Antimicrobial Potential of Thiodiketopiperazine Derivatives Produced by Phoma sp., an Endophyte of Glycyrrhiza glabra Linn.

Abstract

During the screening of endophytes obtained from Glycyrrhiza glabra Linn., the extract from a fungal culture designated as GG1F1 showed significant antimicrobial activity. The fungus was identified as a species of the genus Phoma and was most closely related to Phoma cucurbitacearum. The chemical investigation of the GG1F1 extract led to the isolation and characterization of two thiodiketopiperazine derivatives. Both the compounds inhibited the growth of several bacterial pathogens especially that of Staphylococcus aureus and Streptococcus pyogenes, with IC values of less than 10 μM. The compounds strongly inhibited biofilm formation in both the pathogens. In vitro time kill kinetics showed efficient bactericidal activity of these compounds. The compounds were found to act synergistically with streptomycin while producing varying effects in combination with ciprofloxacin and ampicillin. The compounds inhibited bacterial transcription/translation in vitro, and also inhibited staphyloxanthin production in S. aureus. Although similar in structure, they differed significantly in some of their properties, particularly the effect on the expression of pathogenecity related genes in S. aureus at sub-lethal concentrations. Keeping in view the antimicrobial potential of these compounds, it would be needful to scale up the production of these compounds through fermentation technology and further explore their potential as antibiotics using in vivo models.

Interactions of 172 plant extracts with human organic anion transporter 1 (SLC22A6) and 3 (SLC22A8): a study on herb-drug interactions

“…Echium russicum is a rare plant growing in central and southeastern Europe, and has shown antioxidant and antimicrobial activities (Niciforovic et al, 2010). Glycyrrhiza glabra is the source of licorice which has been widely used in tobacco and food industry (Arora et al, 2016). Juncus effusus is a well-known traditional Chinese medicine used as a sedative, anxiolytic and antipyretic to treat fidgetiness and insomnia (Ma et al, 2015).…”

Antibacterial potential of Juglomycin A isolated fromStreptomyces achromogenes, an endophyte ofCrocus sativusLinn

“…Each well was inoculated with 10 4 cells of the relevant test organism and incubated at 37°C for 24 h. Each plate had a set of controls as well: a column with a broad‐spectrum antibiotic (ciprofloxacin/nystatin) as positive controls, a column without the test compound, and one without the relevant test organism. Absorbance was measured spectrophotometrically at 630 nm, IC 50 of the extracts was calculated from the average percent inhibition of three replicates of each concentration as described previously (Arora et al ) and MIC of the compounds was calculated according to the Clinical and Laboratory Standards Institute ( (CLSI) guidelines. Nystatin was obtained from Sigma‐Aldrich.…”

“…Tubes containing MHB with the compound at different concentrations (1× MIC and 2× MIC) were inoculated with the test organism to a density of 10 8 cells per ml and incubated at 37°C for 48 h. Viability counts were checked at time 0, 2, 4, 8, 10, 24 and 48 h by serially diluting in NSS and plating on MHA media. The percentage reduction and log 10 reduction from the initial microbial count for each time interval were calculated according to a previously described method (Arora et al ). Two independent experiments were conducted and the mean data were plotted.…”

Symbiosis-inspired approaches to antibiotic discovery

“…LG23 normally associated with the Chinese medicinal plant Mahonia fortunea ; the title NP was found to be potent against both Gram-positive and negative bacteria and proved especially effective against the pathogens S. pyrogenes , P. aeruginosa and S. aureus , 110 ii) recent reports by Hertweck and co-workers that the orchid root-associated symbiont Daldinia eschscholtzii (a fungus) produces a wide assortment of aromatic PKS-derived NPs inclusive of naphthalene-based daldionins, nodulones B and C and eight other previously known species capable of exerting antibacterial activities against VRE, MRSA and the pathogenic fungus P. notatum , 111 iii) recent efforts by Wani and co-workers during which an endophytic fungus, Phoma sp., (closely related to P. cucurbitacearum ) associated with the Glycyrrhiza glabra Linn., a well-known medicinal plant, was found to generate two thiodiketopiperazine (thio-DKP) derivatives with the ability to significantly inhibit pathogenic bacteria such as S. aureus and S. pyogenes . 112 Both DKPs were shown to impair biofilm formation in both pathogens and acted synergistically with streptomycin while producing various effects in tandem with the established antimicrobials ciprofloxacin and ampicillin, 112 iv) the recent application of a metagenomics approach based on pulsed-field gel electrophoresis (PFGE) enabling the correlation of endophyte-associated small peptides from the medicinal black crowberry plant ( Empetrum nigrum L.) to antibacterial activities against E. coli and/or S. aeureus . The applied approach enabled identification of a fungally-generated protein EN-AP1 whose proteolytic processing (by the E. coli metagenomic host) afforded a number of small peptides with antibacterial activity (7 out of 12); bioactivities and peptide structures were elucidated using a combination of peptide synthesis, digestions and in silico analyses.…”