Thiol-benzo-triazolo-quinazolinone Inhibits Alg44 Binding to c-di-GMP and Reduces Alginate Production by Pseudomonas aeruginosa

ACS Chemical Biology
Eric ZhouVincent T Lee

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that affects a large proportion of cystic fibrosis (CF) patients. CF patients have dehydrated mucus within the airways that leads to the inability of the mucociliary escalator to expel inhaled microbes. Once inhaled, P. aeruginosa can persist in the lungs of the CF patients for the remainder of their lives. During this chronic infection, a phenomenon called mucoid conversion can occur in which P. aeruginosa can mutate and inactivate their mucA gene. As a consequence, transcription of the alg operon is highly expressed, leading to the copious secretion of the alginate exopolysaccharide, which is associated with decreased lung function and increased CF patient morbidity and mortality. Alginate biosynthesis by P. aeruginosa is post-translationally regulated by bis(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), which binds to the receptor protein Alg44 to activate alginate production. The identification of small molecules that disrupt the binding of c-di-GMP to Alg44 could inhibit the ability of P. aeruginosa to produce alginate. In this work, a class of thiol-benzo-triazolo-quinazolinone compounds that inhibited Alg44 binding to c-di-GMP in vitro was identified after s...Continue Reading

References

Nov 1, 1991·Antimicrobial Agents and Chemotherapy·N A Hodges, C A Gordon
Sep 1, 1968·Analytical Biochemistry·C A Knutson, A Jeanes
Jan 8, 1999·Journal of the American Society for Mass Spectrometry·Z Zhang, A G Marshall
Apr 5, 2002·Clinical Microbiology Reviews·Jeffrey B LyczakGerald B Pier
Feb 3, 2005·JAMA : the Journal of the American Medical Association·Zhanhai LiMark L Splaingard
Aug 10, 2005·The Journal of Biological Chemistry·Robert TarranRichard C Boucher
Oct 27, 2005·Bioinformatics·Dorit Amikam, Michael Y Galperin
Feb 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Nicole T LiberatiFrederick M Ausubel
Feb 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Hemantha KulasakaraStephen Lory
Mar 24, 2006·Nature·David C GadsbyLászló Csanády
May 12, 2006·Proceedings of the National Academy of Sciences of the United States of America·Eric E SmithMaynard V Olson
Aug 31, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kevin G RoelofsVincent T Lee
Oct 13, 2011·Frontiers in Microbiology·Michael J FranklinP Lynne Howell
Mar 9, 2013·Microbiology and Molecular Biology Reviews : MMBR·Ute RömlingMark Gomelsky
Mar 31, 2015·The Journal of Biological Chemistry·John C WhitneyP Lynne Howell
Jun 10, 2015·Journal of Bacteriology·Shan-Ho Chou, Michael Y Galperin

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Citations

Nov 19, 2019·Frontiers in Chemistry·Katrine QvortrupTim Tolker-Nielsen
Jan 30, 2020·Nature Reviews. Microbiology·M Fata Moradali, Bernd H A Rehm
Dec 7, 2018·Current Protocols in Molecular Biology·Anna B SeminaraVincent T Lee
Nov 21, 2020·International Journal of Molecular Sciences·Minh Tam Tran ThiBernd H A Rehm
Apr 20, 2021·ACS Infectious Diseases·Soo-Kyoung KimVincent T Lee
Jan 8, 2022·Future Medicinal Chemistry·Sanaz AhmadipourGavin J Miller

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