Progress against Escherichia coli with the oxazolidinone class of antibacterials: Test case for a general approach to improving whole-cell gram-negative activity

ACS Infectious Diseases

Volumn 2, Issue 6, 2016, Pages 405-426

  Takrouri, Khuloud ^a   Cooper, Harold D ^a,d   Spaulding, Andrew ^b   Zucchi, Paola ^b   Koleva, Bilyana ^b   Cleary, Dillon C ^a,e   Tear, Westley ^b   Beuning, Penny J ^b   Hirsch, Elizabeth B ^b   Aggen, James B ^c  

^a Northeastern University ^*  (United States)

^b NORTHEASTERN UNIVERSITY   (United States)

^c Revolution Medicines Inc   (United States)

^d Rexahn Pharmaceuticals Inc   (United States)

^e Spring Bank Pharmaceuticals Inc S 7   (United States)

Author keywords

efflux pump; Gram negative; outer membrane permeability; oxazolidinones; porins

Indexed keywords

2' FLUORO 3 HYDROXY 4' [5 (HYDROXYMETHYL) 2 OXOOXAZOLIDIN 3 YL] (1,1' BIPHENYL) 4 CARBALDEHYDE; 2' FLUORO 3 HYDROXY 4' [5 (HYDROXYMETHYL) 2 OXOOXAZOLIDIN 3 YL] (1,1' BIPHENYL) 4 CARBONITRILE; 2' FLUORO 4 HYDROXY 4' [5 (HYDROXYMETHYL) 2 OXOOXAZOLIDIN 3 YL] (1,1' BIPHENYL) 3 CARBONITRILE; 2' FLUORO 5 HYDROXY 4' [5 (HYDROXYMETHYL) 2 OXOOXAZOLIDIN 3 YL] (1,1' BIPHENYL) 2 CARBONITRILE; 2' FLUORO 5 HYDROXY 4' [5 (HYDROXYMETHYL) 2 OXOOXAZOLIDIN 3 YL] (1,1' BIPHENYL) 3 CARBONITRILE; 3 [2 FLUORO 2' HYDROXY (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [2 FLUORO 3' HYDROXY (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [2 FLUORO 3' HYDROXY 4' NITRO (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [2 FLUORO 4' HYDROXY (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [2 FLUORO 4' HYDROXY 3' (TRIFLUOROMETHOXY) (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [2 FLUORO 4' HYDROXY 3' (TRIFLUOROMETHYL) (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [2 FLURO (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [2' (AMINOMETHYL) 2 FLUORO (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [2,2' DIFLUORO 3' HYDROXY (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [2,2' DIFLUORO 5' HYDROXY (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [2,3' DIFLUORO 4' HYDROXY (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [2,4' DIFLUORO 3' HYDROXY (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [3' (AMINOMETHYL) 2 FLUORO (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [3' AMINO 2 FLUORO 4' HYDROXY (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [4' (AMINOMETHYL) 2 FLUORO (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [4' AMINO 2 FLUORO 3' HYDROXY (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; 3 [4' [(DIMETHYLAMINO)METHYL] 2 FLUORO (1,1' BIPHENYL) 4 YL] 5 (HYDROXYMETHYL)OXAZOLIDIN 2 ONE; AMPHOLYTE; ANTIBIOTIC AGENT; LINEZOLID; N [2',4 DIFLUORO 4' [5 (HYDROXYMETHYL) 2 OXOOXAZOLIDIN 3 YL] (1,1' BIPHENYL) 3 YL]METHANESULFONAMIDE; N [2',4 DIFLUORO 4' [5 (HYDROXYMETHYL) 2 OXOOXAZOLIDIN 3 YL] (1,1' BIPHENYL) 3 YL]MORPHOLINE 4 SULFONAMIDE; OXAZOLIDINONE DERIVATIVE; TEDIZOLID; UNCLASSIFIED DRUG; UNINDEXED DRUG; ANTIINFECTIVE AGENT;

ACIDITY; ARTICLE; BACTERIAL OUTER MEMBRANE; CONTROLLED STUDY; CRYSTAL STRUCTURE; ESCHERICHIA COLI; HYDROPHOBICITY; MEMBRANE PERMEABILITY; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; PERIPLASM; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; RNA TRANSLATION; STAPHYLOCOCCUS AUREUS; STRUCTURE ACTIVITY RELATION; SUZUKI REACTION; WHOLE CELL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; ESCHERICHIA COLI INFECTION; GRAM NEGATIVE BACTERIUM; GRAM NEGATIVE INFECTION; HUMAN; MICROBIAL SENSITIVITY TEST; MICROBIOLOGY; PHYSIOLOGY; SYNTHESIS;

ANTI-BACTERIAL AGENTS; ESCHERICHIA COLI; ESCHERICHIA COLI INFECTIONS; GRAM-NEGATIVE BACTERIA; GRAM-NEGATIVE BACTERIAL INFECTIONS; HUMANS; MICROBIAL SENSITIVITY TESTS; MOLECULAR STRUCTURE; OXAZOLIDINONES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 85006186498     PISSN: None     EISSN: 23738227     Source Type: Journal    
DOI: 10.1021/acsinfecdis.6b00003     Document Type: Article

References (39)

1. Peleg, A. Y. and Hooper, D. C. (2010) Hospital-acquired infections due to Gram-negative bacteria N. Engl. J. Med. 362, 1804-1813 10.1056/NEJMra0904124
2. Spellberg, B., Guidos, R., Gilbert, D., Bradley, J., Boucher, H. W., and Scheld, W. M. et al. 2008, The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America Clin. Infect. Dis. 46, 155-164 10.1086/524891
3. Hampton, T. (2013) Report reveals scope of US antibiotic resistance threat JAMA 310, 1661-1663 10.1001/jama.2013.280695
4. Boucher, H. W., Talbot, G. H., Benjamin, D. K., Jr., Bradley, J., Guidos, R. J., and Jones, R. N. et al. 2013, 10 × '20 Progress-development of new drugs active against Gram-negative bacilli: an update from the Infectious Diseases Society of America Clin. Infect. Dis. 56, 1685-1694 10.1093/cid/cit152
5. Spellberg, B. and Shlaes, D. (2014) Prioritized current unmet needs for antibacterial therapies Clin. Pharmacol. Ther. 96, 151-153 10.1038/clpt.2014.106
6. Silver, L. L. (2011) Challenges of antibacterial discovery Clin. Microbiol. Rev. 24 (1) 71-109 10.1128/CMR.00030-10
7. Nikaido, H. (2003) Molecular basis of bacterial outer membrane permeability revisited Microbiol. Mol. Biol. Rev. 67 (4) 593-656 10.1128/MMBR.67.4.593-656.2003
8. Nakae, T., Ishii, J. N., Tokunaga, H., Kobayashi, Y., and Nakae, R. (1982) The solute selectivity of porin pores of Escherichia coli and Salmonella typhimurium Tokai J. Exp. Clin. Med. 7 (Suppl.) 141-148
9. Nikaido, H. and Thanassi, D. G. (1993) Penetration of lipophilic agents with multiple protonation sites into bacterial cells: tetracyclines and fluoroquinolones as examples Antimicrob. Agents Chemother. 37, 1393-1399 10.1128/AAC.37.7.1393
10. Manchester, J. I., Buurman, E. T., Bisacchi, G. S., and McLaughlin, R. E. (2012) Molecular determinants of AcrB-mediated bacterial efflux implications for drug discovery J. Med. Chem. 55, 2532-2537 10.1021/jm201275d
11. O'Shea, R. and Moser, H. E. (2008) Physicochemical properties of antibacterial compounds: implications for drug discovery J. Med. Chem. 51 (10) 2871-2878 10.1021/jm700967e
12. Domagala, J. M., Hanna, L. D., Heifetz, C. L., Hutt, M. P., Mich, T. F., and Sanchez, J. P. et al. 1986, New structure-activity relationships of the quinolone antibacterials using the target enzyme. The development and application of a DNA gyrase assay J. Med. Chem. 29, 394-404 10.1021/jm00153a015
13. Brown, D. G., May-Dracka, T. L., Gagnon, M. M., and Tommasi, R. (2014) Trends and exceptions of physical properties on antibacterial activity for Gram-positive and Gram-negative pathogens J. Med. Chem. 57, 10144-10161 10.1021/jm501552x
14. Tommasi, R., Brown, D. G., Walkup, G. K., Manchester, J. I., and Miller, A. A. (2015) ESKAPEing the labyrinth of antibacterial discovery Nat. Rev. Drug Discovery 14, 529 10.1038/nrd4572
15. Michalska, K., Karpiuk, I., Krol, M., and Tyski, S. (2013) Recent development of potent analogues of oxazolidinone antibacterial agents Bioorg. Med. Chem. 21, 577-591 10.1016/j.bmc.2012.11.036
16. Guo, B., Fan, H., Xin, Q., Chu, W., Wang, H., Huang, Y., Chen, X., and Yang, Y. (2013) Solubility-Driven Optimization of (Pyridin-3-yl) Benzoxazinyloxazolidinones Leading to a Promising Antibacterial Agent J. Med. Chem. 56, 2642-2650 10.1021/jm4000598
17. Srivastava, B. K., Soni, R., Patel, J. Z., Jain, M. R., and Patel, P. R. (2008) Oxazolidinone Antibacterials and Our Experience Anti-Infect. Agents Med. Chem. 7, 258-280 10.2174/187152108785908820
18. Genin, M. J., Allwine, D. A., and Anderson, D. J. et al. 2000, Substituent Effects on the Antibacterial Activity of Nitrogen-Carbon-Linked (Azolylphenyl)oxazolidinones with Expanded Activity Against the Fastidious Gram-Negative Organisms Haemophilus influenzae and Moraxella catarrhalis J. Med. Chem. 43, 953-970 10.1021/jm990373e
19. Louie, A., Liu, W., Kulawy, R., and Drusano, G. L. (2011) In vivo pharmacodynamics of torezolid phosphate (TR-701), a new oxazolidinone antibiotic, against methicillin-susceptible and methicillin-resistant Staphyloccocus aureus strains in a mouse thigh infection model Antimicrob. Agents Chemother. 55 (7) 3453-3460 10.1128/AAC.01565-10
20. Lepak, A. J., Marchillo, K., Pichereau, S., Craig, W. A., and Andes, D. R. (2012) Comparative pharmacodynamics of the new oxazolidinone tedizolid phosphate in a neutropenic murine Staphyloccocus aureus pneumonia model Antimicrob. Agents Chemother. 56 (11) 5916-5922 10.1128/AAC.01303-12
21. Renslo, A. R. (2010) Antibacterial oxazolidinones: emerging structure-toxicity relationships Expert Rev. Anti-Infect. Ther. 8 (5) 565-574 10.1586/eri.10.26
22. Reck, F., Zhou, F., and Eyermann, C. J. et al. 2007, Novel substituted (pyridine-3-yl)phenyloxazolidinones: antibacterial agents with reduced activity against monoamine oxidase A and increased solubility J. Med. Chem. 50, 4868-4881 10.1021/jm070428+
23. Gerson, S. L., Kaplan, S. L., and Bruss, J. B. et al. 2002, Hematologic effects of linezolid: summary of clinical experience Antimicrob. Agents Chemother. 46 (8) 2723-2726 10.1128/AAC.46.8.2723-2726.2002
24. Shaw, K. J. and Barbachyn, M. R. (2011) The oxazolidinones: past, present, and future Ann. N.Y. Acad. Sci. 1241, 48-70 10.1111/j.1749-6632.2011.06330.x
25. Woo, J. Y., Bin Im, W., Kaol Rhee, J., Ja Shim, M., Bae Kim, W., and Chil Choi, E. (2004) Synthesis and antibacterial activity of oxazolidinones containing pyridine substituted with heteroaromatic ring Bioorg. Med. Chem. 12, 5909-5915 10.1016/j.bmc.2004.08.025
26. Wilson, D. N., Schluenzen, F., Harms, J. M., Starosta, A. L., Connell, S. R., and Fucini, P. (2008) The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning Proc. Natl. Acad. Sci. U.S.A. 105 (36) 13339-13344 10.1073/pnas.0804276105
27. Gu, B., Kelesidis, T., and Tsiaodras, S. et al. 2013, The emerging problem of linezolid-resistant Staphylococcus J. Antimicrob. Chemother. 68 (1) 4-11 10.1093/jac/dks354
28. Diaz, L., Kiratisin, P., and Mendes, R. E. et al. 2012, Transferable plasmid-mediated resistance to linezolid due to cfr in a human clinical isolate of Enterococcus faecalis Antimicrob. Agents Chemother. 56 (7) 3917-3922 10.1128/AAC.00419-12
29. Mendes, R. E., Hogan, P. A., Streit, J. M., Jones, R. N., and Flamm, R. K. (2014) Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) Program: report of linezolid activity over 9 years (2004-12) J. Antimicrob. Chemother. 69, 1582-1588 10.1093/jac/dkt54
30. Locke, J. B., Finn, J., and Hilgers, M. et al. 2010, Structure-activity relationships of diverse oxazolidinones for linezolid-resistant Staphyloccocus aureus strains possessing the cfr-methyltransferase gene or ribosomal mutations Antimicrob. Agents Chemother. 54 (12) 5337-5343 10.1128/AAC.00663-10
31. Lawrence, L., Danese, P., and DeVito, J. et al. 2008, In vitro activity of Rx-01 oxazolidinones against hospital and community pathogens Antimicrob. Agents Chemother. 52 (5) 1653-1662 10.1128/AAC.01383-07
32. Schumacher, A., Trittler, R., and Bohnert, J. A. et al. 2007, Intracellular accumulation of linezolid in Escherichia coli, Citrobacter freundii, and Enterbacter aerogenes: role of enhanced efflux pump activity and inactivation J. Antimicrob. Chemother. 59, 1261-1264 10.1093/jac/dkl380
33. Schaadt, R., Sweeney, D., Shinabarger, D., and Zurenko, D. (2009) In Vitro Activity of TR-700, the Active Ingredient of the Antibacterial Prodrug TR-701, a Novel Oxazolidinone Antibacterial Agent Antimicrob. Agents Chemother. 53, 3236-3239 10.1128/AAC.00228-09
34. Ippolito, J. A., Kanyo, Z. F., Wang, D., Franceschi, F. J., Steitz, T. A., and Duffy, E. M. (2008) Crystal Structure of the Oxazolidinone Antibiotic Linezolid Bound to the 50S Ribosomal Subunit J. Med. Chem. 51, 3353-3356 10.1021/jm800379d
35. Zgurskaya, H. I., Krishnamoorthy, G., Ntreh, A., and Lu, S. (2011) Mechanism and Function of the Outer Membrane Channel TolC in Multidrug Resistance and Physiology of Enterobacteria Front. Microbiol. 2, 00189 10.3389/fmicb.2011.00189
36. Clinical and Laboratory Standards Institute. (2014) Performance Standards for Antimicrobial Susceptibility Testing, Twentieth Informational Supplement, M100-S24, Clinical and Laboratory Standards Institute, Wayne, PA, USA.
37. Sahalan, A. Z. and Dixon, R. A. (2008) Role of the cell envelope in the antibacterial activities of polymyxin B and polymyxin B nonapeptide against Escherichia coli Int. J. Antimicrob. Agents 31 (3) 224-227 10.1016/j.ijantimicag.2007.10.005
38. Poole, K. (2000) Efflux-mediated resistance to fluoroquinolones in Gram-negative bacteria Antimicrob. Agents Chemother. 44 (9) 2233-2341 10.1128/AAC.44.9.2233-2241.2000
39. Singh, R. et al. 2012, Temporal interplay between efflux pumps and target mutations in development of antibiotic resistance in Escherichia coli Antimicrob. Agents Chemother. 56 (4) 1680-1685 10.1128/AAC.05693-11