Bioassay- and metabolomics-guided screening of bioactive soil actinomycetes from the ancient city of Ihnasia, Egypt

Autoři: Mohamed Sebak aff001;  Amal E. Saafan aff002;  Sameh AbdelGhani aff003;  Walid Bakeer aff003;  Ahmed O. El-Gendy aff003;  Laia Castaño Espriu aff001;  Katherine Duncan aff001;  RuAngelie Edrada-Ebel aff001
Působiště autorů: Strathclyde Institute of Pharmacy and Biomedical Sciences, Faculty of Science, University of Strathclyde, Glasgow, Scotland, United Kingdom aff001;  Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Menoufia University, Shebin Elkom, Menoufia, Egypt aff002;  Microbiology and Immunology Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt aff003
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


Literature surveys, taxonomical differences, and bioassay results have been utilized in the discovery of new natural products to aid in Actinomycetes isolate-selection. However, no or less investigation have been done on establishing the differences in metabolomic profiles of the isolated microorganisms. The study aims to utilise bioassay- and metabolomics-guided tools that included dereplication study and multivariate analysis of the NMR and mass spectral data of microbial extracts to assist the selection of isolates for scaling-up the production of antimicrobial natural products. A total of 58 actinomycetes were isolated from different soil samples collected from Ihnasia City, Egypt and screened for their antimicrobial activities against indicator strains that included Bacillus subtilis, Escherichia coli, methicillin-resistant Staphylococcus aureus and Candida albicans. A number of 25 isolates were found to be active against B. subtilis and/or to at least one of the tested indicator strains. Principal component analyses showed chemical uniqueness for four outlying bioactive actinomycetes extracts. In addition, Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) and dereplication study led us to further select two outlying anti-MRSA active isolates MS.REE.13 and 22 for scale-up work. MS.REE.13 and 22 exhibited zones of inhibition at 19 and 13 mm against MRSA, respectively. A metabolomics-guided approach provided the steer to target the bioactive metabolites (P<0.01) present in a crude extract or fraction even at nanogram levels but it was a challenge that such low-yielding bioactive natural products would be feasible to isolate. Validated to occur only on the active side of OPLS-DA loadings plot, the isolated compounds exhibited medium to weak antibiotic activity with MIC values between 250 and 800 μM. Two new compounds, P_24306 (C10H13N2) and N_12799 (C18H32O3) with MICs of 795 and 432 μM, were afforded from the scale-up of MS.REE. 13 and 22, respectively.

Klíčová slova:

Actinobacteria – Antibiotics – Drug metabolism – Metabolites – Metabolomics – Methicillin-resistant Staphylococcus aureus – NMR spectroscopy – Streptomyces


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