Small-molecule inhibitors of the pseudaminic acid biosynthetic pathway: Targeting motility as a key bacterial virulence factor

Antimicrobial Agents and Chemotherapy

Volumn 58, Issue 12, 2014, Pages 7430-7440

  Ménard, Robert ^a   Schoenhofen, Ian C ^a   Tao, Limei ^a   Aubry, Annie ^a   Bouchard, Patrice ^a   Reid, Christopher W ^a,b   Lachance, Paule ^a   Twine, Susan M ^a   Fulton, Kelly M ^a   Cui, Qizhi ^a   Hogues, Hervé ^a   Purisima, Enrico O ^a   Sulea, Traian ^a   Logan, Susan M ^a  

^a NATIONAL RESEARCH COUNCIL CANADA   (Canada)

^b BRYANT UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; BACTERIAL ENZYME; FLAGELLIN; PSEB ENZYME; PSEC ENZYME; PSEG ENZYME; PSEH ENZYME; PSEI ENZYME; PSEUDAMINIC ACID; PSEUDAMINIC ACID INHIBITOR; SMALL MOLECULE INHIBITOR; UNCLASSIFIED DRUG; VIRULENCE FACTOR; 5,7-DIACETAMIDO-3,5,7,9-TETRADEOXYNONULOSONIC ACID; MOLECULAR LIBRARY; SUGAR ACID;

ANTIBACTERIAL ACTIVITY; ARTICLE; BACTERIAL COLONIZATION; BACTERIAL FLAGELLUM; BACTERIAL VIRULENCE; BINDING AFFINITY; BIOSYNTHESIS; CAMPYLOBACTER JEJUNI; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG TARGETING; GLYCOSYLATION; HELICOBACTER PYLORI; HIGH THROUGHPUT SCREENING; HOST PATHOGEN INTERACTION; IC50; IN VITRO STUDY; MOLECULAR DOCKING; NONHUMAN; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; CELL MEMBRANE; CELL MEMBRANE PERMEABILITY; CHEMISTRY; COMPUTER INTERFACE; DRUG DEVELOPMENT; DRUG EFFECTS; FLAGELLUM; GENE EXPRESSION; GENETICS; METABOLISM; MOLECULAR LIBRARY; MOVEMENT (PHYSIOLOGY); PATHOGENICITY; PHARMACOLOGY; TRANSPORT AT THE CELLULAR LEVEL; VIRULENCE;

ANTI-BACTERIAL AGENTS; BIOLOGICAL TRANSPORT; CELL MEMBRANE; CELL MEMBRANE PERMEABILITY; DRUG DISCOVERY; FLAGELLA; FLAGELLIN; GENE EXPRESSION; GLYCOSYLATION; HELICOBACTER PYLORI; HIGH-THROUGHPUT SCREENING ASSAYS; MOLECULAR DOCKING SIMULATION; MOVEMENT; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP; SUGAR ACIDS; USER-COMPUTER INTERFACE; VIRULENCE;

EID: 84912075755     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.03858-14     Document Type: Article

References (44)

1. Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, Scheld M, Spellberg B, Bartlett J. 2009. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48:1-12. http://dx.doi.org/10.1086/595011.
2. Infectious Diseases Society of America. 2010. The 10 × '20 initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin. Infect. Dis. 50:1081-1083. http://dx.doi.org/10.1086/652237.
3. Barczak AK, Hung DT. 2009. Productive steps toward an antimicrobial targeting virulence. Curr. Opin. Microbiol. 12:490-496. http://dx.doi.org /10.1016/j.mib.2009.06.012.
4. Cegelski L, Marshall GR, Eldridge GR, Hultgren SJ. 2008. The biology and future prospects of antivirulence therapies. Nat. Rev. Microbiol. 6:17-27. http://dx.doi.org/10.1038/nrmicro1818.
5. Rasko DA, Sperandio V. 2010. Anti-virulence strategies to combat bac-teria-mediated disease. Nat. Rev. Drug Discov. 9:117-128. http://dx.doi .org/10.1038/nrd3013.
6. Allen RC, Popat R, Diggle SP, Brown SP. 2014. Targeting virulence: can we make evolution-proof drugs? Nat. Rev. Microbiol. 12:300-308. http: //dx.doi.org/10.1038/nrmicro3232.
7. Suerbaum S, Michetti P. 2002. Helicobacter pylori infection. N. Engl. J. Med. 347:1175-1186. http://dx.doi.org/10.1056/NEJMra020542.
8. Urgesi R, Cianci R, Riccioni ME. 2012. Update on triple therapy for eradication of Helicobacter pylori: current status of the art. Clin. Exp. Gastroenterol. 5:151-157. http://dx.doi.org/10.2147/CEG.S25416.
9. Schirm M, Soo EC, Aubry AJ, Austin J, Thibault P, Logan SM. 2003. Structural, genetic and functional characterization of the flagellin glycosylation process in Helicobacter pylori. Mol. Microbiol. 48:1579-1592. http://dx.doi.org/10.1046/j.1365-2958.2003.03527.x.
10. Eaton KA, Suerbaum S, Josenhans C, Krakowka S. 1996. Colonization of gnotobiotic piglets by Helicobacter pylori deficient in two flagellin genes. Infect. Immun. 64:2445-2448.
11. Ottemann KM, Lowenthal AC. 2002. Helicobacter pylori uses motility for initial colonization and to attain robust infection. Infect. Immun. 70: 1984-1990. http://dx.doi.org/10.1128/IAI.70.4.1984-1990.2002.
12. Aihara E, Closson C, Matthis AL, Schumacher MA, Engevik AC, Zavros Y, Ottemann KM, Montrose MH. 2014. Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori. PLoS Pathog. 10:e1004275. http://dx.doi.org/10.1371/journal.ppat .1004275.
13. Monack DM. 2013. Helicobacter and Salmonella persistent infection strategies. Cold Spring Harb Perspect Med. 3:a010348. http://dx.doi.org/10 .1101/cshperspect.a010348.
14. Van Zanten SJ, Dixon MF, Lee A. 1999. The gastric transitional zones: neglected links between gastroduodenal pathology and Helicobacter ecology. Gastroenterology 116:1217-1229. http://dx.doi.org/10.1016/S0016 -5085(99)70025-9.
15. Boonjakuakul JK, Canfield DR, Solnick JV. 2005. Comparison of Helicobacter pylori virulence gene expression in vitro and in the rhesus macaque. Infect. Immun. 73:4895-4904. http://dx.doi.org/10.1128/IAI.73.8 .4895-4904.2005.
16. Thibault P, Logan SM, Kelly JF, Brisson JR, Ewing CP, Trust TJ, Guerry P. 2001. Identification of the carbohydrate moieties and glycosylation motifs in Campylobacter jejuni flagellin. J. Biol. Chem. 276:34862-34870. http://dx.doi.org/10.1074/jbc.M104529200.
17. Guerry P, Ewing CP, Schirm M, Lorenzo M, Kelly J, Pattarini D, Majam G, Thibault P, Logan S. 2006. Changes in flagellin glycosylation affect Campylobacter autoagglutination and virulence. Mol. Microbiol. 60:299-311. http://dx.doi.org/10.1111/j.1365-2958.2006.05100.x.
18. Knirel YA, Vinogradov EV, L'Vov VL, Kocharova NA, Shashkov AS, Dmitriev BA, Kochetkov NK. 1984. Sialic acids of a new type from the lipopolysaccharides of Pseudomonas aeruginosa and Shigella boydii. Carbohydr. Res. 133:C5-C8. http://dx.doi.org/10.1016/0008-6215(84)85213-1.
19. Kenyon JJ, Marzaioli AM, Hall RM, De Castro C. 2014. Structure of the K2 capsule associated with the KL2 gene cluster of Acinetobacter baumannii. Glycobiology 24:554-563. http://dx.doi.org/10.1093/glycob/cwu024.
20. Kiss E, Reuhs BL, Kim JS, Kereszt A, Petrovics G, Putnoky P, Dusha I, Carlson RW, Kondorosi A. 1997. The rkpGHI and -J genes are involved in capsular polysaccharide production by Rhizobium meliloti. J. Bacteriol. 179:2132-2140.
21. Horzempa J, Dean CR, Goldberg JB, Castric P. 2006. Pseudomonas aeruginosa 1244 pilin glycosylation: glycan substrate recognition. J. Bacteriol. 188:4244-4252. http://dx.doi.org/10.1128/JB.00273-06.
22. Schoenhofen IC, McNally DJ, Brisson JR, Logan SM. 2006. Elucidation of the CMP-pseudaminic acid pathway in Helicobacter pylori: synthesis from UDP-N-acetylglucosamine by a single enzymatic reaction. Glycobiology 16:8C-14C. http://dx.doi.org/10.1093/glycob/cwl010.
23. Liu F, Tanner ME. 2006. PseG of pseudaminic acid biosynthesis: a UDPsugar hydrolase as a masked glycosyltransferase. J. Biol. Chem. 281:20902-20909. http://dx.doi.org/10.1074/jbc.M602972200.
24. Schoenhofen IC, McNally DJ, Vinogradov E, Whitfield D, Young NM, Dick S, Wakarchuk WW, Brisson JR, Logan SM. 2006. Functional characterization of dehydratase/aminotransferase pairs from Helicobacter and Campylobacter: enzymes distinguishing the pseudaminic acid and bacillosamine biosynthetic pathways. J. Biol. Chem. 281:723-732. http: //dx.doi.org/10.1074/jbc.M511021200.
25. Creuzenet C, Schur MJ, Li J, Wakarchuk WW, Lam JS. 2000. FlaA1, a new bifunctional UDP-GlcNAc C6 dehydratase/C4 reductase from Helicobacter pylori. J. Biol. Chem. 275:34873-34880. http://dx.doi.org/10.1074 /jbc.M006369200.
26. Schoenhofen IC, Lunin VV, Julien JP, Li Y, Ajamian E, Matte A, Cygler M, Brisson JR, Aubry A, Logan SM, Bhatia S, Wakarchuk WW, Young NM. 2006. Structural and functional characterization of PseC, an aminotransferase involved in the biosynthesis of pseudaminic acid, an essential flagellar modification in Helicobacter pylori. J. Biol. Chem. 281:8907-8916. http://dx.doi.org/10.1074/jbc.M512987200.
27. Rangarajan ES, Proteau A, Cui Q, Logan SM, Potetinova Z, Whitfield D, Purisima EO, Cygler M, Matte A, Sulea T, Schoenhofen IC. 2009. Structural and functional analysis of Campylobacter jejuni PseG: a UDPsugar hydrolase from the pseudaminic acid biosynthetic pathway. J. Biol. Chem. 284:20989-21000. http://dx.doi.org/10.1074/jbc.M109.012351.
28. Ishiyama N, Creuzenet C, Miller WL, Demendi M, Anderson EM, Harauz G, Lam JS, Berghuis AM. 2006. Structural studies of FlaA1 from Helicobacter pylori reveal the mechanism for inverting 4,6-dehydratase activity. J. Biol. Chem. 281:24489-24495. http://dx.doi.org/10.1074/jbc .M602393200.
29. Schoenhofen IC, Vinogradov E, Whitfield DM, Brisson JR, Logan SM. 2009. The CMP-legionaminic acid pathway in Campylobacter: biosynthesis involving novel GDP-linked precursors. Glycobiology 19:715-725. http://dx.doi.org/10.1093/glycob/cwp039.
30. Riazi A, Strong PC, Coleman R, Chen W, Hirama T, van Faassen H, Henry M, Logan SM, Szymanski CM, Mackenzie R, Ghahroudi MA. 2013. Pentavalent single-domain antibodies reduce Campylobacter jejuni motility and colonization in chickens. PLoS One 8:e83928. http://dx.doi .org/10.1371/journal.pone.0083928.
31. Irwin JJ, Shoichet BK. 2005. ZINC-a free database of commercially available compounds for virtual screening. J. Chem. Inf. Model. 45:177-182. http://dx.doi.org/10.1021/ci049714-.
32. Sulea T, Hogues H, Purisima EO. 2012. Exhaustive search and solvated interaction energy (SIE) for virtual screening and affinity prediction. J. Comput. Aided Mol. Des. 26:617-633. http://dx.doi.org/10.1007/s10822 -011-9529-7.
33. Hogues H, Sulea T, Purisima EO. 2014. Exhaustive docking and solvated interaction energy scoring: lessons learned from the SAMPL4 challenge. J. Comput. Aided Mol. Des. 28:417-427. http://dx.doi.org/10.1007/s10822 -014-9715-5.
34. Sulea T, Cui Q, Purisima EO. 2011. Solvated interaction energy (SIE) for scoring protein-ligand binding affinities. 2. Benchmark in the CSAR-2010 scoring exercise. J. Chem. Inf. Model. 51:2066-2081. http://dx.doi.org/10 .1021/ci2000242.
35. Naim M, Bhat S, Rankin KN, Dennis S, Chowdhury SF, Siddiqi I, Drabik P, Sulea T, Bayly CI, Jakalian A, Purisima EO. 2007. Solvated interaction energy (SIE) for scoring protein-ligand binding affinities. 1. Exploring the parameter space. J. Chem. Inf. Model. 47:122-133. http://dx .doi.org/10.1021/ci600406v.
36. Sulea T, Purisima EO. 2012. The solvated interaction energy method for scoring binding affinities. Methods Mol. Biol. 819:295-303. http://dx.doi .org/10.1007/978-1-61779-465-0-19.
37. Cui Q, Sulea T, Schrag JD, Munger C, Hung MN, Naim M, Cygler M, Purisima EO. 2008. Molecular dynamics-solvated interaction energy studies of protein-protein interactions: the MP1-p14 scaffolding complex. J. Mol. Biol. 379:787-802. http://dx.doi.org/10.1016/j.jmb.2008.04.035.
38. Ozbal CC, LaMarr WA, Linton JR, Green DF, Katz A, Morrison TB, Brenan CJ. 2004. High throughput screening via mass spectrometry: a case study using acetylcholinesterase. Assay Drug Dev. Technol. 2:373-381. http://dx.doi.org/10.1089/adt.2004.2.373.
39. McGovern SL, Caselli E, Grigorieff N, Shoichet BK. 2002. A common mechanism underlying promiscuous inhibitors from virtual and highthroughput screening. J. Med. Chem. 45:1712-1722. http://dx.doi.org/10 .1021/jm010533y.
40. Coan KE, Maltby DA, Burlingame AL, Shoichet BK. 2009. Promiscuous aggregate-based inhibitors promote enzyme unfolding. J. Med. Chem. 52:2067-2075. http://dx.doi.org/10.1021/jm801605r.
41. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. 2001. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46:3-26. http://dx.doi.org/10.1016/S0169-409X(00)00129-0.
42. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. 2002. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 45: 2615-2623. http://dx.doi.org/10 .1021/jm020017n.
43. McNally DJ, Hui JP, Aubry AJ, Mui KK, Guerry P, Brisson JR, Logan SM, Soo EC. 2006. Functional characterization of the flagellar glycosylation locus in Campylobacter jejuni 81-176 using a focused metabolomics approach. J. Biol. Chem. 281:18489-18498. http://dx.doi.org/10.1074/jbc .M603777200.
44. Gatta L, Vakil N, Vaira D, Scarpignato C. 2013. Global eradication rates for Helicobacter pylori infection: systematic review and meta-analysis of sequential therapy. BMJ 347:f4587. http://dx.doi.org/10.1136/bmj.f4587.