Furanone derivative and sesquiterpene from Antarctic marine-derived fungus Penicillium sp. S-1-18.

A new furanone derivative, butanolide A (1), and a new sesquiterpene, guignarderemophilane F (2), together with six known compounds, were isolated from the fungus Penicillium sp. S-1-18 derived from Antarctic marine. The new structures were determined by spectroscopic studies such as 1D- and 2D-NMR and MS analyses. The absolute configuration of 1 was determined by the modified Mosher's method, while the absolute configuration of 2 was determined by calculated ECD spectroscopy. The isolated secondary metabolites were evaluated for their protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Compound 1 showed moderate inhibitory activity against PTP1B with IC50 value of 27.4 µM.

Streptomyces sp. AT37 isolated from a Saharan soil produces a furanone derivative active against multidrug-resistant Staphylococcus aureus.

A novel actinobacterium strain, named AT37, showed a strong activity against some multidrug-resistant Staphylococcus aureus, including methicillin-resistant S. aureus MRSA ATCC 43300, other clinical isolates of MRSA and vancomycin resistant S. aureus VRSA S1. The strain AT37 was isolated from a Saharan soil by a dilution agar plating method using chitin-vitamin agar medium supplemented with rifampicin. The morphological and chemical studies indicated that this strain belonged to the genus Streptomyces. Its 16S rRNA gene sequence was determined and a database search indicated that it was closely associated with the type strain of Streptomyces novaecaesareae NBRC 13368T with 99.6% of similarity. However, the comparison of the morphological and the physiological characteristics of the strain with those of the nearest species showed significant differences. The strain AT37 secreted the antibiotic optimally during mid-stationary phase of growth. One active compound (AT37-1) was extracted from the culture broth with dichloromethane, separated on silica gel plates and purified by HPLC. Based on spectroscopic analysis of UV-Visible, infrared, and 1H and 13C NMR spectra and spectrometric analysis, the chemical structure of the compound AT37-1 was identified as 5-[(5E,7E,11E)-2,10-dihydroxy-9,11-dimethyl-5,7,11-tridecatrien-1-yl]-2-hydroxy-2-(1-hydroxyethyl)-4-methyl-3(2H)-furanone. Minimum inhibitory concentrations and minimum biofilm inhibitory concentration (MBIC50) of this compound showed significant activity against multidrug-resistant S. aureus with 15-30 and 10-15 µg/mL, respectively.

Sodium ascorbate as a quorum sensing inhibitor of Pseudomonas aeruginosa.

AIMS: Quorum sensing circuits regulate virulence factors in Pseudomonas aeruginosa and coordinate bacterial pathogenicity. We are interested in exploring available medications for their antiquorum sensing activity. METHODS AND RESULTS: First, we determined the MIC of ascorbate against Ps. aeruginosa strain PAO1, and all further experiments used concentrations below the MIC so that results could not be caused by reduced viability. Tests of subinhibitory concentrations of sodium ascorbate on cell signals were performed using a reporter strain assay. Sub-MICs of sodium ascorbate resulted in significant reduction of the signalling molecules C4-HSL and 3-oxo-C12-HSL (P < 0·01). The influence of sub-MIC of sodium ascorbate on virulence factors was also determined and ascorbate treatment led to significant depression of elastase, protease and haemolysin activities. In addition, inhibition of pyocyanin production, attenuation of biofilm formation and alteration of Pseudomonas motility was observed. Analysis by RT-PCR tested the effect of ascorbate on the expression of QS regulatory genes. Expression of QS regulatory genes, lasI, lasR, rhlI, rhlR, pqsR and pqsA, was repressed compared to untreated Ps. aeruginosa PAO1, confirming that ascorbate QS inhibition works on gene expression at the molecular level. CONCLUSION: Sodium ascorbate, even at low concentrations, inhibited QS and related virulence factors of Ps. aeruginosa PAO1. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated that sodium ascorbate could function as signal modulator and virulence inhibitor in Ps. aeruginosa.