Crystal structures of klebsiella pneumoniae dihydrofolate reductase bound to propargyl-linked antifolates reveal features for potency and selectivity

Antimicrobial Agents and Chemotherapy

Volumn 58, Issue 12, 2014, Pages 7484-7491

  Lamb, Kristen M ^a   Lombardo, Michael N ^a   Alverson, Jeremy ^b   Priestley, Nigel D ^b   Wright, Dennis L ^a   Anderson, Amy C ^a  

^a UNIVERSITY OF CONNECTICUT   (United States)

^b UNIVERSITY OF MONTANA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIHYDROFOLATE REDUCTASE; FOLIC ACID ANTAGONIST; ANTIINFECTIVE AGENT; BACTERIAL PROTEIN; RECOMBINANT PROTEIN; TRIMETHOPRIM;

ARTICLE; BACTERIAL GROWTH; BACTERIAL STRAIN; CONFORMATION; CRYSTAL STRUCTURE; CRYSTALLIZATION; DRUG POTENCY; GRAM POSITIVE BACTERIUM; GROWTH INHIBITION; KLEBSIELLA PNEUMONIAE; NONHUMAN; ANTAGONISTS AND INHIBITORS; ANTIBIOTIC RESISTANCE; CHEMISTRY; ENZYMOLOGY; ESCHERICHIA COLI; GENE EXPRESSION; GENETICS; METABOLISM; MOLECULAR DOCKING; PROTEIN DOMAIN; PROTEIN SECONDARY STRUCTURE; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; CRYSTALLOGRAPHY, X-RAY; ESCHERICHIA COLI; FOLIC ACID ANTAGONISTS; GENE EXPRESSION; KLEBSIELLA PNEUMONIAE; MOLECULAR DOCKING SIMULATION; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN STRUCTURE, SECONDARY; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAHYDROFOLATE DEHYDROGENASE; TRIMETHOPRIM; TRIMETHOPRIM RESISTANCE;

EID: 84912142088     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.03555-14     Document Type: Article

References (35)

1. Rice L. 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. Boucher H, Talbot G, Bradley J, Edwards J, Gilbert D, Rice L, 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.
3. Meatherall B, Gregson D, Ross T, Pitout J, Laupland K. 2009. Incidence, risk factors, and outcomes of Klebsiella pneumoniae bacteremia. Am. J. Med. 122:866-873. http://dx.doi.org/10.1016/j.amjmed.2009.03.034.
4. Tsay R, Siu L, Fung C, Chang F. 2002. Characteristics of bacteremia between community-acquired and nosocomial Klebsiella pneumoniae infection: risk factor for mortality and the impact of capsular serotypes as a herald for community-acquired infection. Arch. Intern. Med. 162:1021-1027. http://dx.doi.org/10.1001/archinte.162.9.1021.
5. Peleg A, Hooper D. 2010. Hospital-acquired infections due to gramnegative bacteria. N. Engl. J. Med. 362:1804-1813. http://dx.doi.org/10 .1056/NEJMra0904124.
6. Yigit H, Queenan A, Anderson G, Domenech-Sanchez A, Biddle J, Steward C, Alberti S, Bush K, Tenover F. 2001. Novel carbapenemhydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob. Agents Chemother. 45:1151-1161. http://dx.doi.org/10.1128/AAC.45.4.1151-1161.2001.
7. Bradford PA, Bratu S, Urban C, Visalli M, Mariano N, Landman D, Rahal JJ, Brooks S, Cebular S, Quale J. 2004. Emergence of carbapenemresistant Klebsiella species possessing the class A carbapenem-hydrolyzing KPC-2 and inhibitor-resistant TEM-30 beta-lactamases in New York City. Clin. Infect. Dis. 39:55-60. http://dx.doi.org/10.1086/421495.
8. Bush K. 2010. Alarming -lactamase-mediated resistance in multidrugresistant Enterobacteriaceae. Curr. Opin. Microbiol. 13:558-564. http://dx .doi.org/10.1016/j.mib.2010.09.006.
9. Souli M, Galani I, Giamarellou H. 2009. Emergence of extensively drugresistant and pandrug-resistant Gram-negative bacilli in Europe. Euro Surveill. 13(47):pii 19045. http://www.eurosurveillance.org/ViewArticle .aspx?ArticleId 19045.
10. European Centre for Disease Prevention and Control. 2012. Antimicrobial resistance surveillance in Europe 2011. Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). European Centre for Disease Prevention and Control, Stockholm, Sweden.
11. Ho J, Tambyah P, Paterson D. 2010. Multiresistant Gram-negative infections: a global perspective. Curr. Opin. Infect. Dis. 23:546-553. http: //dx.doi.org/10.1097/QCO.0b013e32833f0d3e.
12. Hawser S, Lociuro S, Islam K. 2006. Dihydrofolate reductase inhibitors as antibacterial agents. Biochem. Pharmacol. 71:941-948. http://dx.doi.org/10 .1016/j.bcp.2005.10.052.
13. Purcell W, Ettinger D. 2003. Novel antifolate drugs. Curr. Oncol. Rep. 5:114-125. http://dx.doi.org/10.1007/s11912-003-0098-3.
14. Wright D, Anderson A. 2011. Antifolate agents: a patent review (2006-2010). Expert Opin. Ther. Pat. 21:1293-1308. http://dx.doi.org/10.1517 /13543776.2011.587804.
15. Hooton T. 2003. The current management strategies for communityacquired urinary tract infection. Infect. Dis. Clin. North Am. 17:303-332. http://dx.doi.org/10.1016/S0891-5520(03)00004-7.
16. Zhanel G, Karlowsky J, Harding G, Carrie A, Mazzulli T, Low D, The Canadian Urinary Isolate Study Group, Hoban D. 2000. A Canadian national surveillance study of urinary tract isolates from outpatients: comparison of the activities of trimethoprim-sulfamethoxazole, ampicillin, mecillinam, nitrofurantoin, and ciprofloxacin. Antimicrob. Agents Chemother. 44: 1089 -1092. http://dx.doi.org/10.1128/AAC.44 .4.1089-1092.2000.
17. Garcia Garcia M, Munoz Bellido J, Garcia Rodriguez J, Spanish Cooperative Group for the Study of Antimicrobial Susceptibility of Community Uropathogens. 2007. In vitro susceptibility of communityacquired urinary tract pathogens to commonly used antimicrobial agents in Spain: a comparative multicenter study (2002-2004). J. Chemother. 19:263-270. http://dx.doi.org/10.1179/joc.2007.19.3.263.
18. Blahna M, Zalewski C, Reuer J, Kahlmeter G, Foxman B, Marrs C. 2006. The role of horizontal gene transfer in the spread of trimethoprimsulfamethoxazole resistance among uropathogenic Escherichia coli in Europe and Canada. J. Antimicrob. Chemother. 57:666-672. http://dx.doi .org/10.1093/jac/dkl020.
19. Brolund A, Sundqvist M, Kahlmeter G, Grape M. 2010. Molecular characterisation of trimethoprim resistance in Escherichia coli and Klebsiella pneumoniae during a two-year intervention on trimethoprim use. PLoS One 5:e9233. http://dx.doi.org/10.1371/journal.pone.0009233.
20. Seputiene V, Povilonis J, Ruzauskas M, Pavilonis A, Suziedeliene E. 2010. Prevalence of trimethoprim resistance genes in Escherichia coli isolates of human and animal origin in Lithuania. J. Med. Microbiol. 59:315-322. http://dx.doi.org/10.1099/jmm.0.015008-0.
21. Bolstad D, Bolstad E, Frey K, Wright D, Anderson A. 2008. A structurebased approach to the development of potent and selective inhibitors of dihydrofolate reductase from Cryptosporidium. J. Med. Chem. 51:6839-6852. http://dx.doi.org/10.1021/jm8009124.
22. Liu J, Bolstad D, Smith A, Priestley N, Wright D, Anderson A. 2008. Structure-guided development of efficacious antifungal agents targeting Candida glabrata dihydrofolate reductase. Chem. Biol. 15:990-996. http: //dx.doi.org/10.1016/j.chembiol.2008.07.013.
23. Beierlein J, Frey K, Bolstad D, Pelphrey P, Joska T, Smith A, Priestley N, Wright D, Anderson A. 2008. Synthetic and crystallographic studies of a new inhibitor series targeting Bacillus anthracis dihydrofolate reductase. J. Med. Chem. 51:7532-7540. http://dx.doi.org /10.1021/jm800776a.
24. Frey K, Liu J, Lombardo M, Bolstad D, Wright D, Anderson A. 2009. Crystal structures of wild-type and mutant methicillin-resistant Staphylococcus aureus dihydrofolate reductase reveal an alternative conformation of NADPH that may be linked to trimethoprim resistance. J. Mol. Biol. 387:1298-1308. http://dx.doi.org/10.1016/j.jmb.2009.02.045.
25. Viswanathan K, Frey K, Scocchera E, Martin B, Swain P, Alverson J, Priestley N, Anderson A, Wright D. 2012. Toward new therapeutics for skin and soft tissue infections: propargyl-linked antifolates are potent inhibitors of MRSA and Streptococcus pyogenes. PLoS One 7:e29434. http: //dx.doi.org/10.1371/journal.pone.0029434.
26. Lamb K, G-Dayanandan N, Wright D, Anderson A. 2013. Elucidating features that drive the design of selective antifolates using crystal structures of human dihydrofolate reductase. Biochemistry 52:7318-7326. http://dx.doi.org/10.1021/bi400852h.
27. Adams P, Afonine P, Bunkóczi G, Chen V, Davis I, Echools N, Headd J, Hung L-W, Kapral G, Grosse-Kunstleve R, McCoy A, Moriarty N, Oeffner R, Read R, Richardson D, Richardson J, Terwilliger T, Zwart P. 2010. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66:213-221. http://dx.doi.org/10.1107/S0907444909052925.
28. Dunbar J, Yennawar H, Banerjee S, Luo J, Farber G. 1997. The effects of denaturants on protein structure. Protein Sci. 6:1727-1733. http://dx.doi .org/10.1002/pro.5560060813.
29. Schüttelkopf A, van Aalten D. 2004. PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr. D Biol. Crystallogr. 60:1355-1363. http://dx.doi.org/10.1107/S0907444904011679.
30. Emsley P, Cowtan K. 2004. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60:2126-2132. http://dx .doi.org/10.1107/S0907444904019158.
31. Frey K, Lombardo M, Wright D, Anderson A. 2010. Towards the understanding of resistance mechanisms in clinically isolated trim-ethoprim-resistant, methicillin-resistant Staphylococcus aureus dihydrofolate reductase. J. Struct. Biol. 170:93-97. http://dx.doi.org/10.1016/j.jsb .2009.12.011.
32. Frey K, Viswanathan K, Wright D, Anderson A. 2012. Prospectively screening novel antibacterial inhibitors of dihydrofolate reductase for mutational resistance. Antimicrob. Agents Chemother. 56:3556-3562. http: //dx.doi.org/10.1128/AAC.06263-11.
33. Bolin J, Filman D, Matthews D, Hamlin R, Kraut J. 1982. Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 A resolution. I. General features and binding of methotrexate. J. Biol. Chem. 257:13650-13662.
34. Zhou W, Scocchera E, Wright D, Anderson A. 2013. Antifolates as effective antimicrobial agents: new generations of trimethoprim analogs. Med. Chem. Comm. 4:908 -915. http://dx.doi.org/10.1039 /c3md00104k.
35. Paulsen J, Viswanathan K, Wright D, Anderson A. 2013. Structural analysis of the active sites of dihydrofolate reductase from two species of Candida uncovers ligand-induced conformational changes shared among species. Bioorg. Med. Chem. Lett. 23:1279-1284. http://dx.doi.org/10 .1016/j.bmcl.2013.01.008.