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

Abstract

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.

Bioprospecting for culturable actinobacteria with antimicrobial properties isolated from rivers in Colombian Orinoquia

“…Of all isolates obtained (374 actinobacteria isolates), a large number of them were active against Bacillus subtilis, consistent with previous studies, [18] and against A. baumannii and K. pneumonia which are two carbapemen-resistant microorganisms that have become problematic due to the absence of effective medication [19]. Four strains isolated in this study showed inhibition of A. baumannii, with two of them being able to inhibit K. pneumoniae.…”

Metabolomics-Driven Discovery of a Prenylated Isatin Antibiotic Produced byStreptomycesSpecies MBT28

“…Conversely, 1 H NMR spectra of MBT28-91 specifically exhibited resonances for 4-hydroxybenzoic acid and an unknown compound with typical resonances at δ 7.03 (t, J = 7.2 Hz), which were absent in the other two strains. The known antimicrobial compound borrelidin (δ 6.60, 6.90, and 6.31), which was previously shown to be produced by MBT28, 22 was detected in all samples, but its production level was 10% lower in MBT28-91 as compared to the parent or mutant MBT28-30. This strongly suggests that borrelidin was not the causative agent of the increased bioactivity.…”

Identification of novel endophenaside antibiotics produced by Kitasatospora sp. MBT66

“…MBT66 that was shown to be a prolific producer of antibiotics with activity against Gram-positive and Gramnegative pathogens. 16 Preliminary analysis predicted that it produced a number of compounds exhibiting similar chemical properties (TLC and HPLC-UV detection) to 1-carbomethoxy phenazine that was described in another actinomycete Streptomyces sp. MBT70.…”

“…MBT70. 16 The phenazines are a group of heterocyclic, nitrogen-containing compounds isolated primarily from Pseudomonas and Streptomyces bacteria. 17 They differ in chemical and physical properties according to the nature and/or position of functionalities, and thus give rise to a full spectrum of colors ranging from the deep red to the light blue.…”