Structural/mechanistic insights into the efficacy of nonclassical β-lactamase inhibitors against extensively drug resistant Stenotrophomonas maltophilia clinical isolates

Molecular Microbiology

Volumn 106, Issue 3, 2017, Pages 492-504

  Calvopiña, Karina ^a   Hinchliffe, Philip ^a   Brem, Jürgen ^b   Heesom, Kate J ^a   Johnson, Samar ^a   Cain, Ricky ^c   Lohans, Christopher T ^b   Fishwick, Colin W G ^c   Schofield, Christopher J ^b   Spencer, James ^a   Avison, Matthew B ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c UNIVERSITY OF LEEDS   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AVIBACTAM; AVIBACTAM PLUS CEFTAZIDIME; AZTREONAM; BETA LACTAMASE; BORONIC ACID DERIVATIVE; CEFTAZIDIME; CLAVULANIC ACID; MEROPENEM; SERINE; ANTIINFECTIVE AGENT; AZABICYCLO DERIVATIVE; BACTERIAL PROTEIN; BETA LACTAMASE INHIBITOR;

ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIUM ISOLATE; BINDING AFFINITY; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFICACY; DRUG HYDROLYSIS; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME INHIBITION; HYDROPHOBICITY; IC50; MINIMUM INHIBITORY CONCENTRATION; MUTANT; NONHUMAN; NUCLEOPHILICITY; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEOMICS; STENOTROPHOMONAS MALTOPHILIA; X RAY CRYSTALLOGRAPHY; CHEMISTRY; GENETICS; METABOLISM; MICROBIAL SENSITIVITY TEST; PROCEDURES;

ANTI-BACTERIAL AGENTS; AZABICYCLO COMPOUNDS; AZTREONAM; BACTERIAL PROTEINS; BETA-LACTAMASE INHIBITORS; BETA-LACTAMASES; CEFTAZIDIME; CRYSTALLOGRAPHY, X-RAY; DRUG RESISTANCE, BACTERIAL; MICROBIAL SENSITIVITY TESTS; STENOTROPHOMONAS MALTOPHILIA;

EID: 85032861340     PISSN: 0950382X     EISSN: 13652958     Source Type: Journal    
DOI: 10.1111/mmi.13831     Document Type: Article

References (70)

1. Abboud, M.I., Damblon, C., Brem, J., Smargiasso, N., Mercuri, P., Gilbert, B., et al. (2016) Interaction of Avibactam With Class B metallo-beta-lactamases. Antimicrob Agents Chemother 60: 5655–5662.
2. Adams, P.D., Afonine, P.V., Bunkoczi, G., Chen, V.B., Davis, I.W., Echols, N., et al. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr Sect D 66: 213–221.
3. Al Roomi, L.G., Sutton, A.M., Cockburn, F., and McAllister, T.A. (1984) Amoxycillin and clavulanic acid in the treatment of urinary infection. Arch Dis Child 59: 256–259.
4. Alonso, A., and Martinez, J.L. (2000) Cloning and characterization of SmeDEF, a novel multidrug efflux pump from Stenotrophomonas maltophilia. Antimicrob Agents Chemother 44: 3079–3086.
5. Ambler, R.P. (1980) The Structure of β-Lactamases. Philos Trans R Soc Lond B Biol Sci 289: 321.
6. van Berkel, S.S., Brem, J., Rydzik, A.M., Salimraj, R., Cain, R., Verma, A., et al. (2013) Assay platform for clinically relevant metallo-β-lactamases. J Med Chem 56: 6945–6953.
7. Blizzard, T.A., Chen, H., Kim, S., Wu, J., Bodner, R., Gude, C., et al. (2014) Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®. Bioorg Med Chem Lett 24: 780–785.
8. Brem, J., Cain, R., Cahill, S., McDonough, M.A., Clifton, I.J., Jimenez-Castellanos, J.C., et al. (2016) Structural basis of metallo-beta-lactamase, serine-beta-lactamase and penicillin-binding protein inhibition by cyclic boronates. Nat Commun 7: 12406.
9. Brooke, J.S. (2012) Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clin Microbiol Rev 25: 2–41.
10. Burns, C.J.R., Goswami, R.W., Jackson, T., Lessen, W., Li, D., Pevear, P.K., et al. (2010) Beta-lactamase inhibitors. Google Patents. [WWW document]. https://www.google.com/patents/WO2010056827A1?cl=en
11. Bush, K. (2013) The ABCD's of β-lactamase nomenclature. J Infect Chemother 19: 549–559.
12. Cahill, S.T., Cain, R., Wang, D.Y., Lohans, C.T., Wareham, D.W., Oswin, H., et al. (2017) Cyclic boronates inhibit all classes of beta-lactamase. Antimicrob Agents Chemother. 61. pii: e02260-16. doi: 10.1128/AAC.02260-16.
13. Calvopina, K., Umland, K.D., Rydzik, A.M., Hinchliffe, P., Brem, J., Spencer, J., et al. (2016) Sideromimic Modification of Lactivicin Dramatically Increases Potency against Extensively Drug-Resistant Stenotrophomonas maltophilia Clinical Isolates. Antimicrob Agents Chemother 60: 4170–4175.
14. Chen, V.B., Arendall, W.B., III, Headd, J.J., Keedy, D.A., Immormino, R.M., Kapral, G.J., et al. (2010) MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr Sect D 66: 12–21.
15. Choi, H., Paton, R.S., Park, H., and Schofield, C.J. (2016) Investigations on recyclisation and hydrolysis in avibactam mediated serine β-lactamase inhibition. Org Biomol Chem 14: 4116–4128.
16. ClinicalTrials.gov (2016) VNRX-5133-101/102: a randomized, double blind, placebo-controlled, sequential group, dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics of single and repeat doses of VNRX-5133 in healthy adult volunteers. [WWW document]. https://clinicaltrials.gov/ct2/show/NCT02955459
17. CLSI (2015) Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement. Wayne, PA: Clinical and Laboratory Standards Institute CLSI document M100-S25.
18. Coleman, K. (2011) Diazabicyclooctanes (DBOs): a potent new class of non-β-lactam β-lactamase inhibitors. Curr Opin Microbiol 14: 550–555.
19. Crossman, L.C., Gould, V.C., Dow, J.M., Vernikos, G.S., Okazaki, A., Sebaihia, M., et al. (2008) The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants. Genome Biol 9: R74–R74.
20. Drawz, S.M., and Bonomo, R.A. (2010) Three decades of β-lactamase inhibitors. Clin Microbiol Rev 23: 160–201.
21. Drawz, S.M., Papp-Wallace, K.M., and Bonomo, R.A. (2014) New beta-lactamase inhibitors: a therapeutic renaissance in an MDR world. Antimicrob Agents Chemother 58: 1835–1846.
22. Ehmann, D.E., Jahić, H., Ross, P.L., Gu, R.-F., Hu, J., Kern, G., et al. (2012) Avibactam is a covalent, reversible, non–β-lactam β-lactamase inhibitor. Proc Natl Acad Sci USA 109: 11663–11668.
23. Emsley, P., Lohkamp, B., Scott, W.G., and Cowtan, K. (2010) Features and development of Coot. Acta Crystallogr Sect D 66: 486–501.
24. Fass, R.J., and Prior, R.B. (1989) Comparative in vitro activities of piperacillin-tazobactam and ticarcillin-clavulanate. Antimicrob Agents Chemother 33: 1268–1274.
25. Finlay, J., Miller, L., and Poupard, J.A. (2003) A review of the antimicrobial activity of clavulanate. J Antimicrob Chemother 52: 18–23.
26. Fonseca, F., Chudyk, E.I., van der Kamp, M.W., Correia, A., Mulholland, A.J., and Spencer, J. (2012) The basis for carbapenem hydrolysis by class A β-lactamases: a combined investigation using crystallography and simulations. J Am Chem Soc 134: 18275–18285.
27. Garcia-Leon, G., Puig, C.R.D., de la Fuente, C.G., Martinez-Martinez, L., Martinez, J.L., and Sanchez, M.B. (2015) High-level quinolone resistance is associated with the overexpression of smeVWX in Stenotrophomonas maltophilia clinical isolates. Clin Microbiol Infect 21: 464–467.
28. Gorrec, F. (2009) The MORPHEUS protein crystallization screen. J Appl Crystallogr 42: 1035–1042.
29. Gould, V.C., and Avison, M.B. (2006) SmeDEF-mediated antimicrobial drug resistance in Stenotrophomonas maltophilia clinical isolates having defined phylogenetic relationships. J Antimicrob Chemother 57: 1070–1076.
30. Gould, V.C., Okazaki, A., and Avison, M.B. (2006) Beta-lactam resistance and beta-lactamase expression in clinical Stenotrophomonas maltophilia isolates having defined phylogenetic relationships. J Antimicrob Chemother 57: 199–203.
31. Gould, V.C., Okazaki, A., and Avison, M.B. (2013) Coordinate hyperproduction of SmeZ and SmeJK efflux pumps extends drug resistance in Stenotrophomonas maltophilia. Antimicrob Agents Chemother 57: 655–657.
32. Hamad, B. (2010) The antibiotics market. Nat Rev Drug Discov 9: 675–676.
33. Hanes, M.S., Jude, K.M., Berger, J.M., Bonomo, R.A., and Handel, T.M. (2009) Structural and biochemical characterization of the interaction between KPC-2 β-lactamase and β-lactamase inhibitor protein. Biochemistry 48: 9185–9193.
34. Hecker, S.J., Reddy, K.R., Totrov, M., Hirst, G.C., Lomovskaya, O., Griffith, D.C., et al. (2015) Discovery of a cyclic boronic acid β-lactamase inhibitor (RPX7009) with utility vs class A serine carbapenemases. J Med Chem 58: 3682–3692.
35. Huang, Y.W., Lin, C.W., Ning, H.C., Lin, Y.T., Chang, Y.C., and Yang, T.C. (2017) Overexpression of SmeDEF efflux pump decreases aminoglycoside resistance in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 61. pii: e02685-16. doi: 10.1128/AAC.02685-16
36. Jacobs, C., Huang, L.J., Bartowsky, E., Normark, S., and Park, J.T. (1994) Bacterial cell wall recycling provides cytosolic muropeptides as effectors for beta-lactamase induction. EMBO J 13: 4684–4694.
37. Jacobs, C., Frère, J.-M., and Normark, S. (1997) Cytosolic intermediates for cell wall biosynthesis and degradation control inducible β-lactam resistance in gram-negative bacteria. Cell 88: 823–832.
38. Kabsch, W. (2010) XDS. Acta Crystallogr Sect D 66: 125–132.
39. King, A.M., King, D.T., French, S., Brouillette, E., Asli, A., Alexander, J.A.N., et al. (2016) Structural and kinetic characterization of diazabicyclooctanes as dual inhibitors of both serine-β-lactamases and penicillin-binding proteins. ACS Chem Biol 11: 864–868.
40. King, D.T., King, A.M., Lal, S.M., Wright, G.D., and Strynadka, N.C.J. (2015) Molecular mechanism of avibactam-mediated beta-lactamase inhibition. ACS Infect Dis 1: 175–184.
41. Krishnan, N.P., Nguyen, N.Q., Papp-Wallace, K.M., Bonomo, R.A., and van den Akker, F. (2015) Inhibition of Klebsiella beta-Lactamases (SHV-1 and KPC-2) by avibactam: a structural study. PLoS One 10: e0136813. doi: 10.1371/journal.pone.0136813
42. Lahiri, S.D., Mangani, S., Durand-Reville, T., Benvenuti, M., De Luca, F., Sanyal, G., and Docquier, J.D. (2013) Structural insight into potent broad-spectrum inhibition with reversible recyclization mechanism: avibactam in complex with CTX-M-15 and Pseudomonas aeruginosa AmpC beta-lactamases. Antimicrob Agents Chemother 57: 2496–2505.
43. Lahiri, S.D., Johnstone, M.R., Ross, P.L., McLaughlin, R.E., Olivier, N.B., and Alm, R.A. (2014) Avibactam and class C beta-lactamases: mechanism of inhibition, conservation of the binding pocket, and implications for resistance. Antimicrob Agents Chemother 58: 5704–5713.
44. Lahiri, S.D., Mangani, S., Jahic, H., Benvenuti, M., Durand-Reville, T.F., De Luca, F., et al. (2015) Molecular basis of selective inhibition and slow reversibility of avibactam against class D carbapenemases: a structure-guided study of OXA-24 and OXA-48. ACS Chem Biol 10: 591–600.
45. Lemmen, S.W., Häfner, H., Reinert, R.R., Zolldann, D., Kümmerer, K., and Lütticken, R. (2001) Comparison of serum bactericidal activity of ceftazidime, ciprofloxacin and meropenem against Stenotrophomonas maltophilia. J Antimicrob Chemother 47: 118–120.
46. Looney, W.J., Narita, M., and Muhlemann, K. (2009) Stenotrophomonas maltophilia: an emerging opportunist human pathogen. Lancet Infect Dis 9: 312–323.
47. Marshall, S., Hujer, A.M., Rojas, L.J., Papp-Wallace, K.M., Humphries, R.M., Spellberg, B., et al. (2017) Can ceftazidime-avibactam and aztreonam overcome beta-lactam resistance conferred by metallo-beta-lactamases in enterobacteriaceae? Antimicrob Agents Chemother 61. pii: e02243-16. doi: 10.1128/AAC.02243-16
48. McCoy, A.J., Grosse-Kunstleve, R.W., Adams, P.D., Winn, M.D., Storoni, L.C., and Read, R.J. (2007) Phaser crystallographic software. J Appl Crystallogr 40: 658–674.
49. Meroueh, S.O., Fisher, J.F., Schlegel, H.B., and Mobashery, S. (2005) Ab initio QM/MM study of class A β-lactamase acylation: dual participation of Glu166 and Lys73 in a concerted base promotion of Ser70. J Am Chem Soc 127: 15397–15407.
50. Mojica, M.F., Ouellette, C.P., Leber, A., Becknell, M.B., Ardura, M.I., Perez, F., et al. (2016) Successful treatment of bloodstream infection due to metallo-β-lactamase-producing Stenotrophomonas maltophilia in a renal transplant patient. Antimicrob Agents Chemother 60: 5130–5134.
51. Moriarty, N.W., Grosse-Kunstleve, R.W., and Adams, P.D. (2009) Electronic ligand builder and optimization workbench (eLBOW): a tool for ligand coordinate and restraint generation. Acta Crystallogr Sect D 65: 1074–1080.
52. Okazaki, A., and Avison, M.B. (2008) Induction of L1 and L2 beta-lactamase production in Stenotrophomonas maltophilia is dependent on an AmpR-type regulator. Antimicrob Agents Chemother 52: 1525–1528.
53. Reading, C., and Cole, M. (1977) Clavulanic acid: a beta-lactamase-inhibiting beta-lactam from Streptomyces clavuligerus. Antimicrob Agents Chemother 11: 852–857.
54. Ryan, R.P., Monchy, S., Cardinale, M., Taghavi, S., Crossman, L., Avison, M.B., et al. (2009) The versatility and adaptation of bacteria from the genus Stenotrophomonas. Nat Rev Microbiol 7: 514–525.
55. Silva, J.C., Gorenstein, M.V., Li, G.Z., Vissers, J.P., and Geromanos, S.J. (2006) Absolute quantification of proteins by LCMSE: a virtue of parallel MS acquisition. Mol Cell Proteomics 5: 144–156.
56. Stachyra, T., Levasseur, P., Péchereau, M.-C., Girard, A.-M., Claudon, M., Miossec, C., and Black, M.T. (2009) In vitro activity of the β-lactamase inhibitor NXL104 against KPC-2 carbapenemase and Enterobacteriaceae expressing KPC carbapenemases. J Antimicrob Chemother 64: 326–329.
57. Stachyra, T., Pechereau, M.C., Bruneau, J.M., Claudon, M., Frere, J.M., Miossec, C., et al. (2010) Mechanistic studies of the inactivation of TEM-1 and P99 by NXL104, a novel non-beta-lactam beta-lactamase inhibitor. Antimicrob Agents Chemother 54: 5132–5138.
58. Strynadka, N.C.J., Adachi, H., Jensen, S.E., Johns, K., Sielecki, A., Betzel, C., et al. (1992) Molecular structure of the acyl-enzyme intermediate in [beta]-lactam hydrolysis at 1.7 A resolution. Nature 359: 700–705.
59. Sulton, D., Pagan-Rodriguez, D., Zhou, X., Liu, Y.D., Hujer, A.M., Bethel, C.R., et al. (2005) Clavulanic acid inactivation of SHV-1 and the inhibitor-resistant S130G SHV-1 beta-lactamase—insights into the mechanism of inhibition. J Biol Chem 280: 35528–35536.
60. Talfan, A., Mounsey, O., Charman, M., Townsend, E., and Avison, M.B. (2013) Involvement of mutation in ampD I, mrcA, and at least one additional gene in beta-lactamase hyperproduction in Stenotrophomonas maltophilia. Antimicrob Agents Chemother 57: 5486–5491.
61. Van Boeckel, T.P., Gandra, S., Ashok, A., Caudron, Q., Grenfell, B.T., Levin, S.A., and Laxminarayan, R. (2014) Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis 14: 742–750.
62. Vandavasi, V.G., Weiss, K.L., Cooper, J.B., Erskine, P.T., Tomanicek, S.J., Ostermann, A., et al. (2016) Exploring the mechanism of β-lactam ring protonation in the class A β-lactamase acylation mechanism using neutron and x-ray crystallography. J Med Chem 59: 474–479.
63. Versporten, A., Bolokhovets, G., Ghazaryan, L., Abilova, V., Pyshnik, G., Spasojevic, T., et al. (2014) Antibiotic use in eastern Europe: a cross-national database study in coordination with the WHO Regional Office for Europe. Lancet Infect Dis 14: 381–387.
64. de Vrankrijker, A.M.M., Wolfs, T.F.W., and van der Ent, C.K. (2010) Challenging and emerging pathogens in cystic fibrosis. Paediatr Respir Rev 11: 246–254.
65. Walsh, T.R., Hall, L., Assinder, S.J., Nichols, W.W., Cartwright, S.J., Macgowan, A.P., and Bennett, P.M. (1994) Sequence-Analysis of the L1 Metallo-Beta-Lactamase from Xanthomonas maltophilia. Biochim Biophys Acta 1218: 199–201.
66. Walsh, T.R., MacGowan, A.P., and Bennett, P.M. (1997) Sequence analysis and enzyme kinetics of the L2 serine beta-lactamase from Stenotrophomonas maltophilia. Antimicrob Agents Chemother 41: 1460–1464.
67. Wang, D.Y., Abboud, M.I., Markoulides, M.S., Brem, J., and Schofield, C.J. (2016) The road to avibactam: the first clinically useful non-beta-lactam working somewhat like a beta-lactam. Future Med Chem 8: 1063–1084.
68. Waterman, D.G., Winter, G., Gildea, R.J., Parkhurst, J.M., Brewster, A.S., Sauter, N.K., and Evans, G. (2016) Diffraction-geometry refinement in the DIALS framework. Acta Crystallogr Sect D 72: 558–575.
69. Winn, M.D., Ballard, C.C., Cowtan, K.D., Dodson, E.J., Emsley, P., Evans, P.R., et al. (2011) Overview of the CCP4 suite and current developments. Acta Crystallogr Sect D Biol Crystallogr 67: 235–242.
70. Xu, H., Hazra, S., and Blanchard, J.S. (2012) NXL104 irreversibly inhibits the beta-lactamase from Mycobacterium tuberculosis. Biochemistry 51: 4551–4557.