The antibiotic resistome: Challenge and opportunity for therapeutic intervention

Future Medicinal Chemistry

Volumn 4, Issue 3, 2012, Pages 347-359

  Martínez, José L ^a  

^a CENTRO NACIONAL DE BIOTECNOLOGÍA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; BACTERIAL PROTEIN; BETA LACTAMASE; BETA LACTAMASE INHIBITOR; CLAVULANIC ACID; RESISTOME; SULBACTAM; TAZOBACTAM; UNCLASSIFIED DRUG;

ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; ARTICLE; DRUG TARGETING; MULTIDRUG RESISTANCE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL;

ANIMALS; ANTI-BACTERIAL AGENTS; BACTERIA; BACTERIAL INFECTIONS; DRUG DISCOVERY; DRUG RESISTANCE, BACTERIAL; HUMANS;

EID: 84858035236     PISSN: 17568919     EISSN: 17568927     Source Type: Journal    
DOI: 10.4155/fmc.12.2     Document Type: Article

References (105)

1. WHO. Overcoming Antibiotics Resistance. World Health Organization Report in Infectious Disease (2000).
2. Martinez JL, Fajardo A, Garmendia L et al. A global view of antibiotic resistance. FEMS Microbiol. Rev. 33(1), 44-65 (2009). Presents an ecological point of view on the origin and evolution of antibiotic resistance.
3. Benton MJ. Evolutionary biology: new take on the Red Queen. Nature 463(7279), 306-307 (2010).
4. Jabes D. The antibiotic R&D pipeline: an update. Curr. Opin. Microbiol. (14)5, 564-569 (2011).
5. Martinez JL, Baquero F, Andersson DI. Beyond serial passages: new methods for predicting the emergence of resistance to novel antibiotics. Curr. Opin. Pharmacol. (2011).
6. Martinez JL, Rojo F, Vila J. Are nonlethal targets useful for developing novel antimicrobials? Future Microbiol. 6, 605-607 (2011).
7. Rasko DA, Sperandio V. Anti-virulence strategies to combat bacteria-mediated disease. Nature Rev. 9(2), 117-128 (2010).
8. Bush K. Beta-lactamase inhibitors from laboratory to clinic. Clin. Microbiol. Rev. 1(1), 109-123 (1988).
9. Reading C, Cole M. Clavulanic acid: a beta-lactamase-inhibiting beta-lactam from Streptomyces clavuligerus. Antimicrob. Agents Chemother. 11(5), 852-857 (1977).
10. Martinez JL, Vicente MF, Delgado-Iribarren A, Perez-Diaz JC, Baquero F. Small plasmids are involved in amoxicillin-clavulanate resistance in Escherichia coli. Antimicrob. Agents Chemother. 33(4), 595 (1989).
11. Martinez JL, Cercenado E, Rodriguez-Creixems M, Vincente-Perez MF, Delgado-Iribarren A, Baquero F. Resistance to beta-lactam/clavulanate. Lancet 2(8573), 1473 (1987).
12. Salverda ML, De Visser JA, Barlow M. Natural evolution of TEM-1 beta-lactamase: experimental reconstruction and clinical relevance. FEMS Microbiol. Rev. 34(6), 1015-1036 (2010).
13. Hancock RE. Resistance mechanisms in Pseudomonas aeruginosa and other nonfermentative gram-negative bacteria. Clin. Infect. Dis. 27 S93-S99 (1998).
14. Zhang Y, Heym B, Allen B, Young D, Cole S. The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature 358(6387), 591-593 (1992).
15. Li XZ, Nikaido H. Efflux-mediated drug resistance in bacteria. Drugs 64(2), 159-204 (2004).
16. Poole K. Efflux-mediated antimicrobial resistance. J. Antimicrob. Chemother. 56(1), 20-51 (2005).
17. Alekshun MN, Levy SB. Molecular mechanisms of antibacterial multidrug resistance. Cell 128(6), 1037-1050 (2007). Updated review on the mechanims of antibiotic resistance.
18. Piddock LJ. Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin. Microbiol. Rev. 19(2), 382-402 (2006).
19. Webber MA, Piddock LJ. The importance of efflux pumps in bacterial antibiotic resistance. J. Antimicrob. Chemother. 51(1), 9-11 (2003).
20. Alvarez-Ortega C, Weigand I, Olivares J, Hancock RE, Martinez JL. The intrinsic resistome of Pseudomonas aeruginosa to beta-lactams. Virulence 2, 144-146 (2011).
21. Alvarez-Ortega C, Wiegand I, Olivares J, Hancock RE, Martinez JL. Genetic determinants involved in the susceptibility of Pseudomonas aeruginosa to beta-lactam antibiotics. Antimicrob. Agents Chemother. 54(10), 4159-4167 (2010).
22. Fajardo A, Martinez-Martin N, Mercadillo M et al. The neglected intrinsic resistome of bacterial pathogens. PLoS ONE 3(2), e1619 (2008). Introduces the concept of 'intrinsic resistome' and highlights that the phenotype of intrinsic resistance is the consequence of the activity of several elements, including those forming part of the basic microbial physiology.
23. Girgis HS, Hottes AK, Tavazoie S. Genetic architecture of intrinsic antibiotic susceptibility. PLoS ONE 4(5), e5629 (2009).
24. Tamae C, Liu A, Kim K et al. Determination of antibiotic hypersensitivity among 4,000 single-gene-knockout mutants of Escherichia coli. J. Bacteriol. 190(17), 5981-5988 (2008).
25. Liu A, Tran L, Becket E et al. Antibiotic sensitivity profiles determined with an Escherichia coli gene knockout collection: generating an antibiotic bar code. Antimicrob. Agents Chemother. 54(4), 1393-1403 (2010). Comprehensive analysis of the intrinsic resistome of Escherichia coli.
26. Kronvall G. Normalized resistance interpretation as a tool for establishing epidemiological MIC susceptibility breakpoints. J. Clin. Microbiol. 48(12), 4445-4452 (2010).
27. Fajardo A, Linares JF, Martinez JL. Towards an ecological approach to antibiotics and antibiotic resistance genes. Clin. Microbiol. Infect. 15(Suppl. 1), 14-16 (2009).
28. Martinez JL, Baquero F, Andersson DI. Predicting antibiotic resistance. Nature Rev. Microbiol. 5(12), 958-965 (2007).
29. Reguera JA, Baquero F, Perez-Diaz JC, Martinez JL. Factors determining resistance to beta-lactam combined with beta-lactamase inhibitors in Escherichia coli. J. Antimicrob. Chemother. 27(5), 569-575 (1991).
30. Chollet R, Chevalier J, Bryskier A, Pages JM. The AcrAB-TolC pump is involved in macrolide resistance but not in telithromycin efflux in Enterobacter aerogenes and Escherichia coli. Antimicrob. Agents Chemother. 48(9), 3621-3624 (2004).
31. Baucheron S, Imberechts H, Chaslus-Dancla E, Cloeckaert A. The AcrB multidrug transporter plays a major role in high-level fluoroquinolone resistance in Salmonella enterica serovar typhimurium phage type DT204. Microb. Drug Resist. 8(4), 281-289 (2002).
32. Jalal S, Wretlind B. Mechanisms of quinolone resistance in clinical strains of Pseudomonas aeruginosa. Microb. Drug Resist. 4(4), 257-261 (1998).
33. Lunn AD, Fabrega A, Sanchez-Cespedes J, Vila J. Prevalence of mechanisms decreasing quinolone-susceptibility among Salmonella spp. clinical isolates. Int. Microbiol. 13(1), 15-20 (2010).
34. Olliver A, Valle M, Chaslus-Dancla E, Cloeckaert A. Role of an acrR mutation in multidrug resistance of in vitro-selected fluoroquinolone-resistant mutants of Salmonella enterica serovar Typhimurium. FEMS Microbiol. Lett. 238(1), 267-272 (2004).
35. Singh M, Jadaun GP, Ramdas et al. Effect of efflux pump inhibitors on drug susceptibility of ofloxacin resistant Mycobacterium tuberculosis isolates. Indian J. Med. Res. 133(5), 535-540 (2011).
36. Vila J, Martinez JL. Clinical impact of the over-expression of efflux pump in nonfermentative Gram-negative bacilli, development of efflux pump inhibitors. Curr. Drug Targets 9(9), 797-807 (2008).
37. Drawz SM, Bonomo RA. Three decades of beta-lactamase inhibitors. Clin. Microbiol. Rev. 23(1), 160-201 (2010). Authoritative and comprehensive review on β-lactamase inhibitors.
38. Budzikiewicz H. Siderophore-antibiotic conjugates used as trojan horses against Pseudomonas aeruginosa. Curr. Top. Med. Chem. 1(1), 73-82 (2001).
39. Page MG, Dantier C, Desarbre E, Gaucher B, Gebhardt K, Schmitt-Hoffmann A. In vitro and in vivo properties of BAL30376, a beta-lactam and dual beta-lactamase inhibitor combination with enhanced activity against Gram-negative bacilli that express multiple beta-lactamases. Antimicrob. Agents Chemother. 55(4), 1510-1519 (2011).
40. Livermore DM, Mushtaq S, Warner M. Activity of BAL30376 (monobactam BAL19764 + BAL29880 + clavulanate) versus Gram-negative bacteria with characterized resistance mechanisms. J. Antimicrob. Chemother. 65(11), 2382-2395 (2010).
41. Kiener PA, Waley SG. Reversible inhibitors of penicillinases. Biochem. J. 169(1), 197-204 (1978).
42. Tan Q, Ogawa AM, Painter RE, Park YW, Young K, DiNinno FP. 4,7-Dichloro benzothien-2-yl sulfonylaminomethyl boronic acid: first boronic acid-derived beta-lactamase inhibitor with class A, C, and D activity. Bioorg. Med. Chem. Lett. 20(8), 2622-2624 (2010).
43. Morrison MJ, Li N, Pratt RF. Inverse acyl phosph(on)ates: substrates or inhibitors of beta-lactam-recognizing enzymes? Bioorg. Chem. 29(5), 271-281 (2001).
44. Pratt RF. Inhibition of a class C beta-lactamase by a specific phosphonate monoester. Science 246(4932), 917-919 (1989).
45. Ganta SR, Perumal S, Pagadala SR et al. Approaches to the simultaneous inactivation of metallo- and serine-beta-lactamases. Bioorg. Med. Chem. Lett. 19(6), 1618-1622 (2009).
46. Pelto RB, Pratt RF. Kinetics and mechanism of inhibition of a serine beta-lactamase by O-aryloxycarbonyl hydroxamates. Biochemistry 47(46), 12037-12046 (2008).
47. Mezes PS, Clarke AJ, Dmitrienko GI, Viswanatha T. 6-beta- (Trifluoromethane sulfonyl)-amido-penicillanic acid sulfone: a potent inhibitor for beta-lactamases. FEBS Lett. 143(2), 265-267 (1982).
48. Page MI, Hinchliffe PS, Wood JM, Harding LP, Laws AP. Novel mechanism of inhibiting beta-lactamases by sulfonylation using beta-sultams. Bioorg. Med. Chem. Lett. 13(24), 4489-4492 (2003).
49. Saier MH, Jr., Paulsen IT, Sliwinski MK, Pao SS, Skurray RA, Nikaido H. Evolutionary origins of multidrug and drug-specific efflux pumps in bacteria. Faseb J. 12(3), 265-274 (1998).
50. Nikaido H, Takatsuka Y. Mechanisms of RND multidrug efflux pumps. Biochim. Biophys. Acta 1794(5), 769-781 (2009).
51. Paulsen IT, Chen J, Nelson KE, Saier MH Jr. Comparative genomics of microbial drug efflux systems. J. Mol. Microbiol. Biotechnol. 3(2), 145-150 (2001).
52. Saier MH Jr, Paulsen IT. Phylogeny of multidrug transporters. Semin. Cell Dev. Biol. 12(3), 205-213 (2001).
53. Paulsen IT. Multidrug efflux pumps and resistance: regulation and evolution. Curr. Opin. Microbiol. 6(5), 446-451 (2003).
54. Lomovskaya O, Watkins W. Inhibition of efflux pumps as a novel approach to combat drug resistance in bacteria. J. Mol. Microbiol. Biotechnol. 3(2), 225-236 (2001).
55. Blair JM, Piddock LJ. Structure, function and inhibition of RND efflux pumps in Gram-negative bacteria: an update. Curr. Opin. Microbiol. 12(5), 512-519 (2009).
56. Stavri M, Piddock LJ, Gibbons S. Bacterial efflux pump inhibitors from natural sources. J. Antimicrob. Chemother. 59(6), 1247-1260 (2007).
57. Lomovskaya O, Warren MS, Lee A et al. Identification and characterization of inhibitors of multidrug resistance efflux pumps in Pseudomonas aeruginosa: novel agents for combination therapy. Antimicrob. Agents Chemother. 45(1), 105-116 (2001). Description of inhibitors of multidrug efflux pumps that reduce bacterial susceptibility to several antibiotics.
58. Lomovskaya O, Bostian KA. Practical applications and feasibility of efflux pump inhibitors in the clinic - a vision for applied use. Biochemical. Pharmacol. 71(7), 910-918 (2006).
59. Mahamoud A, Chevalier J, Davin-Regli A, Barbe J, Pages JM. Quinoline derivatives as promising inhibitors of antibiotic efflux pump in multidrug resistant Enterobacter aerogenes isolates. Curr. Drug Targets 7(7), 843-847 (2006).
60. Yoshida K, Nakayama K, Ohtsuka M et al. MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 7: highly soluble and in vivo active quaternary ammonium analogue D13-9001, a potential preclinical candidate. Bioorg. Med. Chem. 15(22), 7087-7097 (2007).
61. Piddock LJ. Multidrug-resistance efflux pumps - not just for resistance. Nat. Rev. Microbiol. 4(8), 629-636 (2006).
62. Martinez JL, Sanchez MB, Martinez-Solano L et al. Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems. FEMS Microbiol. Rev. 33(2), 430-449 (2009).
63. Hirakata Y, Kondo A, Hoshino K et al. Efflux pump inhibitors reduce the invasiveness of Pseudomonas aeruginosa. Int. J. Antimicrob. Agents 34(4), 343-346 (2009).
64. Martinez JL, Rojo F. Metabolic regulation of antibiotic resistance. FEMS Microbiol. Rev. doi: 10.1111/j.1574-6976.2011.00282.x (2011) (Epub ahead of print). Analyzes the cross-talk between bacterial metabolism and antibiotic resistance.
65. Lewis K. Persister cells. Annu. Rev. Microbiol. 64, 357-372 (2010).
66. Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S. Bacterial persistence as a phenotypic switch. Science 305(5690), 1622-1625 (2004).
67. Levin BR, Rozen DE. Non-inherited antibiotic resistance. Nat. Rev. Microbiol. 4(7), 556-562 (2006).
68. Levin BR. Microbiology. Noninherited resistance to antibiotics. Science 305(5690), 1578-1579 (2004).
69. Allison KR, Brynildsen MP, Collins JJ. Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature 473(7346), 216-220 (2011). Describes a method for eliminating persister cells using specific metabolites and is a proof-of-concept on the possibility of enhancing antibiotic activity by rewiring the bacterial metabolism.
70. Kahan FM, Kahan JS, Cassidy PJ, Kropp H. The mechanism of action of fosfomycin (phosphonomycin). Ann. NY Acad. Sci. 235(0), 364-386 (1974).
71. Scortti M, Lacharme-Lora L, Wagner M, Chico-Calero I, Losito P, Vazquez-Boland JA. Coexpression of virulence and fosfomycin susceptibility in Listeria: molecular basis of an antimicrobial in vitro-in vivo paradox. Nat. Med. 12(5), 515-517 (2006). Describes that bacteria can present in vivo, a different phenotype of antibiotic susceptibility as found in vitro. In this case, bacteria are hypersusceptible when growing intracellularly.
72. Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA, Collins JJ. A common mechanism of cellular death induced by bactericidal antibiotics. Cell 130(5), 797-810 (2007). The authors propose a common antibiotic-induced cell-death pathway that may serve for defining new targets for obtaining novel antibiotics.
73. Kohanski MA, Dwyer DJ, Collins JJ. How antibiotics kill bacteria: from targets to networks. Nat. Rev. Microbiol. 8(6), 423-435 (2010).
74. Ginsberg AM. Drugs in development for tuberculosis. Drugs 70(17), 2201-2214 (2010).
75. Koul A, Arnoult E, Lounis N, Guillemont J, Andries K. The challenge of new drug discovery for tuberculosis. Nature 469(7331), 483-490 (2011).
76. Hinz A, Lee S, Jacoby K, Manoil C. Membrane proteases and aminoglycoside antibiotic resistance. J. Bacteriol. 193(18), 4790-4797 (2011).
77. Alekshun MN, Levy SB. Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon. Antimicrob. Agents Chemother. 41(10), 2067-2075 (1997).
78. Luong TT, Dunman PM, Murphy E, Projan SJ, Lee CY. Transcription profiling of the mgrA regulon in Staphylococcus aureus. J. Bacteriol. 188(5), 1899-1910 (2006).
79. Truong-Bolduc QC, Dunman PM, Strahilevitz J, Projan SJ, Hooper DC. MgrA is a multiple regulator of two new efflux pumps in Staphylococcus aureus. J. Bacteriol. 187(7), 2395-2405 (2005).
80. Martinez JL, Baquero F. Interactions among strategies associated with bacterial infection: pathogenicity, epidemicity, and antibiotic resistance. Clin. Microbiol. Rev. 15(4), 647-679 (2002).
81. Lee S, Hinz A, Bauerle E et al. Targeting a bacterial stress response to enhance antibiotic action. Proc. Natl Acad. Sci. USA 106(34), 14570-14575 (2009).
82. Linares JF, Moreno R, Fajardo A et al. The global regulator Crc modulates metabolism, susceptibility to antibiotics and virulence in Pseudomonas aeruginosa. Environ. Microbiol. 12, 3196-3212 (2010). Describes the effect of a global regulator of carbon metabolism on the resistance to antibiotics and the virulence of Pseudomonas aeruginosa.
83. MacGregor CH, Wolff JA, Arora SK, Phibbs PV Jr. Cloning of a catabolite repression control (Crc) gene from Pseudomonas aeruginosa, expression of the gene in Escherichia coli, and identification of the gene product in Pseudomonas aeruginosa. J. Bacteriol. 173(22), 7204-7212 (1991).
84. Morales G, Linares JF, Beloso A, Albar JP, Martinez JL, Rojo F. The Pseudomonas putida Crc global regulator controls the expression of genes from several chromosomal catabolic pathways for aromatic compounds. J. Bacteriol. 186(5), 1337-1344 (2004).
85. Moreno R, Martinez-Gomariz M, Yuste L, Gil C, Rojo F. The Pseudomonas putida Crc global regulator controls the hierarchical assimilation of amino acids in a complete medium: evidence from proteomic and genomic analyses. Proteomics 9(11), 2910-2928 (2009).
86. Moreno R, Marzi S, Romby P, Rojo F. The Crc global regulator binds to an unpaired A-rich motif at the Pseudomonas putida alkS mRNA coding sequence and inhibits translation initiation. Nucleic Acids Res. 37(22), 7678-7690 (2009).
87. Moreno R, Rojo F. The target for the Pseudomonas putida Crc global regulator in the benzoate degradation pathway is the BenR transcriptional regulator. J. Bacteriol. 190(5), 1539-1545 (2008).
88. Sonnleitner E, Abdou L, Haas D. Small RNA as global regulator of carbon catabolite repression in Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA 106(51), 21866-21871 (2009).
89. Fukuoka T, Ohya S, Narita T et al. Activity of the carbapenem panipenem and role of the OprD (D2) protein in its diffusion through the Pseudomonas aeruginosa outer membrane. Antimicrob. Agents Chemother. 37(2), 322-327 (1993).
90. Castaneda-Garcia A, Rodriguez-Rojas A, Guelfo JR, Blazquez J. The glycerol-3-phosphate permease GlpT is the only fosfomycin transporter in Pseudomonas aeruginosa. J. Bacteriol. 191(22), 6968-6974 (2009).
91. Hernandez A, Sanchez MB, Martinez JL. Quinolone resistance: much more than predicted. Frontiers in Microbiology 2, 22 (2011).
92. Maeda T, Garcia-Contreras R, Pu M et al. Quorum quenching quandary: resistance to antivirulence compounds. Isme J. (2011).
93. van Veen HW, Callaghan R, Soceneantu L, Sardini A, Konings WN, Higgins CF. A bacterial antibiotic-resistance gene that complements the human multidrug-resistance P-glycoprotein gene. Nature 391(6664), 291-295 (1998).
94. Neyfakh AA, Bidnenko VE, Chen LB. Efflux-mediated multidrug resistance in Bacillus subtilis: similarities and dissimilarities with the mammalian system. Proc. Natl Acad. Sci. USA 88(11), 4781-4785 (1991).
95. Sexton JZ, Wigle TJ, He Q et al. Novel inhibitors of E. coli RecA ATPase activity. Curr. Chem. Genomics 4, 34-42 (2010).
96. Wigle TJ, Sexton JZ, Gromova AV et al. Inhibitors of RecA activity discovered by high-throughput screening: cell-permeable small molecules attenuate the SOS response in Escherichia coli. J. Biomol. Screen 14(9), 1092-1101 (2009).
97. Wigle TJ, Singleton SF. Directed molecular screening for RecA ATPase inhibitors. Bioorg. Med. Chem. Lett. 17(12), 3249-3253 (2007).
98. Lee AM, Ross CT, Zeng BB, Singleton SF. A molecular target for suppression of the evolution of antibiotic resistance: inhibition of the Escherichia coli RecA protein by N(6)-(1-naphthyl)-ADP. J. Med. Chem. 48(17), 5408-5411 (2005).
99. Martinez JL, Baquero F, Andersson DI. Beyond serial passages: new methods for predicting the emergence of resistance to novel antibiotics. Curr. Opin. Pharmacol. 11(5), 439-445 (2011).
100. Macvanin M, Hughes D. Hyper-susceptibility of a fusidic acid-resistant mutant of Salmonella to different classes of antibiotics. FEMS Microbiol. Lett. 247(2), 215-220 (2005).
101. Macvanin M, Bjorkman J, Eriksson S, Rhen M, Andersson DI, Hughes D. Fusidic acid-resistant mutants of Salmonella enterica serovar Typhimurium with low fitness in vivo are defective in RpoS induction. Antimicrob. Agents Chemother. 47(12), 3743-3749 (2003).
102. Macvanin M, Johanson U, Ehrenberg M, Hughes D. Fusidic acid-resistant EF-G perturbs the accumulation of ppGpP. Mol. Microbiol. 37(1), 98-107 (2000).
103. Paulander W, Maisnier-Patin S, Andersson DI. The fitness cost of streptomycin resistance depends on rpsL mutation, carbon source and RpoS (sigmaS). Genetics 183(2), 539-546, 531SI-532SI (2009).
104. Wexselblatt E, Katzhendler J, Saleem-Batcha R et al. ppGpp analogues inhibit synthetase activity of Rel proteins from Gram-negative and Gram-positive bacteria. Bioorg. Med. Chem. 18(12), 4485-4497 (2010).
105. Anacor Pharmaceuticals www.anacor.com