins and octapeptins has been elucidated by research using a broad range of experimental techniques. However, this phenomenon has not been described in detailed molecular terms, and this must be one of the major goals for future research in this area. Since 1947, when polymyxin was first isolated, there have been tremendous advances in our knowledge of membrane structure. The application of biophysical technology such as NMR, ESR, fluorescence spectroscopy, differential scanning calorimetry, and electron microscopy has been particularly valuable for studying model and biological membrane structures. It is these techniques which will provide a detailed molecular mechanism for the effects of these peptide antibiotics on membrane structure. In addition, the large number of antibiotic derivatives available should be exploited more extensively for structure-function correlations. The ultimate goal is to correlate the biological properties of these peptides with their effects on the physical properties of membranes and to rationalize these events in terms of lipid-peptide interactions.

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Section: Native Antibioticsmentioning

confidence: 98%

Polymyxin and Related Peptide Antibiotics

Storm¹,

Rosenthal²,

Swanson³

1977

Annu. Rev. Biochem.

701

535

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“…The length of the N -terminal fatty acyl chains also differ, with the octapeptins displaying longer C 9 or C 10 β-hydroxyl fatty acyl chains as opposed to the shorter C 7 or C 8 fatty acyl chains of polymyxins which also lack a β-hydroxyl group (polymyxin B 1 and colistin A: 6-( S )-methyloctanoyl; polymyxin B 2 and colistin B: 6-methylheptanonyl). 16–25 Notably, polymyxin B 6 is unique in that it’s the only polymyxin that has a fatty acyl chain containing a 3-hydroxy group. 15 Octapeptins and polymyxins also differ in their charges as a result of the reduced number Dab residues due to the truncated linear segment; octapeptins possess 3–4 positive charges, whereas the polymyxins possess 4–5 positive charges.…”

Section: Octapeptins and Polymyxins: Chalk And Cheese Or Peas In Amentioning

confidence: 99%

“…14 However, unlike the polymyxins which have a narrow spectrum of activity solely against Gram-negative bacteria, octapeptins exhibit a broader spectrum of activity that also includes Gram-positives, yeast, filamentous fungi and protozoa (Table 2). 16, 17, 26–31 Most importantly, octapeptins do not display cross-resistance with polymyxins against Gram-negative bacteria; this is potentially owing to a unique mode of action. Interestingly, the octapeptins generally display reduced activity against polymxyin-susceptible Gram-negative isolates.…”

Section: Antibacterial Activitymentioning

confidence: 99%

Rediscovering the octapeptins

Velkov

Roberts

2017

Nat. Prod. Rep.

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The decline in the discovery and development of novel antibiotics has resulted in the emergence of bacteria that are resistant to almost all available antibiotics. Currently, polymyxin B and E (colistin) are being used as the last-line therapy against life-threatening infections, unfortunately resistance to polymyxins in both the community and hospital setting is becoming more common. Octapeptins are structurally related non-ribosomal lipopeptide antibiotics that do not exhibit cross-resistance with polymyxins and have a broader spectrum of activity that includes Gram-positive bacteria. This makes them a precious and finite resource for the development of new antibiotics against these problematic polymyxin-resistant Gram-negative pathogens, in particular Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. This review surveys the progress in understanding octapeptin chemistry, mechanisms of antibacterial activity and biosynthesis. With the lack of cross-resistance and their broad antibacterial activity, the octapeptins represent ideal candidates for the development of a new generation of polymyxin-like lipopeptide antibiotics targeting polymyxin-resistant ‘superbugs’.

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“…This observation led to the development of a new colorimetric method for determining isoniazid with 9-chloroacridine. The reagent was shown previously to be applicable to the colorimetric analysis of primary aromatic amines and aromatic hydroxylamines (1)(2)(3)(4).…”

Section: Results a N D Discussionmentioning

confidence: 99%

“…The antibiotic has broad spectrum antibacterial activity and displays considerable antifungal and antiprotozoal activities (1)(2)(3). Proper control of the fermentation of I requires an analytical method that can monitor biosynthesis at any stage and that requires a comparatively short time.…”

mentioning

confidence: 99%

Colorimetric Determination of Peptide Antibiotics: In-Process Assay of Cyclic Octapeptidic Antibiotics in Fermentation Broths

Ivashkiv

1975

Journal of Pharmaceutical Sciences

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Em49, a New Peptide Antibiotic

Cited by 42 publications

References 21 publications

Polymyxin and Related Peptide Antibiotics

Polymyxin and Related Peptide Antibiotics

Rediscovering the octapeptins

Colorimetric Determination of Peptide Antibiotics: In-Process Assay of Cyclic Octapeptidic Antibiotics in Fermentation Broths

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