Sinefungin, a Natural Nucleoside Analogue of S-Adenosylmethionine, Inhibits Streptococcus pneumoniae Biofilm GrowthReportar como inadecuado

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BioMed Research International - Volume 2014 2014, Article ID 156987, 10 pages -

Research Article

Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul 135-705, Republic of Korea

Department of Otorhinolaryngology-Head and Neck Surgery, Dongguk University Ilsan Hospital, Gyeonggi, Goyang 410-773, Republic of Korea

Received 5 February 2014; Revised 5 June 2014; Accepted 8 June 2014; Published 23 June 2014

Academic Editor: Meirong Zhao

Copyright © 2014 Mukesh Kumar Yadav et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Pneumococcal colonization and disease is often associated with biofilm formation, in which the bacteria exhibit elevated resistance both to antibiotics and to host defense systems, often resulting in infections that are persistent and difficult to treat. We evaluated the effect of sinefungin, a nucleoside analogue of S-adenosylmethionine, on pneumococcal in vitro biofilm formation and in vivo colonization. Sinefungin is bacteriostatic to pneumococci and significantly decreased biofilm growth and inhibited proliferation and structure of actively growing biofilms but did not alter growth or the matrix structure of established biofilms. Sinefungin significantly reduced pneumococcal colonization in rat middle ear. The quorum sensing molecule autoinducer-2 production was significantly reduced by 92% in sinefungin treated samples. The luxS, pfs, and speE genes were downregulated in biofilms grown in the presence of sinefungin. This study shows that sinefungin inhibits pneumococcal biofilm growth in vitro and colonization in vivo, decreases AI-2 production, and downregulates luxS, pfs, and speE gene expressions. Therefore, the S-adenosylmethionine SAM inhibitors could be used as lead compounds for the development of novel antibiofilm agents against pneumococci.

Autor: Mukesh Kumar Yadav, Seok-Won Park, Sung-Won Chae, and Jae-Jun Song



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