Drug repurposing as an alternative for the treatment of recalcitrant bacterial infections

Frontiers in Microbiology

Volumn 6, Issue APR, 2015, Pages

  Rangel Vega, Adrián ^a   Bernstein, Lawrence R ^b   Mandujano Tinoco, Edna Ayerim ^c   García Contreras, Silvia Julieta ^d   García Contreras, Rodolfo ^a  

^a UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO   (Mexico)

^b Terrametrix   (United States)

^c INSTITUTO NACIONAL DE MEDICINA GENÓMICA   (Mexico)

^d National Institute of Fisheries and Aquaculture   (Mexico)

Author keywords

5 fluorouracil; Bacterial infections; Ciclopirox; Diflunisal; Drug repurposing; Gallium

Indexed keywords

AZITHROMYCIN; CEFTAZIDIME; CICLOPIROX; CIPROFLOXACIN; DAUNORUBICIN; DIFLUNISAL; DOXORUBICIN; FLUOROURACIL; GALLIUM; METRONIDAZOLE; TINIDAZOLE;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL GROWTH; BACTERIAL INFECTION; BACTERIAL VIRULENCE; BACTERIOPHAGE; CELL COMMUNICATION; CLINICAL TRIAL (TOPIC); CYSTIC FIBROSIS; DNA SYNTHESIS; DRUG REPOSITIONING; GROWTH INHIBITION; HUMAN; MULTIDRUG RESISTANCE; NONHUMAN; PSEUDOMONAS AERUGINOSA; QUORUM SENSING; UPREGULATION;

BACTERIA (MICROORGANISMS);

EID: 84930942830     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2015.00282     Document Type: Article

References (78)

1. Abedon, S. T., Kuhl, S. J., Blasdel, B. G., and Kutter, E. M. (2011). Phage treatment of human infections. Bacteriophage 1, 66-85. doi: 10.4161/bact.1.2.15845.
2. Al-Aoukaty, A., Appanna, V. D., and Falter, H. (1992). Gallium toxicity and adaptation in Pseudomonas fluorescens. FEMS Microbiol. Lett. 71, 265-272. doi: 10.1111/j.1574-6968.1992.tb05272.x.
3. Antunes, L. C., Ferreira, R. B., Buckner, M. M., and Finlay, B. B. (2010). Quorum sensing in bacterial virulence. Microbiology 156, 2271-2282. doi: 10.1099/mic.0.038794-0.
4. Antunes, L. C., Imperi, F., Minandri, F., and Visca, P. (2012). In vitro and in vivo antimicrobial activities of gallium nitrate against multidrug-resistant Acinetobacter baumannii. Antimicrob. Agents Chemother. 56, 5961-5970. doi: 10.1128/AAC.01519-12.
5. Aryee, A., and Price, N. (2014). Antimicrobial stewardship-can we afford to do without it? Br. J. Clin. Pharmacol. 79, 173-178. doi: 10.1111/bcp.12417.
6. Attila, C., Ueda, A., and Wood, T. K. (2009). 5-Fluorouracil reduces biofilm formation in Escherichia coli K-12 through global regulator AriR as an antivirulence compound. Appl. Microbiol. Biotechnol. 82, 525-533. doi: 10.1007/s00253-009-1860-8.
7. Beriault, R., Hamel, R., Chenier, D., Mailloux, R. J., Joly, H., and Appanna, V. D. (2007). The overexpression of NADPH-producing enzymes counters the oxidative stress evoked by gallium, an iron mimetic. Biometals 20, 165-176. doi: 10.1007/s10534-006-9024-0.
8. Bernstein, L. R. (1998). Mechanisms of therapeutic activity for gallium. Pharmacol. Rev. 50, 665-682.
9. Bernstein, L. R., van der Hoeven, J. J., and Boer, R. O. (2011). Hepatocellular carcinoma detection by gallium scan and subsequent treatment by gallium maltolate: rationale and case study. Anticancer Agents Med. Chem. 11, 585-590. doi: 10.2174/187152011796011046.
10. Bernstein, R. L. (2013). "Gallium, therapeutic effects," in Encyclopedia of Metalloproteins, eds R. H. Kretsinger, V. N. Uversky, and E. A. Permyakov (New York, NY: Springer), 823-835. doi: 10.1007/978-1-4614-1533-6_113.
11. Bonchi, C., Imperi, F., Minandri, F., Visca, P., and Frangipani, E. (2014). Repurposing of gallium-based drugs for antibacterial therapy. Biofactors 40, 303-312. doi: 10.1002/biof.1159.
12. Brussow, H. (2012). What is needed for phage therapy to become a reality in Western medicine? Virology 434, 138-142. doi: 10.1016/j.virol.2012.09.015.
13. Carlson-Banning, K. M., Chou, A., Liu, Z., Hamill, R. J., Song, Y., and Zechiedrich, L. (2013). Toward repurposing ciclopirox as an antibiotic against drug-resistant Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae. PLoS ONE 8:e69646. doi: 10.1371/journal.pone.0069646.
14. Chan, B. K., Abedon, S. T., and Loc-Carrillo, C. (2013). Phage cocktails and the future of phage therapy. Future Microbiol. 8, 769-783. doi: 10.2217/fmb.13.47.
15. Chenier, D., Beriault, R., Mailloux, R., Baquie, M., Abramia, G., Lemire, J., et al. (2008). Involvement of fumarase C and NADH oxidase in metabolic adaptation of Pseudomonas fluorescens cells evoked by aluminum and gallium toxicity. Appl. Environ. Microbiol. 74, 3977-3984. doi: 10.1128/AEM.02702-07.
16. Chitambar, C. R. (2010). Medical applications and toxicities of gallium compounds. Int. J. Environ. Res. Public Health 7, 2337-2361. doi: 10.3390/ijerph7052337.
17. Cochis, A., Azzimonti, B., Della Valle, C., Chiesa, R., Arciola, C. R., and Rimondini, L. (2015). Biofilm formation on titanium implants counteracted by grafting gallium and silver ions. J. Biomed. Mater. Res. A 103, 1176-1187. doi: 10.1002/jbm.a.35270.
18. de Leseleuc, L., Harris, G., Kuolee, R., and Chen, W. (2012). In vitro and in vivo biological activities of iron chelators and gallium nitrate against Acinetobacter baumannii. Antimicrob. Agents Chemother. 56, 5397-5400. doi: 10.1128/AAC.00778-12.
19. DeLeon, K., Balldin, F., Watters, C., Hamood, A., Griswold, J., Sreedharan, S., et al. (2009). Gallium maltolate treatment eradicates Pseudomonas aeruginosa infection in thermally injured mice. Antimicrob. Agents Chemother. 53, 1331-1337. doi: 10.1128/AAC.01330-08.
20. Franchini, M., Lusvardi, G., Malavasi, G., and Menabue, L. (2012). Gallium-containing phospho-silicate glasses: synthesis and in vitro bioactivity. Mater. Sci. Eng. C Mater. Biol. Appl. 32, 1401-1406. doi: 10.1016/j.msec.2012.04.016.
21. Frangipani, E., Bonchi, C., Minandri, F., Imperi, F., and Visca, P. (2014). Pyochelin potentiates the inhibitory activity of gallium on Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 58, 5572-5575. doi: 10.1128/AAC.03154-14.
22. García-Contreras, R., Lira-Silva, E., Jasso-Chávez, R., Hernández-González, I., Maeda, T., Hashimoto, T., et al. (2013a). Isolation and characterization of gallium resistant Pseudomonas aeruginosa mutants. Int. J. Med. Microbiol. 303, 574-582. doi: 10.1016/j.ijmm.2013.07.009.
23. García-Contreras, R., Maeda, T., and Wood, T. K. (2013b). Resistance to quorum quenching compounds. Appl. Environ. Microbiol. 79, 6840-6846. doi: 10.1128/AEM.02378-13.
24. García-Contreras, R., Martinez-Vazquez, M., Velazquez Guadarrama, N., Villegas Paneda, A. G., Hashimoto, T., Maeda, T., et al. (2013c). Resistance to the quorum-quenching compounds brominated furanone C-30 and 5-fluorouracil in Pseudomonas aeruginosa clinical isolates. Pathog. Dis. 68, 8-11. doi: 10.1111/2049-632X.12039.
25. García-Contreras, R., Perez-Eretza, B., Lira-Silva, E., Jasso-Chavez, R., Coria-Jimenez, R., Rangel-Vega, A., et al. (2013d). Gallium Induces the production of virulence factors in Pseudomonas aeruginosa. Pathog. Dis. 70, 95-98. doi: 10.1111/2049-632X.12105.
26. Gi, M., Jeong, J., Lee, K., Lee, K. M., Toyofuku, M., Yong, D. E., et al. (2014). A drug-repositioning screening identifies pentetic acid as a potential therapeutic agent for suppressing the elastase-mediated virulence of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 58, 7205-7214. doi: 10.1128/AAC.03063-14.
27. Gieringer, J. H., Wenz, A. F., Just, H. M., and Daschner, F. D. (1986). Effect of 5-fluorouracil, mitoxantrone, methotrexate, and vincristine on the antibacterial activity of ceftriaxone, ceftazidime, cefotiam, piperacillin, and netilmicin. Chemotherapy 32, 418-424. doi: 10.1159/000238445.
28. Hedley, D. W., Tripp, E. H., Slowiaczek, P., and Mann, G. J. (1988). Effect of gallium on DNA synthesis by human T-cell lymphoblasts. Cancer Res. 48, 3014-3018.
29. Heidelberger, C., Chaudhuri, N. K., Danneberg, P., Mooren, D., Griesbach, L., Duschinsky, R., et al. (1957). Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature 179, 663-666. doi: 10.1038/179663a0.
30. Hennessy, E., Mooij, M. J., Legendre, C., Reen, F. J., O'callaghan, J., Adams, C., et al. (2012). Statins inhibit in vitro virulence phenotypes of Pseudomonas aeruginosa. J. Antibiot. (Tokyo) 66, 99-101. doi: 10.1038/ja.2012.95.
31. Hunter, R. C., Asfour, F., Dingemans, J., Osuna, B. L., Samad, T., Malfroot, A., et al. (2013). Ferrous iron is a significant component of bioavailable iron in cystic fibrosis airways. MBio 4, e00557-13. doi: 10.1128/mBio.00557-13.
32. Hussain, M., Collins, C., Hastings, J. G., and White, P. J. (1992). Radiochemical assay to measure the biofilm produced by coagulase-negative staphylococci on solid surfaces and its use to quantitate the effects of various antibacterial compounds on the formation of the biofilm. J. Med. Microbiol. 37, 62-69. doi: 10.1099/00222615-37-1-62.
33. Imperi, F., Leoni, L., and Visca, P. (2014). Antivirulence activity of azithromycin in Pseudomonas aeruginosa. Front. Microbiol. 5:178. doi: 10.3389/fmicb.2014.00178.
34. Imperi, F., Massai, F., Facchini, M., Frangipani, E., Visaggio, D., Leoni, L., et al. (2013a). Repurposing the antimycotic drug flucytosine for suppression of Pseudomonas aeruginosa pathogenicity. Proc. Natl. Acad. Sci. U.S.A. 110, 7458-7463. doi: 10.1073/pnas.1222706110.
35. Imperi, F., Massai, F., Ramachandran Pillai, C., Longo, F., Zennaro, E., Rampioni, G., et al. (2013b). New life for an old drug: the anthelmintic drug niclosamide inhibits Pseudomonas aeruginosa quorum sensing. Antimicrob. Agents Chemother. 57, 996-1005. doi: 10.1128/AAC.01952-12.
36. Kaatz, G. W. (2002). Inhibition of bacterial efflux pumps: a new strategy to combat increasing antimicrobial agent resistance. Expert Opin. Emerg. Drugs 7, 223-233. doi: 10.1517/14728214.7.2.223.
37. Kalia, V. C., Wood, T. K., and Kumar, P. (2014). Evolution of resistance to quorum-sensing inhibitors. Microb. Ecol. 68, 13-23. doi: 10.1007/s00248-013-0316-y.
38. Kaneko, Y., Thoendel, M., Olakanmi, O., Britigan, B. E., and Singh, P. K. (2007). The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity. J. Clin. Invest. 117, 877-888. doi: 10.1172/JCI30783.
39. Kaufmann, G. F., Park, J., and Janda, K. D. (2008). Bacterial quorum sensing: a new target for anti-infective immunotherapy. Expert Opin. Biol. Ther. 8, 719-724. doi: 10.1517/14712598.8.6.719.
40. Khodaverdian, V., Pesho, M., Truitt, B., Bollinger, L., Patel, P., Nithianantham, S., et al. (2013). Discovery of antivirulence agents against methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 57, 3645-3652. doi: 10.1128/AAC.00269-13.
41. Kirkman, H. N., Rolfo, M., Ferraris, A. M., and Gaetani, G. F. (1999). Mechanisms of protection of catalase by NADPH. Kinetics and stoichiometry. J. Biol. Chem. 274, 13908-13914. doi: 10.1074/jbc.274.20.13908.
42. Lee, J., Page, R., Garcia-Contreras, R., Palermino, J. M., Zhang, X. S., Doshi, O., et al. (2007). Structure and function of the Escherichia coli protein YmgB: a protein critical for biofilm formation and acid-resistance. J. Mol. Biol. 373, 11-26. doi: 10.1016/j.jmb.2007.07.037.
43. Levaditi, C., Bardet, J., Tchakirian, A., and Vaisman, A. (1931). Thérapeutique: le gallium, propriétés thérapeutiques dans la syphilis et le trypanosomiases expérimentales. C R Hebd Seances Acad Sci. Ser. D Sci. Nat. 192, 1142-1143.
44. Livermore, D. M. (2009). Has the era of untreatable infections arrived? J. Antimicrob. Chemother. 64(Suppl. 1), i29-i36. doi: 10.1093/jac/dkp255.
45. Lomovskaya, O., and Watkins, W. (2001). Inhibition of efflux pumps as a novel approach to combat drug resistance in bacteria. J. Mol. Microbiol. Biotechnol. 3, 225-236.
46. Lusvardi, G., Malavasi, G., Menabue, L., and Shruti, S. (2013). Gallium-containing phosphosilicate glasses: functionalization and in-vitro bioactivity. Mater. Sci. Eng. C Mater. Biol. Appl. 33, 3190-3196. doi: 10.1016/j.msec.2013.03.046.
47. Maeda, T., García-Contreras, R., Pu, M., Sheng, L., Garcia, L. R., Tomas, M., et al. (2012). Quorum quenching quandary: resistance to antivirulence compounds. ISME J. 6, 493-501. doi: 10.1038/ismej.2011.122.
48. Menon, S., Wagner, H. N. Jr., and Tsan, M. F. (1978). Studies on gallium accumulation in inflammatory lesions: II. Uptake by Staphylococcus aureus: concise communication. J. Nucl. Med. 19, 44-47.
49. Minandri, F., Bonchi, C., Frangipani, E., Imperi, F., and Visca, P. (2014). Promises and failures of gallium as an antibacterial agent. Future Microbiol. 9, 379-397. doi: 10.2217/fmb.14.3.
50. Mullard, A. (2012). Drug repurposing programmes get lift off. Nat. Rev. Drug Discov. 11, 505-506. doi: 10.1038/nrd3776.
51. Niewerth, M., Kunze, D., Seibold, M., Schaller, M., Korting, H. C., and Hube, B. (2003). Ciclopirox olamine treatment affects the expression pattern of Candida albicans genes encoding virulence factors, iron metabolism proteins, and drug resistance factors. Antimicrob. Agents Chemother. 47, 1805-1817. doi: 10.1128/AAC.47.6.1805-1817.2003.
52. Nyhlen, A., Ljungberg, B., Nilsson-Ehle, I., and Odenholt, I. (2002). Bactericidal effect of combinations of antibiotic and antineoplastic agents against Staphylococcus aureus and Escherichia coli. Chemotherapy 48, 71-77. doi: 10.1159/000057665.
53. Olakanmi, O., Britigan, B. E., and Schlesinger, L. S. (2000). Gallium disrupts iron metabolism of mycobacteria residing within human macrophages. Infect. Immun. 68, 5619-5627. doi: 10.1128/IAI.68.10.5619-5627.2000.
54. Olakanmi, O., Gunn, J. S., Su, S., Soni, S., Hassett, D. J., and Britigan, B. E. (2010). Gallium disrupts iron uptake by intracellular and extracellular Francisella strains and exhibits therapeutic efficacy in a murine pulmonary infection model. Antimicrob. Agents Chemother. 54, 244-253. doi: 10.1128/AAC.00655-09.
55. Perlmutter, J. I., Forbes, L. T., Krysan, D. J., Ebsworth-Mojica, K., Colquhoun, J. M., Wang, J. L., et al. (2014). Repurposing the antihistamine terfenadine for antimicrobial activity against Staphylococcus aureus. J. Med. Chem. 57, 8540-8562. doi: 10.1021/jm5010682.
56. Perry, A. C., Ni Bhriain, N., Brown, N. L., and Rouch, D. A. (1991). Molecular characterization of the gor gene encoding glutathione reductase from Pseudomonas aeruginosa: determinants of substrate specificity among pyridine nucleotide-disulphide oxidoreductases. Mol. Microbiol. 5, 163-171. doi: 10.1111/j.1365-2958.1991.tb01837.x.
57. Pinault, L., Han, J. S., Kang, C. M., Franco, J., and Ronning, D. R. (2013). Zafirlukast inhibits complexation of Lsr2 with DNA and growth of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 57, 2134-2140. doi: 10.1128/AAC.02407-12.
58. Poole, K. (2011). Pseudomonas aeruginosa: resistance to the max. Front. Microbiol. 2:65. doi: 10.3389/fmicb.2011.00065.
59. Rasko, D. A., and Sperandio, V. (2010). Anti-virulence strategies to combat bacteria-mediated disease. Nat. Rev. Drug Discov. 9, 117-128. doi: 10.1038/nrd3013.
60. Rosch, J. W., Boyd, A. R., Hinojosa, E., Pestina, T., Hu, Y., Persons, D. A., et al. (2010). Statins protect against fulminant pneumococcal infection and cytolysin toxicity in a mouse model of sickle cell disease. J. Clin. Invest. 120, 627-635. doi: 10.1172/JCI39843.
61. Ross-Gillespie, A., Weigert, M., Brown, S. P., and Kummerli, R. (2014). Gallium-mediated siderophore quenching as an evolutionarily robust antibacterial treatment. Evol. Med. Public Health 2014, 18-29. doi: 10.1093/emph/eou003.
62. Rzhepishevska, O., Ekstrand-Hammarstrom, B., Popp, M., Bjorn, E., Bucht, A., Sjostedt, A., et al. (2011). The antibacterial activity of Ga3+ is influenced by ligand complexation as well as the bacterial carbon source. Antimicrob. Agents Chemother. 55, 5568-5580. doi: 10.1128/AAC.00386-11.
63. Seo, M. D., Won, H. S., Kim, J. H., Mishig-Ochir, T., and Lee, B. J. (2012). Antimicrobial peptides for therapeutic applications: a review. Molecules 17, 12276-12286. doi: 10.3390/molecules171012276.
64. Shruti, S., Salinas, A. J., Lusvardi, G., Malavasi, G., Menabue, L., and Vallet-Regi, M. (2013). Mesoporous bioactive scaffolds prepared with cerium-, gallium-and zinc-containing glasses. Acta Biomater 9, 4836-4844. doi: 10.1016/j.actbio.2012.09.024.
65. Sigle, H. C., Thewes, S., Niewerth, M., Korting, H. C., Schafer-Korting, M., and Hube, B. (2005). Oxygen accessibility and iron levels are critical factors for the antifungal action of ciclopirox against Candida albicans. J. Antimicrob. Chemother. 55, 663-673. doi: 10.1093/jac/dki089.
66. Skindersoe, M. E., Alhede, M., Phipps, R., Yang, L., Jensen, P. O., Rasmussen, T. B., et al. (2008). Effects of antibiotics on quorum sensing in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 52, 3648-3663. doi: 10.1128/AAC.01230-07.
67. Srivastava, T. N., Bajpai, K. K., and Singh, K. (1973). Anti-microbial activities of diaryl gallium, indium and thallium compounds. Indian J. Agric. Sci. 43, 89-93.
68. Struss, A. K., Pasini, P., Flomenhoft, D., Shashidhar, H., and Daunert, S. (2012). Investigating the effect of antibiotics on quorum sensing with whole-cell biosensing systems. Anal. Bioanal. Chem. 402, 3227-3236. doi: 10.1007/s00216-012-5710-7.
69. Subissi, A., Monti, D., Togni, G., and Mailland, F. (2010). Ciclopirox: recent nonclinical and clinical data relevant to its use as a topical antimycotic agent. Drugs 70, 2133-2152. doi: 10.2165/11538110-000000000-00000.
70. Ueda, A., Attila, C., Whiteley, M., and Wood, T. K. (2009). Uracil influences quorum sensing and biofilm formation in Pseudomonas aeruginosa and fluorouracil is an antagonist. Microb. Biotechnol. 2, 62-74. doi: 10.1111/j.1751-7915.2008.00060.x.
71. Valappil, S. P., Ready, D., Abou Neel, E. A., Pickup, D. M., O'dell, L. A., Chrzanowski, W., et al. (2009). Controlled delivery of antimicrobial gallium ions from phosphate-based glasses. Acta Biomater 5, 1198-1210. doi: 10.1016/j.actbio.2008.09.019.
72. Valappil, S. P., Yiu, H. H., Bouffier, L., Hope, C. K., Evans, G., Claridge, J. B., et al. (2013). Effect of novel antibacterial gallium-carboxymethyl cellulose on Pseudomonas aeruginosa. Dalton Trans. 42, 1778-1786. doi: 10.1039/C2DT32235H.
73. Vermes, A., Guchelaar, H. J., and Dankert, J. (2000). Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions. J. Antimicrob. Chemother. 46, 171-179. doi: 10.1093/jac/46.2.171.
74. Waldorf, A. R., and Polak, A. (1983). Mechanisms of action of 5-fluorocytosine. Antimicrob. Agents Chemother. 23, 79-85. doi: 10.1128/AAC.23.1.79.
75. Walsh, C. T., and Wencewicz, T. A. (2014). Prospects for new antibiotics: a molecule-centered perspective. J. Antibiot. (Tokyo) 67, 7-22. doi: 10.1038/ja.2013.49.
76. Walz, J. M., Avelar, R. L., Longtine, K. J., Carter, K. L., Mermel, L. A., and Heard, S. O. (2010). Anti-infective external coating of central venous catheters: a randomized, noninferiority trial comparing 5-fluorouracil with chlorhexidine/silver sulfadiazine in preventing catheter colonization. Crit. Care Med. 38, 2095-2102. doi: 10.1097/CCM.0b013e3181f265ba.
77. Weiss, R. B. (1992). The anthracyclines: will we ever find a better doxorubicin? Semin. Oncol. 19, 670-686.
78. West, T. P., and Chu, C. P. (1986). Utilization of pyrimidines and pyrimidine analogues by fluorescent pseudomonads. Microbios 47, 149-157.