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Title 

Meleagrin, a new FabI inhibitor from Penicillium chryosogenum with at least one additional mode of action

Authors 

C J ZhengM J SohnSangku LeeWon Gon Kim

Publisher 

Public Library of Science

Issue Date 

2013

Citation 

Plos One, vol. 8, no. 11, pp. e78922-e78922

Abstract 

Bacterial enoyl-acyl carrier protein reductase (FabI) is a promising novel antibacterial target. We isolated a new class of FabI inhibitor from Penicillium chrysogenum, which produces various antibiotics, the mechanisms of some of them are unknown. The isolated FabI inhibitor was determined to be meleagrin by mass spectroscopy and nuclear magnetic resonance spectral analyses, and its more active and inactive derivatives were chemically prepared. Consistent with their selective inhibition of Staphylococcus aureus FabI, meleagrin and its more active derivatives directly bound to S. aureus FabI in a fluorescence quenching assay, inhibited intracellular fatty acid biosynthesis and growth of S. aureus, and increased the minimum inhibitory concentration for fabI-overexpressing S. aureus. The compounds that were not effective against the FabK isoform, however, inhibited the growth of Streptococcus pneumoniae that contained only the FabK isoform. Additionally no resistant mutant to the compounds was obtained. Importantly, fabK-overexpressing Escherichia coli was not resistant to these compounds, but was resistant to triclosan. These results demonstrate that the compounds inhibited another target in addition to FabI. Thus, meleagrin is a new class of FabI inhibitor with at least one additional mode of action that could have potential for treating multidrug-resistant bacteria

ISSN 

1932-6203

Link 

http://dx.doi.org/10.1371/journal.pone.0078922

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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