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Title 

Vinaxanthone, a new FabI inhibitor from Penicillium sp.

Authors 

C J ZhengMi Jin SohnWon Gon Kim

Publisher 

Oxford University Press (OUP)

Issue Date 

2009

Citation 

Journal of Antimicrobial Chemotherapy, vol. 63, no. 5, pp. 949-953

Keywords 

antibacterialEnoyl-ACP reductasefatty acid synthesisstaphylococcus aureustarget validation

Abstract 

Objectives: Bacterial enoyl-ACP reductase (FabI) has been validated as a novel antibacterial target for tackling infections caused by multidrug-resistant pathogens. A few FabI inhibitors, however, are known. This study isolated a new FabI inhibitor from Penicillium sp. Methods: A screening programme led to the selection of a Penicillium sp. producing a strong FabI-inhibitory metabolite. The chemical structure of the isolated FabI inhibitor was elucidated by mass spectrometry and nuclear magnetic resonance spectral data. The antibacterial target of the inhibitor was validated by overexpression assays. Results: The isolated FabI inhibitor was elucidated to be vinaxanthone. It selectively inhibited Staphylococcus aureus FabI with an IC50 of 0.9 μM; it did not affect FabK, an enoyl-ACP reductase of Streptococcus pneumoniae. Consistent with its inhibition of FabI, the inhibitor prevented intracellular fatty acid synthesis while it did not affect protein biosynthesis. It also prevented the growth of S. aureus as well as methicillin-resistant S. aureus (MRSA) and quinolone-resistant S. aureus. Importantly, fabI -overexpressing S. aureus showed reduced susceptibility to the inhibitor compared with the wild-type strain, demonstrating that its antibacterial action is mediated by inhibition of FabI. Conclusions: Vinaxanthone is a new FabI-directed antibacterial of natural origin that could have potential for further development as a new anti-MRSA agent.

ISSN 

0305-7453

Link 

http://dx.doi.org/10.1093/jac/dkp058

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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