Erratum: A new antibiotic kills pathogens without detectable resistance

Ling, Losee L; Schneider, Tanja; Peoples, Aaron J.; Spoering, Amy L.; Engels, Ina; Conlon, Brian P.; Mueller, Anna; Schäberle, Till F.; Hughes, Dallas E.; Epstein, Slava S.; Jones, Michael A.; Lazarides, Linos; Steadman, Victoria A.; Cohen, Douglas R.; Felix, Cintia R.; Fetterman, K. Ashley; Millett, William P.; Nitti, Anthony; Zullo, Ashley; Chen, Chao; Lewis, Kim

doi:10.1038/nature14303

Cited by 42 publications

(37 citation statements)

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“…NovoBiotic Pharmaceuticals (Cambridge, MA, USA) is using an 'iChip' to culture and isolate bacteria in situ in soil, which led to the highly publicized discovery of teixobactin. 310 Sanofi has partnered with the Fraunhofer Institute for Molecular Biology and Applied Ecology (Aachen, Germany) in a joint effort to explore natural products, mining Sanofi's collection of 4100 000 different microorganisms to cultivate them under various conditions and stimulate them to produce active substances. 311 The Community for Open Antimicrobial Drug Discovery (Brisbane, Australia) is a Wellcome Trust and the University of Queensland initiative that is attempting to mine the chemical diversity contained in millions of organic chemist's laboratories around the world to uncover new synthetic chemotypes.…”

Section: Conclusion and Future Outlookmentioning

confidence: 99%

Antibiotics in the clinical pipeline at the end of 2015

2016

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There is growing global recognition that the continued emergence of multidrug-resistant bacteria poses a serious threat to human health. Action plans released by the World Health Organization and governments of the UK and USA in particular recognize that discovering new antibiotics, particularly those with new modes of action, is one essential element required to avert future catastrophic pandemics. This review lists the 30 antibiotics and two β-lactamase/β-lactam combinations first launched since 2000, and analyzes in depth seven new antibiotics and two new β-lactam/β-lactamase inhibitor combinations launched since 2013. The development status, mode of action, spectra of activity and genesis (natural product, natural product-derived, synthetic or protein/mammalian peptide) of the 37 compounds and six β-lactamase/β-lactam combinations being evaluated in clinical trials between 2013 and 2015 are discussed. Compounds discontinued from clinical development since 2013 and new antibacterial pharmacophores are also reviewed.

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Section: Conclusion and Future Outlookmentioning

confidence: 99%

Antibiotics in the clinical pipeline at the end of 2015

2016

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“…12 Regarding compounds 3 and 4, it must be considered that one double bond in the hydrophobic polyene region in both compounds is replaced by an epoxy group. It is possible that the epoxy group causes steric hindrance, interfering with the polyene macrolide-sterol Table 1 1 H (600 MHz, CD 3 OD) and 13 C NMR (150 MHz, CD 3 OD) spectra data of 2-4 (δ in p.p.m., J in Hz) 2 3 4…”

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confidence: 99%

Three novel polyene macrolides isolated from cultures of Streptomyces lavenduligriseus

Yang

et al. 2015

J Antibiot

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Actinomycetes have evolved in the process of ecological interactions between animals, plants and microorganisms in the environment to produce new classes of secondary metabolites with novel structures, 1-3 of which polyene macrolides are very interesting bioactive compounds with a wide range of biological activities and subject to a relatively low incidence of resistance. 4,5 Many of these molecules have been successfully isolated and turned into useful drugs and other organic chemicals. In our study aimed at the discovering of novel antifungals, the soil actinomycete, Streptomyces lavenduligriseus, was found to produce strong antifungal components. Bioactivity-guided isolation and purification yielded filipin III 1 and three novel polyene macrolides, compound 2, 3 and 4 ( Figure 1). Details of the isolation, structure elucidation and the antifungal activities of these compounds are presented below.The strain of S. lavenduligriseus was cultivated in 250-ml Erlenmeyer flasks containing 30 ml of seed medium (2% glucose, 3% soybean meal, 2% soluble starch, 2% glycerol, 0.02% MgSO 4 ·7H 2 O and 0.02% KH 2 PO 4 , pH 7.5). The flasks were shaken at 220 r.p.m. on a rotary shaker at 28°C for 2 days. The seed culture (8%) was transferred into 500-ml Erlenmeyer flasks containing 50 ml of production medium (4% cornstarch, 0.8% glucose, 2.2% soybean meal, 0.1% MgSO 4 ·7H 2 O, 0.02% KH 2 PO 4 and 0.2% NaCl). The flasks were incubated at 220 r.p.m. on a rotary shaker at 28°C for 7 days. The cells were lysed with EtOH, which was then removed by concentration in vacuo. The resulting aqueous concentrate was partitioned successively with EtOAc (3 × 3 l) and BuOH (3 × 3 l). The combined extracts were concentrated under reduced pressure to yield 68 g of brown gum. This material was subjected to silica gel chromatography using a gradient mixture of CHCl 3 -MeOH (from 100:0 to 0:100), yielding nine fractions (A-I). A fraction (5.65 g) was identified as containing polyene macrolides by assaying for bioactivity against Candida albicans and by a diode array detector (DAD)/UV spectra with three characteristic λ max at 289, 303, 319 nm. 6 The fraction was further fractionated by successive preparative HPLC (YMC-Pack RP-C18 (YMC, Tokyo, Japan), 30 × 250 mm 2 , 35% MeCN in H 2 O, 10 mlmin − 1 ), yielding fractions 1-8. Fraction 3 (26.5 mg) was further purified by semi-prep RP-HPLC (YMC-Pack RP-C18, 20 × 250 mm 2 , 35% MeCN in H 2 O, 7 ml min − 1 ) to attain compound 4 (23.6 mg; t R = 20.1 min). Using the same procedure, purification of fraction 6 (56.5 mg) yielded compounds 3 (8.3 mg; t R = 72.6 min) and 2 (7.3 mg; t R = 81.2 min), fraction 8 (69.5 mg) afforded compound 1 (12.6 mg; t R = 63.5 min).Compound 1 was identified as filipin III by comparing its NMR and MS data with those previously reported. 7 The molecular formula of compound 2 was determined to be C 38 H 64 O 13 (seven degrees of unsaturation) on the basis of its positive HR-ESI-MS at the m/z value = 751.4226 [M+Na] + , 74 a.m.u. higher than that of compound 1, in agreement with ...

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“…Below we discuss structural studies on a selection of representative peptides that bind lipid II, including plectasin, teixobactin, tridecaptin A1, and nisin . These peptides were chosen either because of their unique modes of action or because of their popularity.…”

Section: Peptide Antibiotics That Bind Lipid IImentioning

confidence: 99%

Towards the Native Binding Modes of Antibiotics that Target Lipid II

et al. 2019

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The alarming rise of antimicrobial resistance (AMR) imposes severe burdens on healthcare systems and the economy worldwide, urgently calling for the development of new antibiotics. Antimicrobial peptides could be ideal templates for next‐generation antibiotics, due to their low propensity to cause resistance. An especially promising branch of antimicrobial peptides target lipid II, the precursor of the bacterial peptidoglycan network. To develop these peptides into clinically applicable compounds, detailed information on their pharmacologically relevant modes of action is of critical importance. Here we review the binding modes of a selection of peptides that target lipid II and highlight shortcomings in our molecular understanding that, at least partly, relate to the widespread use of artificial membrane mimics for structural studies of membrane‐active antibiotics. In particular, with the example of the antimicrobial peptide nisin, we showcase how the native cellular membrane environment can be critical for understanding of the physiologically relevant binding mode.

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Erratum: A new antibiotic kills pathogens without detectable resistance

Cited by 42 publications

References 1 publication

Antibiotics in the clinical pipeline at the end of 2015

Antibiotics in the clinical pipeline at the end of 2015

Three novel polyene macrolides isolated from cultures of Streptomyces lavenduligriseus

Towards the Native Binding Modes of Antibiotics that Target Lipid II

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