Effects of the antibiotic resistomycin on the synthesis of macromolecules

Haupt, Ina; Wähnert, U.; Pitra, C.; Löber, G.; Luck, G.; Eckardt, K.

doi:10.1002/jobm.3630150604

Cited by 12 publications

(5 citation statements)

References 17 publications

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“…Borrelidin and resistomycin are commercially highly relevant natural products. Borrelidin is a nitrile-containing macrolide that acts as a potent inhibitor of both bacterial and eukaryotic threonyl-tRNA synthetases (Habibi et al , 2012; Nass & Hasenbank, 1970), whilst resistomycin is a pentacyclic polyketide metabolite that inhibits RNA polymerase (Haupt et al , 1975), HIV-1 protease (Roggo et al , 1994) and apoptosis (Shiono et al , 2002), and was first applied as drug for the treatment of tuberculosis. 1-Carbomethoxy-phenazine is known to have weaker antimicrobial activity.…”

Section: Discussionmentioning

confidence: 99%

Eliciting antibiotics active against the ESKAPE pathogens in a collection of actinomycetes isolated from mountain soils

et al. 2014

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The rapid emergence of multidrug-resistant (MDR) bacterial pathogens poses a major threat for human health. In recent years, genome sequencing has unveiled many poorly expressed antibiotic clusters in actinomycetes. Here, we report a well-defined ecological collection of >800 actinomycetes obtained from sites in the Himalaya and Qinling mountains, and we used these in a concept study to see how efficiently antibiotics can be elicited against MDR pathogens isolated recently from the clinic. Using 40 different growth conditions, 96 actinomycetes were identified – predominantly Streptomyces – that produced antibiotics with efficacy against the MDR clinical isolates referred to as ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and/or Enterobacter cloacae. Antimicrobial activities that fluctuated strongly with growth conditions were correlated with specific compounds, including borrelidin, resistomycin, carbomethoxy-phenazine, and 6,7,8- and 5,6,8-trimethoxy-3-methylisocoumarin, of which the latter was not described previously. Our work provided insights into the potential of actinomycetes as producers of drugs with efficacy against clinical isolates that have emerged recently and also underlined the importance of targeting a specific pathogen.

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Section: Discussionmentioning

confidence: 99%

Eliciting antibiotics active against the ESKAPE pathogens in a collection of actinomycetes isolated from mountain soils

et al. 2014

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“…inhibition of HIV-1 protease, 60 as well as RNA and DNA polymerase, and activity against Gram-positive bacteria and mycobacteria. 61 More recently, it has also been implicated as a modulator of apoptosis, and may thus serve as a valuable tool in cell biology. 62 The structurally fascinating b-rubromycin 63 and griseorhodin A, 64 as well as fredericamycin 65 (Fig.…”

Section: Christian Hertweck Andriy Luzhetskyy Yuri Rebetsmentioning

confidence: 99%

Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork

et al. 2007

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“…This was confirmed after comparison of HRMS, UV, and t R data with a purchased standard (Figures S1 and S2). Resistomycin is a compound that is reported to possess potent cytotoxicity and is a weak, broad-spectrum antibiotic , that inhibits DNA-dependent RNA polymerase. − …”

Section: Results and Discussionmentioning

confidence: 99%

Phylum-Specific Regulation of Resistomycin Production in a Streptomyces sp. via Microbial Coculture

et al. 2014

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Actinomycete genomes are encoded with immense potential to produce secondary metabolites, however standard laboratory culture experiments rarely provide the conditions under which associated biosynthetic pathways are expressed. Despite years of research attempting to access these pathways and aside from a few well-studied bacterial quorum sensing systems, little is known about the specificity of secondary metabolite regulation in bacteria, such as the conditions under which a bacterium produces an antibiotic and the extent to which it does so in recognition of a particular species in the immediate environment. In the current study, we observed that the cocultivation of a Streptomyces sp. (strain B033) with four pathogenic strains of the phylum Proteobacteria resulted in the production of the antibiotic resistomycin. After further coculture experiments, we determined that Proteobacteria induced the production of resistomycin in B033 at significantly higher rates (65%) than strains from the phyla Firmicutes (5.9%) and Actinobacteria (9.1%), supporting that the regulation of secondary metabolism in bacteria can be dependent on the species present in the immediate environment. These results suggest a lack of promiscuity of antibiotic biosynthetic pathway regulation and indicate that it is feasible to mine existing microbial strain libraries for antibiotics in a phylum-specific manner.

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Effects of the antibiotic resistomycin on the synthesis of macromolecules

Cited by 12 publications

References 17 publications

Eliciting antibiotics active against the ESKAPE pathogens in a collection of actinomycetes isolated from mountain soils

Eliciting antibiotics active against the ESKAPE pathogens in a collection of actinomycetes isolated from mountain soils

Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork

Phylum-Specific Regulation of Resistomycin Production in a Streptomyces sp. via Microbial Coculture

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