title: Cytotoxic and antibacterial substances against multi-drug resistant pathogens from marine sponge symbiont: Citrinin, a secondary metabolite of Penicillium sp.
abstract: OBJECTIVE
  To Isolate, purify, characterize, and evaluate the bioactive compounds from the sponge-derived fungus Penicillium sp. FF001 and to elucidate its structure.
  
  
  METHODS
  The fungal strain FF001 with an interesting bioactivity profile was isolated from a marine Fijian sponge Melophlus sp. Based on conidiophores aggregation, conidia development and mycelia morphological characteristics, the isolate FF001 was classically identified as a Penicillium sp. The bioactive compound was identified using various spectral analysis of UV, high resolution electrospray ionization mass spectra, 1H and 13C NMR spectral data. Further minimum inhibitory concentrations (MICs) assay and brine shrimp cytotoxicity assay were also carried out to evaluate the biological properties of the purified compound.
  
  
  RESULTS
  Bioassay guided fractionation of the EtOAc extract of a static culture of this Penicillium sp. by different chromatographic methods led the isolation of an antibacterial, anticryptococcal and cytotoxic active compound, which was identified as citrinin (1). Further, citrinin (1) is reported for its potent antibacterial activity against methicillin-resistant Staphylococcus aureus (S. aureus), rifampicin-resistant S. aureus, wild type S. aureus and vancomycin-resistant Enterococcus faecium showed MICs of 3.90, 0.97, 1.95 and 7.81 µg/mL, respectively. Further citrinin (1) displayed significant activity against the pathogenic yeast Cryptococcus neoformans (MIC 3.90 µg/mL), and exhibited cytotoxicity against brine shrimp larvae LD50 of 96 µg/mL.
  
  
  CONCLUSIONS
  Citrinin (1) is reported from sponge associated Penicillium sp. from this study and for its strong antibacterial activity against multi-drug resistant human pathogens including cytotoxicity against brine shrimp larvae, which indicated that sponge associated Penicillium spp. are promising sources of natural bioactive metabolites.
authors.affiliation: Centre for Drug Discovery and Conservation, Institute of Applied Sciences, The University of the South Pacific, Laucala Campus, Suva, Fiji Islands.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Subramani
authors.forename: Rohitesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Pritesh
authors.initials: P
authors.lastname: Prasad
authors.forename: William
authors.initials: W
authors.lastname: Aalbersberg
authors.forename: S T
authors.initials: ST
authors.lastname: Retheesh
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001156:Artemia / Q000187:drug effects; D002953:Citrinin / Q000737:chemistry / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D007928:Lethal Dose 50; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010407:Penicillium / Q000737:chemistry* / Q000166:cytology; D011161:Porifera / Q000382:microbiology*; D018675:Toxicity Tests
chemical_list: D000900:Anti-Bacterial Agents; D002953:Citrinin
keywords: Antimicrobial; Citrinin; Cytotoxic activity; Multi-drug resistant; Penicillium sp.; Sponge derived