Hybrid Antibiotic Overcomes Resistance in P. aeruginosa by Enhancing Outer Membrane Penetration and Reducing Efflux

Journal of Medicinal Chemistry

Volumn 59, Issue 18, 2016, Pages 8441-8455

  Gorityala, Bala Kishan ^a   Guchhait, Goutam ^a   Goswami, Sudeep ^a   Fernando, Dinesh M ^a   Kumar, Ayush ^a   Zhanel, George G ^a   Schweizer, Frank ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

MOXIFLOXACIN; TOBRAMYCIN; ANTIINFECTIVE AGENT; QUINOLONE DERIVATIVE;

ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL MEMBRANE; BACTERIUM ISOLATE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG PENETRATION; GALLERIA MELLONELLA; HYBRID; LARVA; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; OUTER MEMBRANE; PROTON MOTIVE FORCE; PSEUDOMONAS AERUGINOSA; ANALOGS AND DERIVATIVES; CHEMISTRY; CYTOLOGY; DRUG EFFECTS; HUMAN; MULTIDRUG RESISTANCE; PSEUDOMONAS INFECTIONS;

ANTI-BACTERIAL AGENTS; DRUG RESISTANCE, MULTIPLE, BACTERIAL; FLUOROQUINOLONES; HUMANS; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS INFECTIONS; TOBRAMYCIN;

EID: 84988701271     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.6b00867     Document Type: Article

References (49)

1. Rice, L. B. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: NO ESKAPE J. Infect. Dis. 2008, 197, 1079-1081 10.1086/533452
2. Peleg, A. Y.; Hooper, D. C. Hospital-acquired infections due to gram-negative bacteria N. Engl. J. Med. 2010, 362, 1804-1813 10.1056/NEJMra0904124
3. Wisplinghoff, H.; Bischoff, S. M.; Tallent, S. M.; Seifert, H.; Wenzel, R. P.; Edmond, M. B. Nosocomial bloodstream infections in US hospitals: analysis of 24, 179 cases from a prospective nationwide surveillance study Clin. Infect. Dis. 2004, 39, 309-317 10.1086/421946
4. Weinstein, R. A.; Gaynes, R.; Edwards, J. R. Overview of nosocomial infections caused by Gram-negative bacilli Clin. Infect. Dis. 2005, 41, 848-854 10.1086/432803
5. Hidron, A. L.; Edwards, J. R.; Patel, J.; Horan, T. C.; Sievert, D. M.; Pollock, D. A.; Fridkin, S. K. 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. Epidemol. 2008, 29, 996-1011 10.1086/591861
6. Boucher, H. W.; Talbot, G. H.; Bradley, J. S.; Edwards, J. E.; Gilbert, D.; Rice, L. B.; Scheld, M.; Spellberg, B.; Bartlett, J. Bad bugs, no drugs; no ESKAPE! An update from the Infectious Diseases Society of America Clin. Infect. Dis. 2009, 48, 1-12 10.1086/595011
7. Breidenstein, E. B. M.; de laFuente-Núñez, C.; Hancock, R. E. W. Pseudomonas aeruginosa: all roads lead to resistance Trends Microbiol. 2011, 19, 419-426 10.1016/j.tim.2011.04.005
8. Nikaido, H. Prevention of drug access to bacterial targets: permeability barriers and active efflux Science 1994, 264, 382-388 10.1126/science.8153625
9. Wagner, S.; Sommer, R.; Hinsberger, S.; Lu, C.; Hartmann, R. W.; Empting, M.; Titz, A. Novel strategies for the treatment of Pseudomonas aeruginosa infections J. Med. Chem. 2016, 59, 5929-5969 10.1021/acs.jmedchem.5b01698
10. Kalan, L.; Wright, G. D. Antibiotic adjuvants: multicomponent anti-infective strategies Expert Rev. Mol. Med. 2011, 13, e5 10.1017/S1462399410001766
11. Gill, E. E.; Franco, L.; Hancock, R. E. Antibiotic adjuvants: diverse strategies for controlling drug-resistance pathogens Chem. Biol. Drug Des. 2015, 85, 56-78 10.1111/cbdd.12478
12. Hurdle, J. G.; O'Neill, A. J.; Chopra, I.; Lee, R. E. Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections Nat. Rev. Microbiol. 2011, 9, 62-75 10.1038/nrmicro2474
13. Brötz-Osterhelt, H.; Brunner, N. A. How many modes of action should an antibiotic have? Curr. Opin. Pharmacol. 2008, 8, 564-573 10.1016/j.coph.2008.06.008
14. Zhanel, G. G.; Calic, D.; Schweizer, F.; Zelenitsky, S.; Adam, H.; Lagacé-Wiens, P. R.; Rubinstein, E.; Gin, A. S.; Hoban, D. J.; Karlowsky, J. A. New lipoglycopeptides: a comparative review of dalbavancin, oritavancin and telavancin Drugs 2010, 70, 859-886 10.2165/11534440-000000000-00000
15. Pokrovskaya, V.; Baasov, T. Dual-acting hybrid antibiotics: a promising strategy to combat bacterial resistance Expert Opin. Drug Discovery 2010, 5, 883-902 10.1517/17460441.2010.508069
16. Pokrovskaya, V.; Belakhov, V.; Hainrichson, M.; Yaron, S.; Baasov, T. Design, synthesis, and evaluation of novel fluoroquinolone-aminoglycoside hybrid antibiotics J. Med. Chem. 2009, 52, 2243-2254 10.1021/jm900028n
17. Brown, E. D.; Wright, G. D. Antibacterial drug discovery on the resistance era Nature 2016, 529, 336-343 10.1038/nature17042
18. Gorityala, B. K.; Guchhait, G.; Fernando, D. M.; Deo, S.; McKenna, S. A.; Zhanel, G. G.; Kumar, A.; Schweizer, F. Adjuvants based on hybrid antibiotics overcome resistance in Pseudomonas aeruginosa and enhance fluoroquinolone efficacy Angew. Chem., Int. Ed. 2016, 55, 555-559 10.1002/anie.201508330
19. Hanessian, S.; Tremblay, M.; Swayze, E. E. Tobramycin analogues with C-5 aminoalkyl ether chains intended to mimic rings III and IV of paromomycin Tetrahedron 2003, 59, 983-993 10.1016/S0040-4020(02)01624-1
20. Guchhait, G.; Altieri, A.; Gorityala, B. K.; Yang, X.; Findlay, B.; Zhanel, G. G.; Mookherjee, N.; Schweizer, F. Amphiphilic tobramycins with immunomodulatory properties Angew. Chem., Int. Ed. 2015, 54, 6278-6282 10.1002/anie.201500598
21. Li, Q.; Xing, J.; Cheng, H.; Wang, H.; Wang, J.; Wang, S.; Zhou, J.; Zhang, H. Design, synthesis, antibacterial evaluation and docking study of novel 2-hydroxy-3-(nitroimidazolyl)-propyl-derived quinolone Chem. Biol. Drug Des. 2015, 85, 79-90 10.1111/cbdd.12395
22. Alper, P. B.; Hendrix, M.; Sears, P.; Wong, C.-H. Probing the specificity of aminoglycoside-Ribosomal RNA interactions with designed synthetic analogs J. Am. Chem. Soc. 1998, 120, 1965-1978 10.1021/ja972599h
23. Evans, M. E. Methyl 4,6-O-benzylidene-α- and -β-D-glucosides Carbohydr. Res. 1972, 21, 473-475 10.1016/S0008-6215(00)84931-9
24. Takaku, T.; Kamaike, K. Synthesis of oligoribonucleotides using 4-methoxybenzyl group as a new protecting group of the 2′-hydroxyl group of adenosine Chem. Lett. 1982, 11, 189-192 10.1246/cl.1982.189
25. 18F]Fluoroalkylated Ciprofloxacin as a Potential Bacterial Infection Imaging Agent for PET Study Bioconjugate Chem. 2010, 21, 2282-2288 10.1021/bc1002983
26. Staudinger, H.; Meyer, J. Über neue organische Phosphorverbindungen III. Phosphinmethylenderivate und Phosphinimine Helv. Chim. Acta 1919, 2, 635-646 10.1002/hlca.19190020164
27. Cunico, R. F.; Bedell, L. The triisopropylsilyl group as a hydroxyl-protecting function J. Org. Chem. 1980, 45, 4797-4798 10.1021/jo01311a058
28. Aizpurua, J. M.; Cossio, F. P.; Palomo, C. Reaction of hindered trialkylsilyl esters and trialkylsilyl ethers with triphenylphosphine dibromide: preparation of carboxylic acid bromides and alkyl bromides under mild neutral conditions J. Org. Chem. 1986, 51, 4941-4943 10.1021/jo00375a034
29. Werz, D. B.; Seeberger, P. H. Total Synthesis of Antigen Bacillus Anthracis Tetrasaccharide-Creation of an Anthrax Vaccine Candidate Angew. Chem., Int. Ed. 2005, 44, 6315-6318 10.1002/anie.200502615
30. Hill, L.; Veli, N.; Coote, P. J. Evaluation of Galleria mellonella larvae for measuring the efficacy and pharmacokinetics of antibiotic therapies against Pseudomonas aeruginosa infection Int. J. Antimicrob. Agents 2014, 43, 254-261 10.1016/j.ijantimicag.2013.11.001
31. Krezdorn, J.; Adams, S.; Coote, P. J. A Galleria mellonella infection model reveals double and triple antibiotic combination therapies with enhanced efficacy versus a multidrug-resistant strain of Pseudomonas aeruginosa J. Med. Microbiol. 2014, 63, 945-955 10.1099/jmm.0.074245-0
32. Gooderham, W. J.; Bains, M.; McPhee, J. B.; Wiegand, I.; Hancock, R. E. Induction by cationic antimicrobial peptides and involvement in intrinsic polymyxin and antimicrobial peptide resistance, biofilm formation, and swarming motility of PsrA in Pseudomonas aeruginosa J. Bacteriol. 2008, 190, 5624-5634 10.1128/JB.00594-08
33. Pillai, S. K.; Moellering, R. C.; Eliopoulos, G. M. In Antimicrobial combinations; Antibiotics in Laboratory Medicine Lorian, V., Ed.; Williams and Wilkins: Baltimore, MD, 2005; pp 365-440.
34. Odds, F. C. Synergy, antagonism and what the checkerboard puts between them J. Antimicrob. Chemother. 2003, 52, 1 10.1093/jac/dkg301
35. Ouberai, M.; El Garch, F.; Bussiere, A.; Riou, M.; Alsteens, D.; Lins, L.; Baussanne, I.; Dufrêne, Y. F.; Brasseur, R.; Decout, J. L.; Mingeot-Leclercq, M. P. The Pseudomonas aeruginosa membranes: A target for a new amphiphilic aminoglycoside derivative? Biochim. Biophys. Acta, Biomembr. 2011, 1808, 1716-1727 10.1016/j.bbamem.2011.01.014
36. Paul, K.; Erhardt, M.; Hirano, T.; Blair, D. F.; Hughes, K. T. Energy source of flagellar type III secretion Nature 2008, 451, 489-492 10.1038/nature06497
37. Taber, H. W.; Mueller, J. P.; Miller, P. F.; Arrow, A. S. Bacterial uptake of aminoglycoside antibiotics Microbiol Rev. 1987, 51, 439-457
38. Kumar, A.; Chua, K.-L.; Schweizer, H. P. Method for regulated expression of single-copy efflux pump genes in a surrogate Pseudomonas aeruginosa strain: Identification of the BpeEF-OprC chloramphenicol and trimethoprim efflux pump of Burkholderia pseudomallei 1026b Antimicrob. Agents Chemother. 2006, 50, 3460-3463 10.1128/AAC.00440-06
39. Lomovskaya, O.; Warren, M. S.; Lee, A.; Galazzo, J.; Fronko, R.; Lee, M.; Blais, J.; Cho, D.; Chamberland, S.; Renau, T.; Leger, R.; Hecker, S.; Watkins, W.; Hoshino, K.; Ishida, H.; Lee, V. J. Identification and characterization of inhibitors of multidrug resistance efflux pumps in Pseudomonas aeruginosa: Novel agents for combination therapy Antimicrob. Agents Chemother. 2001, 45, 105-116 10.1128/AAC.45.1.105-116.2001
40. Sträuber, H.; Müller, S. Viability states of bacteria-specific mechanisms of selected probes Cytometry, Part A 2010, 77A, 623-634 10.1002/cyto.a.20920
41. Horobin, R. W.; Stockert, J. C.; Rashid-Doubell, F. Fluorescent cationic probes for nuclei of living cells: why are they selective? A quantitative structure-activity relations analysis Histochem. Cell Biol. 2006, 126, 165-175 10.1007/s00418-006-0156-7
42. Hartmann, M.; Berditsch, M.; Hawecker, J.; Ardakani, M. F.; Gerthsen, D.; Ulrich, A. S. Damage of the bacterial cell envelope by antimicrobial peptides gramicidin S and PGLa as revealed by transmission and scanning electron microscopy Antimicrob. Agents Chemother. 2010, 54, 3132-3142 10.1128/AAC.00124-10
43. Pollard, J. E.; Snarr, J.; Chaudhary, V.; Jennings, J. D.; Shaw, H.; Christiansen, B.; Wright, J.; Jia, W.; Bishop, R. E.; Savage, P. B. In vitro evaluation of the potential for resistance development to ceragenin CSA-13 J. Antimicrob. Chemother. 2012, 67, 2665-2672 10.1093/jac/dks276
44. Tommasi, R.; Brown, D. G.; Walkup, G. K.; Manchester, J. I.; Miller, A. A. Eskaping the labyrinth of antibacterial discovery Nat. Rev. Drug Discovery 2015, 14, 529-542 10.1038/nrd4572
45. Bulitta, J. B.; Ly, N. S.; Landersdorfer, C. B.; Wanigaratne, N. A.; Velkov, T.; Yadav, R.; Oliver, A.; Martin, L.; Shin, B. S.; Forrest, A.; Tsuji, B. T. Two mechanisms of killing Pseudomonas aeruginosa by tobramycin assessed at multiple inocula via mechanism based modeling Antimicrob. Agents Chemother. 2015, 59, 2315-2327 10.1128/AAC.04099-14
46. Hancock, R. E. W.; Sahl, H. G. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies Nat. Biotechnol. 2006, 24, 1551-1557 10.1038/nbt1267
47. Zhanel, G. G.; Ennis, K.; Vercaigne, L.; Walkty, A.; Gin, A. S.; Embil, J.; Smith, H.; Hoban, D. J. A critical review of the fluoroquinoloes: focus on respiratory infections Drugs 2002, 62, 13-59 10.2165/00003495-200262010-00002
48. Farha, M. A.; Verschoor, C. P.; Bowdish, D.; Brown, E. D. Collapsing the proton motive force to identify synergistic combinations against Staphyloccoccus aureus Chem. Biol. 2013, 20, 1168-1178 10.1016/j.chembiol.2013.07.006
49. Feng, X.; Zhu, W.; Schurig-Briccio, L. A.; Lindert, S.; Shoen, C.; Hitchings, R.; Li, J.; Wang, Y.; Baig, N.; Zhou, T.; Kim, B. K.; Crick, D. C.; Cynamon, M.; McCammon, J. A.; Gennis, R. B.; Oldfield, E. Antiinfective targeting enzymes and the proton motive force Proc. Natl. Acad. Sci. U. S. A. 2015, 112, E7073-E7082 10.1073/pnas.1521988112