title: 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 IC50values 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.
authors.affiliation: Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India.|Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India.
authors.forename: Palak
authors.initials: P
authors.lastname: Arora
authors.affiliation: Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India.|Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India.
authors.forename: Zahoor A
authors.initials: ZA
authors.lastname: Wani
authors.affiliation: Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India.|Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India.
authors.forename: Yedukondalu
authors.initials: Y
authors.lastname: Nalli
authors.affiliation: Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India. asifali@iiim.ac.in.|Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India. asifali@iiim.ac.in.
authors.forename: Asif
authors.initials: A
authors.lastname: Ali
authors.affiliation: Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India. srhassan@iiim.ac.in.|Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India. srhassan@iiim.ac.in.
authors.forename: Syed
authors.initials: S
authors.lastname: Riyaz-Ul-Hassan
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D002939:Ciprofloxacin / Q000494:pharmacology; D004338:Drug Combinations; D060026:Endophytes / Q000378:metabolism*; D006035:Glycyrrhiza / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D060888:Real-Time Polymerase Chain Reaction; D004718:Saccharomycetales / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000254:growth & development*; D013297:Streptococcus pyogenes / Q000254:growth & development*; D013307:Streptomycin / Q000494:pharmacology; D024341:Xanthophylls / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D024341:Xanthophylls; D002939:Ciprofloxacin; C031841:staphyloxanthin; D000667:Ampicillin; D013307:Streptomycin
keywords: Antimicrobial activity; Biofilm disruption; Endophyte; Fungal secondary metabolite; Glycyrrhiza; Licorice; Phoma