Antimicrobial properties of biosynthesized silver nanoparticles studied by flow cytometry and related techniques

This work reports the effect of silver bionanoparticles (Bio(AgNPs) synthesized by Actinobacteria CGG 11n on selected Gram (+) and Gram (–) bacteria. Flow cytometry, classical antibiogram method and fluorescent microscopy approach was used for evaluation of antimicrobial activity of Bio(AgNPs) and their combination with antibiotics. Furthermore, the performed research specified the capacity of flow cytometry method as an alternative to the standard ones and as a complementary method to electromigration techniques. The study showed antibacterial activity of both BioAgNPs and the combination of antibiotics/BioAgNPs against all the tested bacteria strains in comparison with a diffusion, dilution and bioautographic methods. The synergistic effect of antibiotics/BioAgNPs combination (e.g. kanamycin, ampicillin, neomycin and streptomycin) was found to be more notable against Pseudomonas aeruginosa representing a prototype of multi‐drug resistant “superbugs” for which effective therapeutic options are very limited.     

Chemical dereplication of marine actinomycetes by liquid chromatography–high resolution mass spectrometry profiling and statistical analysis

Discovery of novel bioactive metabolites from marine bacteria is becoming increasingly challenging, and the development of novel approaches to improve the efficiency of early steps in the microbial drug discovery process is therefore of interest. For example, current protocols for the taxonomic dereplication of microbial strains generally use molecular tools which do not take into consideration the ability of these selected bacteria to produce secondary metabolites. As the identification of novel chemical entities is one of the key elements driving drug discovery programs, this study reports a novel methodology to dereplicate microbial strains by a metabolomics approach using liquid chromatography–high resolution mass spectrometry (LC–HRMS). In order to process large and complex three dimensional LC–HRMS datasets, the reported method uses a bucketing and presence–absence standardization strategy in addition to statistical analysis tools including principal component analysis (PCA) and cluster analysis. From a closely related group of Streptomyces isolated from geographically varied environments, we demonstrated that grouping bacteria according to the chemical diversity of produced metabolites is reproducible and provides greatly improved resolution for the discrimination of microbial strains compared to current molecular dereplication techniques. Importantly, this method provides the ability to identify putative novel chemical entities as natural product discovery leads.     

Pradimicin-IRD from Amycolatopsis sp. IRD-009 and its antimicrobial and cytotoxic activities

A new polycyclic antibiotic, pradimicin-IRD, was isolated from actinobacteria Amycolatopsis sp. IRD-009 recovered from soil of Brazilian rainforest undergoing restoration area. This molecule is the major compound produced in solid culture media. The new compound was detected by a focused method of precursor ion (high-performance liquid chromatography coupled to tandem mass spectrometer) developed previously to identify unusual aminoglycosyl sugar moieties. The compound was isolated and its structure was, therefore, elucidated by high-resolution mass spectrometry, and 1D and 2D nuclear magnetic resonance experiments. Pradimicin-IRD displayed potential antimicrobial activity against Streptococcus agalactiae (MIC 3.1 μg/mL), Pseudomonas aeruginosa (MIC 3.1 μg/mL) and Staphylococcus aureus (MIC 3.1 μg/mL), and also cytotoxicity against tumour and non-tumour cell lines with IC₅₀ values ranging from 0.8 μM in HCT-116 colon carcinoma cells to 2.7 μM in MM 200 melanoma cells. Particularly, these biological properties are described for the first time for this chemical class.     

Persicamidines—Unprecedented Sesquarterpenoids with Potent Antiviral Bioactivity against Coronaviruses

A new family of highly unusual sesquarterpenoids (persicamidines A–E) exhibiting significant antiviral activity was isolated from a newly discovered actinobacterial strain, Kibdelosporangium persicum sp. nov., collected from a hot desert in Iran. Extensive NMR analysis unraveled a hexacyclic terpenoid molecule with a modified sugar moiety on one side and a highly unusual isourea moiety fused to the terpenoid structure. The structures of the five analogues differed only in the aminoalkyl side chain attached to the isourea moiety. Persicamidines A–E showed potent activity against hCoV-229E and SARS-CoV-2 viruses in the nanomolar range together with very good selectivity indices, making persicamidines promising as starting points for drug development.