title: Sinefungin, a natural nucleoside analogue of S-adenosylmethionine, inhibits Streptococcus pneumoniae biofilm growth.
abstract: 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.
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul 135-705, Republic of Korea.
authors: Mukesh Kumar
authors: 0000-0002-4703-8554
authors: MK
authors: Yadav
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Dongguk University Ilsan Hospital, Gyeonggi, Goyang 410-773, Republic of Korea.
authors: Seok-Won
authors: SW
authors: Park
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul 135-705, Republic of Korea.
authors: Sung-Won
authors: SW
authors: Chae
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul 135-705, Republic of Korea.
authors: Jae-Jun
authors: 0000-0002-8488-9091
authors: JJ
authors: Song
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D015169:Colony Count, Microbial; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006710:Homocysteine / Q000096:biosynthesis; D010033:Otitis Media / Q000382:microbiology / Q000473:pathology; D010933:Plankton / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000031:analogs & derivatives*; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000254:growth & development / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D006710:Homocysteine; D012436:S-Adenosylmethionine; D000241:Adenosine; C006235:sinefungin