دورية أكاديمية
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The Small Molecule DAM Inhibitor, Pyrimidinedione, Disrupts Streptococcus pneumoniae Biofilm Growth In Vitro.

التفاصيل البيبلوغرافية
العنوان: The Small Molecule DAM Inhibitor, Pyrimidinedione, Disrupts Streptococcus pneumoniae Biofilm Growth In Vitro.
المؤلفون: Yadav MK; Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea; Institute for Medical Device Clinical Trials, Korea University College of Medicine, Seoul, South Korea., Go YY; Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea., Chae SW; Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea., Song JJ; Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
المصدر: PloS one [PLoS One] 2015 Oct 02; Vol. 10 (10), pp. e0139238. Date of Electronic Publication: 2015 Oct 02 (Print Publication: 2015).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Anti-Infective Agents/*metabolism , Biofilms/*drug effects , Methyltransferases/*antagonists & inhibitors , Small Molecule Libraries/*pharmacology , Streptococcus pneumoniae/*drug effects, Cell Line ; DNA, Bacterial/genetics ; Down-Regulation/drug effects ; Epithelium/microbiology ; Gene Expression Regulation, Bacterial/drug effects ; Humans ; Plankton/drug effects ; Pneumococcal Infections/drug therapy ; Quorum Sensing/drug effects ; Streptococcus pneumoniae/genetics ; Up-Regulation/drug effects ; Virulence/drug effects
مستخلص: Streptococcus pneumoniae persist in the human nasopharynx within organized biofilms. However, expansion to other tissues may cause severe infections such as pneumonia, otitis media, bacteremia, and meningitis, especially in children and the elderly. Bacteria within biofilms possess increased tolerance to antibiotics and are able to resist host defense systems. Bacteria within biofilms exhibit different physiology, metabolism, and gene expression profiles than planktonic cells. These differences underscore the need to identify alternative therapeutic targets and novel antimicrobial compounds that are effective against pneumococcal biofilms. In bacteria, DNA adenine methyltransferase (Dam) alters pathogenic gene expression and catalyzes the methylation of adenine in the DNA duplex and of macromolecules during the activated methyl cycle (AMC). In pneumococci, AMC is involved in the biosynthesis of quorum sensing molecules that regulate competence and biofilm formation. In this study, we examine the effect of a small molecule Dam inhibitor, pyrimidinedione, on Streptococcus pneumoniae biofilm formation and evaluate the changes in global gene expression within biofilms via microarray analysis. The effects of pyrimidinedione on in vitro biofilms were studied using a static microtiter plate assay, and the architecture of the biofilms was viewed using confocal and scanning electron microscopy. The cytotoxicity of pyrimidinedione was tested on a human middle ear epithelium cell line by CCK-8. In situ oligonucleotide microarray was used to compare the global gene expression of Streptococcus pneumoniae D39 within biofilms grown in the presence and absence of pyrimidinedione. Real-time RT-PCR was used to study gene expression. Pyrimidinedione inhibits pneumococcal biofilm growth in vitro in a concentration-dependent manner, but it does not inhibit planktonic cell growth. Confocal microscopy analysis revealed the absence of organized biofilms, where cell-clumps were scattered and attached to the bottom of the plate when cells were grown in the presence of pyrimidinedione. Scanning electron microscopy analysis demonstrated the absence of an extracellular polysaccharide matrix in pyrimidinedione-grown biofilms compared to control-biofilms. Pyrimidinedione also significantly inhibited MRSA, MSSA, and Staphylococcus epidermidis biofilm growth in vitro. Furthermore, pyrimidinedione does not exhibit eukaryotic cell toxicity. In a microarray analysis, 56 genes were significantly up-regulated and 204 genes were significantly down-regulated. Genes involved in galactose metabolism were exclusively up-regulated in pyrimidinedione-grown biofilms. Genes related to DNA replication, cell division and the cell cycle, pathogenesis, phosphate-specific transport, signal transduction, fatty acid biosynthesis, protein folding, homeostasis, competence, and biofilm formation were down regulated in pyrimidinedione-grown biofilms. This study demonstrated that the small molecule Dam inhibitor, pyrimidinedione, inhibits pneumococcal biofilm growth in vitro at concentrations that do not inhibit planktonic cell growth and down regulates important metabolic-, virulence-, competence-, and biofilm-related genes. The identification of a small molecule (pyrimidinedione) with S. pneumoniae biofilm-inhibiting capabilities has potential for the development of new compounds that prevent biofilm formation.
References: Laryngoscope. 2007 Apr;117(4):668-73. (PMID: 17415138)
Laryngoscope. 2008 Jan;118(1):128-34. (PMID: 17975509)
Nat Rev Microbiol. 2008 Aug;6(8):613-24. (PMID: 18628769)
Eur J Clin Microbiol Infect Dis. 2008 Aug;27(8):635-42. (PMID: 18322716)
J Bacteriol. 2008 Oct;190(19):6330-9. (PMID: 18658260)
Clin Infect Dis. 2008 Dec 1;47 Suppl 3:S202-6. (PMID: 18986290)
Methods. 2001 Dec;25(4):402-8. (PMID: 11846609)
Science. 2002 Feb 22;295(5559):1487. (PMID: 11859186)
Appl Environ Microbiol. 2002 Mar;68(3):1196-203. (PMID: 11872468)
J Bacteriol. 1998 Nov;180(21):5727-32. (PMID: 9791125)
FEMS Microbiol Rev. 2009 May;33(3):488-503. (PMID: 19175412)
J Antimicrob Chemother. 2009 Jun;63(6):1163-72. (PMID: 19376840)
Lancet. 2009 Oct 31;374(9700):1543-56. (PMID: 19880020)
Microb Pathog. 2010 Mar-Apr;48(3-4):124-30. (PMID: 20096771)
Diagn Microbiol Infect Dis. 2010 Aug;67(4):311-8. (PMID: 20638597)
PLoS Pathog. 2010;6(8):e1001044. (PMID: 20714350)
J Infect Dis. 2010 Oct 1;202(7):1068-75. (PMID: 20715928)
Mol Microbiol. 2011 Jan;79(1):7-20. (PMID: 21166890)
Inflamm Allergy Drug Targets. 2011 Apr;10(2):141-57. (PMID: 21314623)
PLoS One. 2011;6(5):e19844. (PMID: 21611130)
Int J Pediatr Otorhinolaryngol. 2012 Mar;76(3):334-8. (PMID: 22209256)
Infect Immun. 2012 Aug;80(8):2744-60. (PMID: 22645283)
Appl Environ Microbiol. 2012 Aug;78(16):5597-605. (PMID: 22660715)
Expert Rev Vaccines. 2012 Jul;11(7):841-55. (PMID: 22913260)
Microb Pathog. 2012 Nov-Dec;53(5-6):219-26. (PMID: 22963864)
Trends Microbiol. 2013 Mar;21(3):129-35. (PMID: 23273566)
Pediatr Clin North Am. 2013 Apr;60(2):391-407. (PMID: 23481107)
Med Clin North Am. 2013 Jul;97(4):647-66, x-xi. (PMID: 23809718)
PLoS One. 2014;9(5):e97314. (PMID: 24823499)
Biomed Res Int. 2014;2014:156987. (PMID: 25050323)
Appl Environ Microbiol. 2014 Sep;80(17):5349-58. (PMID: 24951784)
Antimicrob Agents Chemother. 2015 Jan;59(1):76-84. (PMID: 25313216)
Clin Microbiol Rev. 2002 Apr;15(2):167-93. (PMID: 11932229)
J Bacteriol. 2002 Jul;184(13):3450-6. (PMID: 12057938)
Ann Otol Rhinol Laryngol. 2002 Jun;111(6):507-17. (PMID: 12090706)
J Bacteriol. 2003 Jan;185(1):349-58. (PMID: 12486073)
Lancet. 2004 Jun 5;363(9424):1871-2. (PMID: 15183627)
PLoS One. 2015;10(3):e0119564. (PMID: 25781975)
PLoS One. 2013;8(6):e67147. (PMID: 23825636)
Cell Mol Life Sci. 2009 Feb;66(4):636-48. (PMID: 18953685)
Microbiol Mol Biol Rev. 2001 Jun;65(2):187-207 ; first page, table of contents. (PMID: 11381099)
Infect Immun. 2001 Dec;69(12):7197-204. (PMID: 11705888)
FEMS Microbiol Lett. 2001 Nov 27;205(1):99-104. (PMID: 11728722)
Res Microbiol. 1996 Jul-Sep;147(6-7):518-22. (PMID: 9084764)
J Bacteriol. 1997 Jun;179(12):4043-5. (PMID: 9190823)
Mol Microbiol. 1997 Jun;24(5):895-904. (PMID: 9219998)
Mol Microbiol. 2004 Jul;53(2):651-64. (PMID: 15228541)
Infect Immun. 2004 Oct;72(10):5582-96. (PMID: 15385455)
Clin Exp Immunol. 2004 Nov;138(2):195-201. (PMID: 15498026)
Mol Microbiol. 1991 Mar;5(3):575-84. (PMID: 1904524)
Infect Immun. 1998 Dec;66(12):5620-9. (PMID: 9826334)
J Bacteriol. 1999 Feb;181(4):1126-33. (PMID: 9973337)
Science. 1999 May 7;284(5416):967-70. (PMID: 10320378)
Science. 1999 May 21;284(5418):1318-22. (PMID: 10334980)
J Bacteriol. 1999 Aug;181(16):5004-16. (PMID: 10438773)
J Bacteriol. 1999 Sep;181(17):5135-9. (PMID: 10464180)
Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11578-83. (PMID: 10500219)
Curr Opin Microbiol. 2005 Apr;8(2):154-60. (PMID: 15802246)
Microbiology. 2005 Jul;151(Pt 7):2291-9. (PMID: 16000719)
J Bacteriol. 2005 Dec;187(24):8340-9. (PMID: 16321938)
Mol Microbiol. 2006 Jan;59(2):551-66. (PMID: 16390449)
Microbes Infect. 2006 Jan;8(1):145-53. (PMID: 16182588)
JAMA. 2006 Jul 12;296(2):202-11. (PMID: 16835426)
J Clin Microbiol. 2006 Aug;44(8):2721-7. (PMID: 16891483)
Mol Microbiol. 2006 Sep;61(5):1196-210. (PMID: 16925554)
J Biomol Screen. 2006 Aug;11(5):497-510. (PMID: 16760373)
J Cell Physiol. 2006 Dec;209(3):701-5. (PMID: 17001680)
J Bacteriol. 2006 Nov;188(22):7785-95. (PMID: 16936041)
Int J Med Microbiol. 2007 Feb;297(1):1-7. (PMID: 17126598)
J Antimicrob Chemother. 2007 Feb;59(2):301-4. (PMID: 17142818)
المشرفين على المادة: 0 (Anti-Infective Agents)
0 (DNA, Bacterial)
0 (Small Molecule Libraries)
EC 2.1.1.- (Methyltransferases)
تواريخ الأحداث: Date Created: 20151003 Date Completed: 20160607 Latest Revision: 20181113
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC4592238
DOI: 10.1371/journal.pone.0139238
PMID: 26431532
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0139238