Inhibition of Pseudomonas aeruginosa ExsA DNA-binding activity by N-hydroxybenzimidazoles

Antimicrobial Agents and Chemotherapy

Volumn 60, Issue 2, 2016, Pages 766-776

  Marsden, Anne E ^a   King, Jessica M ^a   Spies, M Ashley ^b   Kim, Oak K ^c   Yahr, Timothy L ^a  

^a UNIVERSITY OF IOWA   (United States)

^b UNIVERSITY OF IOWA   (United States)

^c Transcept Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; BACTERIAL PROTEIN; BENZIMIDAZOLE DERIVATIVE; DNA; DNA BINDING PROTEIN; EXSA PROTEIN; LCRF PROTEIN; UNCLASSIFIED DRUG; VFR PROTEIN; CYCLIC AMP BINDING PROTEIN; EXSA PROTEIN, PSEUDOMONAS AERUGINOSA; HYBRID PROTEIN; LCRF PROTEIN, YERSINIA PESTIS; TRANSACTIVATOR PROTEIN; TYPE III SECRETION SYSTEM; VFR PROTEIN, PSEUDOMONAS AERUGINOSA;

AEROMONAS HYDROPHILA; ARTICLE; BACTERIAL GENE; COCULTURE; COMPUTER MODEL; CONTROLLED STUDY; CYTOTOXICITY; DNA BINDING; DNA BINDING ASSAY; GENE EXPRESSION; IC50; MAMMAL CELL; MOLECULAR DOCKING; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INTERACTION; PSEUDOMONAS AERUGINOSA; SITE DIRECTED MUTAGENESIS; VIBRIO PARAHAEMOLYTICUS; YERSINIA PESTIS; AMINO ACID SEQUENCE; ANTAGONISTS AND INHIBITORS; BINDING SITE; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MOLECULAR GENETICS; PATHOGENICITY; PROMOTER REGION; TYPE III SECRETION SYSTEM;

AMINO ACID SEQUENCE; BACTERIAL PROTEINS; BENZIMIDAZOLES; BINDING SITES; CYCLIC AMP RECEPTOR PROTEIN; DNA-BINDING PROTEINS; GENE EXPRESSION REGULATION, BACTERIAL; MOLECULAR SEQUENCE DATA; PROMOTER REGIONS, GENETIC; PSEUDOMONAS AERUGINOSA; RECOMBINANT FUSION PROTEINS; TRANS-ACTIVATORS; TYPE III SECRETION SYSTEMS; YERSINIA PESTIS;

EID: 84957890549     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.02242-15     Document Type: Article

References (42)

1. Rice LB. 2008. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis 197:1079-1081. http://dx.doi.org/10.1086/533452.
2. Pendleton JN, Gorman SP, Gilmore BF. 2013. Clinical relevance of the ESKAPE pathogens. Expert Rev Anti Infect Ther 11:297-308. http://dx.doi.org/10.1586/eri.13.12.
3. Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, Fridkin SK, National Healthcare Safety Network Team, Participating National Healthcare Safety Network Facilities. 2008. NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007. Infect Control Hosp Epidemiol 29:996-1011. http://dx.doi.org/10.1086/591861.
4. Sievert DM, Ricks P, Edwards JR, Schneider A, Patel J, Srinivasan A, Kallen A, Limbago B, Fridkin S. 2013. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010. Infect Control Hosp Epidemiol 34:1-14. http://dx.doi.org/10.1086/668770.
5. Rice LB. 2006. Challenges in identifying new antimicrobial agents effective for treating infections with Acinetobacter baumannii and Pseudomonas aeruginosa. Clin Infect Dis 43(Suppl 2):S100-S105. http://dx.doi.org/10.1086/504487.
6. Zilberberg MD, Shorr AF. 2013. Prevalence of multidrug-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae among specimens from hospitalized patients with pneumonia and bloodstream infections in the United States from 2000 to 2009. J Hosp Med 8:559-563. http://dx.doi.org/10.1002/jhm.2080.
7. Nathwani D, Raman G, Sulham K, Gavaghan M, Menon V. 2014. Clinical and economic consequences of hospital-acquired resistant and multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis. Antimicrob Resist Infect Control 3:32. http://dx.doi.org/10.1186/2047-2994-3-32.
8. Lee VT, Pukatzki S, Sato H, Kikawada E, Kazimirova AA, Huang J, Li X, Arm JP, Frank DW, Lory S. 2007. Pseudolipasin A is a specific inhibitor for phospholipase A2 activity of Pseudomonas aeruginosa cytotoxin ExoU. Infect Immun 75:1089-1098. http://dx.doi.org/10.1128/IAI.01184-06.
9. Arnoldo A, Curak J, Kittanakom S, Chevelev I, Lee VT, Sahebol-Amri M, Koscik B, Ljuma L, Roy PJ, Bedalov A, Giaever G, Nislow C, Merrill AR, Lory S, Stagljar I. 2008. Identification of small molecule inhibitors of Pseudomonas aeruginosa exoenzyme S using a yeast phenotypic screen. PLoS Genet 4:e1000005. http://dx.doi.org/10.1371/journal.pgen.1000005.
10. Aiello D, Williams JD, Majgier-Baranowska H, Patel I, Peet NP, Huang J, Lory S, Bowlin TL, Moir DT. 2010. Discovery and characterization of inhibitors of Pseudomonas aeruginosa type III secretion. Antimicrob Agents Chemother 54:1988-1999. http://dx.doi.org/10.1128/AAC.01598-09.
11. Bowlin NO, Williams JD, Knoten CA, Torhan MC, Tashjian TF, Li B, Aiello D, Mecsas J, Hauser AR, Peet NP, Bowlin TL, Moir DT. 2014. Mutations in the Pseudomonas aeruginosa needle protein gene pscF confer resistance to phenoxyacetamide inhibitors of the type III secretion system. Antimicrob Agents Chemother 58:2211-2220. http://dx.doi.org/10.1128/AAC.02795-13.
12. Williams JD, Torhan MC, Neelagiri VR, Brown C, Bowlin NO, Di M, McCarthy CT, Aiello D, Peet NP, Bowlin TL, Moir DT. 2015. Synthesis and structure-activity relationships of novel phenoxyacetamide inhibitors of the Pseudomonas aeruginosa type III secretion system (T3SS). Bioorg Med Chem 23:1027-1043. http://dx.doi.org/10.1016/j.bmc.2015.01.011.
13. Zetterström CE, Hasselgren J, Salin O, Davis RA, Quinn RJ, Sundin C, Elofsson M. 2013. The resveratrol tetramer (-)-hopeaphenol inhibits type III secretion in the gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa. PLoS One 8:e81969. http://dx.doi.org/10.1371/journal.pone.0081969.
14. Mahmood F, Hakimiyan A, Jayaraman V, Wood S, Sivaramakrishnan G, Rehman T, Reuhs BL, Chubinskaya S, Shafikhani SH. 2013. A novel human antimicrobial factor targets Pseudomonas aeruginosa through its type III secretion system. J Med Microbiol 62:531-539. http://dx.doi.org/10.1099/jmm.0.051227-0.
15. Wang J, Dong Y, Zhou T, Liu X, Deng Y, Wang C, Lee J, Zhang LH. 2013. Pseudomonas aeruginosa cytotoxicity is attenuated at high cell density and associated with the accumulation of phenylacetic acid. PLoS One 8:e60187. http://dx.doi.org/10.1371/journal.pone.0060187.
16. Rzhepishevska O, Hakobyan S, Ekstrand-Hammarstrom B, Nygren Y, Karlsson T, Bucht A, Elofsson M, Boily JF, Ramstedt M. 2014. The gallium(III)-salicylidene acylhydrazide complex shows synergistic antibiofilm effect and inhibits toxin production by Pseudomonas aeruginosa. J Inorg Biochem 138:1-8. http://dx.doi.org/10.1016/j.jinorgbio.2014.04.009.
17. Sawa T, Yahr TL, Ohara M, Kurahashi K, Gropper MA, Wiener-Kronish JP, Frank DW. 1999. Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury. Nat Med 5:392-398. http://dx.doi.org/10.1038/7391.
18. Warrener P, Varkey R, Bonnell JC, DiGiandomenico A, Camara M, Cook K, Peng L, Zha J, Chowdury P, Sellman B, Stover CK. 2014. A novel anti-PcrV antibody providing enhanced protection against Pseudomonas aeruginosa in multiple animal infection models. Antimicrob Agents Chemother 58:4384-4391. http://dx.doi.org/10.1128/AAC.02643-14.
19. Hauser AR. 2009. The type III secretion system of Pseudomonas aeruginosa: infection by injection. Nat Rev Microbiol 7:654-665. http://dx.doi.org/10.1038/nrmicro2199.
20. Diaz MR, King JM, Yahr TL. 2011. Intrinsic and extrinsic regulation of type III secretion gene expression in Pseudomonas aeruginosa. Front Microbiol 2:89. http://dx.doi.org/10.3389/fmicb.2011.00089.
21. Smith RS, Wolfgang MC, Lory S. 2004. An adenylate cyclase-controlled signaling network regulates Pseudomonas aeruginosa virulence in a mouse model of acute pneumonia. Infect Immun 72:1677-1684. http://dx.doi.org/10.1128/IAI.72.3.1677-1684.2004.
22. McCaw ML, Lykken GL, Singh PK, Yahr TL. 2002. ExsD is a negative regulator of the Pseudomonas aeruginosa type III secretion regulon. Mol Microbiol 46:1123-1133. http://dx.doi.org/10.1046/j.1365-2958.2002.03228.x.
23. Vallis AJ, Yahr TL, Barbieri JT, Frank DW. 1999. Regulation of ExoS production and secretion by Pseudomonas aeruginosa in response to tissue culture conditions. Infect Immun 67:914-920.
24. Brutinel ED, Vakulskas CA, Yahr TL. 2010. ExsD inhibits expression of the Pseudomonas aeruginosa type III secretion system by disrupting ExsA self-association and DNA binding activity. J Bacteriol 192:1479-1486. http://dx.doi.org/10.1128/JB.01457-09.
25. Thibault J, Faudry E, Ebel C, Attree I, Elsen S. 2009. Anti-activator ExsD forms a 1:1 complex with ExsA to inhibit transcription of type III secretion operons. J Biol Chem 284:15762-15770. http://dx.doi.org/10.1074/jbc.M109.003533.
26. Dasgupta N, Lykken GL, Wolfgang MC, Yahr TL. 2004. A novel antianti-activator mechanism regulates expression of the Pseudomonas aeruginosa type III secretion system. Mol Microbiol 53:297-308. http://dx.doi.org/10.1111/j.1365-2958.2004.04128.x.
27. Urbanowski ML, Lykken GL, Yahr TL. 2005. A secreted regulatory protein couples transcription to the secretory activity of the Pseudomonas aeruginosa type III secretion system. Proc Natl Acad Sci U S A 102:9930-9935. http://dx.doi.org/10.1073/pnas.0504405102.
28. Rietsch A, Vallet-Gely I, Dove SL, Mekalanos JJ. 2005. ExsE, a secreted regulator of type III secretion genes in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 102:8006-8011. http://dx.doi.org/10.1073/pnas.0503005102.
29. Vogelaar NJ, Jing X, Robinson HH, Schubot FD. 2010. Analysis of the crystal structure of the ExsC. ExsE complex reveals distinctive binding interactions of the Pseudomonas aeruginosa type III secretion chaperone ExsC with ExsE and ExsD. Biochemistry (Mosc) 49:5870-5879. http://dx.doi.org/10.1021/bi100432e.
30. Urbanowski ML, Brutinel ED, Yahr TL. 2007. Translocation of ExsE into Chinese hamster ovary cells is required for transcriptional induction of the Pseudomonas aeruginosa type III secretion system. Infect Immun 75:4432-4439. http://dx.doi.org/10.1128/IAI.00664-07.
31. Bowser TE, Bartlett VJ, Grier MC, Verma AK, Warchol T, Levy SB, Alekshun MN. 2007. Novel anti-infection agents: small-molecule inhibitors of bacterial transcription factors. Bioorg Med Chem Lett 17:5652-5655. http://dx.doi.org/10.1016/j.bmcl.2007.07.072.
32. Grier MC, Garrity-Ryan LK, Bartlett VJ, Klausner KA, Donovan PJ, Dudley C, Alekshun MN, Tanaka SK, Draper MP, Levy SB, Kim OK. 2010. N-Hydroxybenzimidazole inhibitors of ExsA MAR transcription factor in Pseudomonas aeruginosa: in vitro anti-virulence activity and metabolic stability. Bioorg Med Chem Lett 20:3380-3383. http://dx.doi.org/10.1016/j.bmcl.2010.04.014.
33. Kim OK, Garrity-Ryan LK, Bartlett VJ, Grier MC, Verma AK, Medjanis G, Donatelli JE, Macone AB, Tanaka SK, Levy SB, Alekshun MN. 2009. N-Hydroxybenzimidazole inhibitors of the transcription factor LcrF in Yersinia: novel antivirulence agents. J Med Chem 52:5626-5634. http://dx.doi.org/10.1021/jm9006577.
34. Gallegos MT, Schleif R, Bairoch A, Hofmann K, Ramos JL. 1997. Arac/XylS family of transcriptional regulators. Microbiol Mol Biol Rev 61:393-410.
35. Brutinel ED, Vakulskas CA, Brady KM, Yahr TL. 2008. Characterization of ExsA and of ExsA-dependent promoters required for expression of the Pseudomonas aeruginosa type III secretion system. Mol Microbiol 68:657-671. http://dx.doi.org/10.1111/j.1365-2958.2008.06179.x.
36. King JM, Schesser Bartra S, Plano G, Yahr TL. 2013. ExsA and LcrF recognize similar consensus binding sites, but differences in their oligomeric state influence interactions with promoter DNA. J Bacteriol 195:5639-5650. http://dx.doi.org/10.1128/JB.00990-13.
37. Fuchs EL, Brutinel ED, Klem ER, Fehr AR, Yahr TL, Wolfgang MC. 2010. In vitro and in vivo characterization of the Pseudomonas aeruginosa cyclic AMP (cAMP) phosphodiesterase CpdA, required for cAMP homeostasis and virulence factor regulation. J Bacteriol 192:2779-2790. http://dx.doi.org/10.1128/JB.00168-10.
38. Brutinel ED, Vakulskas CA, Yahr TL. 2009. Functional domains of ExsA, the transcriptional activator of the Pseudomonas aeruginosa type III secretion system. J Bacteriol 191:3811-3821. http://dx.doi.org/10.1128/JB.00002-09.
39. Marsden AE, Schubot FD, Yahr TL. 2014. Self-association is required for occupation of adjacent binding sites in Pseudomonas aeruginosa type III secretion system promoters. J Bacteriol 196:3546-3555. http://dx.doi.org/10.1128/JB.01969-14.
40. King JM, Brutinel ED, Marsden AE, Schubot FD, Yahr TL. 2012. Orientation of Pseudomonas aeruginosa ExsA monomers bound to promoter DNA and base-specific contacts with the PexoT promoter. J Bacteriol 194:2573-2585. http://dx.doi.org/10.1128/JB.00107-12.
41. Fuchs EL, Brutinel ED, Jones AK, Fulcher NB, Urbanowski ML, Yahr TL, Wolfgang MC. 2010. The Pseudomonas aeruginosa Vfr regulator controls global virulence factor expression through cyclic AMP-dependent and -independent mechanisms. J Bacteriol 192:3553-3564. http://dx.doi.org/10.1128/JB.00363-10.
42. Garrity-Ryan LK, Kim OK, Balada-Llasat JM, Bartlett VJ, Verma AK, Fisher ML, Castillo C, Songsungthong W, Tanaka SK, Levy SB, Mecsas J, Alekshun MN. 2010. Small molecule inhibitors of LcrF, a Yersinia pseudotuberculosis transcription factor, attenuate virulence and limit infection in a murine pneumonia model. Infect Immun 78:4683-4690. http://dx.doi.org/10.1128/IAI.01305-09.