Can virulence factors be viable antibacterial targets?

Expert Review of Anti-Infective Therapy

Volumn 2, Issue 1, 2004, Pages 61-72

  Marra, Andrea ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

In vivo screens; In vivo targets; Pathogenesis; Surrogate models; Virulence targets

Indexed keywords

ANTIBIOTIC AGENT; ANTIINFECTIVE AGENT; REAGENT; VIRULENCE FACTOR;

ANTIBIOTIC RESISTANCE; BACTERIAL INFECTION; BACTERIAL VIRULENCE; CROSS RESISTANCE; DNA MICROARRAY; DRUG CLASSIFICATION; DRUG INDUSTRY; DRUG TARGETING; HEALTH CARE; HOST CELL; HUMAN; NONHUMAN; REVIEW;

EID: 2942555442     PISSN: 14787210     EISSN: None     Source Type: Journal    
DOI: 10.1586/14787210.2.1.61     Document Type: Review

References (103)

1. Cazzola M, Matera MG, Page CP. Novel approaches to the treatment of pneumonia. Trends Pharmacol. Sci. 24(6), 306-314 (2003).
2. Projan SJ. New (and not so new) antibacterial targets - from where and when will the novel drugs come? Curr. Opin. Pharmacol. 2, 513-522 (2002).
3. Aballay A, Ausubel FM. Caenorhabditis elegans as a host for the study of host-pathogen interactions. Curr. Opin. Microbiol. 5, 97-101 (2002).
4. Dionne MS, Ghori N, Schneider DS. Drosophila melanogaster is a genetically tractable model host for Mycobacterium marinum. Infect. Immun 71(6), 3540-3550 (2003).
5. D'Argenio DA, Gallagher LA, Berg CA, Manoil C. Drosophila as a model host for Pseudomonas aeruginosa infection. J. Bacteriology 183(4), 1466-1471 (2001).
6. Jander G, Rahme LG, Ausubel FM. Positive correlation between virulence of Pseudomonas aeruginosa mutants in mice and insects. J. Bacteriol. 182(13), 3843-3845 (2000).
7. Kaito C, Akimitsu N, Watanabe H, Sekimizu K. Silkworm larvae as an animal model of bacterial infection pathogenic to humans. Microb. Pathog. 32(4), 183-190 (2002).
8. Mahajan-Miklos S, Rahme LG, Ausubel FM. Elucidating the molecular mechanisms of bacterial virulence using nonmammalian hosts. Mol. Microbiol. 37(5), 981-988 (2000).
9. Kurz CL, Chauvet S, Andres E et al. Virulence factors of the human opportunistic pathogen Serratia marcescens identified by in vivo screening. EMBO J. 22(7), 1451-1460 (2003).
10. Garsin DA, Sifri CD, Mylonakis E et al. A simple model host for identifying Gram-positive virulence factors. Proc. Natl Acad. Sci. 98(19), 10892-10897 (2001).
11. Sifri CD, Begun J, Ausubel FM, Calderwood SB. Caenorhabditis elegans as a model host for Staphyloccus aureus pathogenesis. Infect. Immun 71(4), 2208-2217 (2003).
12. Alegado RA, Campbell MC, Chen WC, Slutz SS, Tan M-W. Characterization of mediators of microbial virulence and innate immunity using the Caenorhabditis elegans host-pathogen model. Cell. Microbiol. 5(7), 435-444 (2003).
13. Lemaitre B, Reichhart J-M, Hoffmann JA. Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms. Proc. Natl Acad. Sci. 94, 14614-14619 (1997).
14. Tzou P, de Gregorio F, Lemaitre B. How Drosophila combats microbial infection: a model to study innate immunity and host-pathogen interactions. Curr. Opin. Microbiol. 5, 102-110 (2002).
15. Kurz CL, Ewbank JJ. Caenorhabditis elegans: an emerging genetic model for the study of innate immunity. Nature Rev. Genet. 4, 380-390 (2003).
16. Leulier F, Parquet C, Pili-Floury S et al. The Drosophila immune system detects bacteria through specific peptidoglycan recognition. Nature Immunol. 4(5), 478-484 (2003).
17. Buer J, Balling R. Mice, microbes and models of infection. Nature Rev. Genet. 4, 195-205 (2003).
18. Opperman T, Ling LL, Moir DT. Microbial pathogen genomes - new strategies for identifying therapeutic and vaccine targets. Expert Opin. Ther. Targets 7(4), 469-473 (2003).
19. Hensel M, Shea JE, Gleeson C et al. Simultaneous identification of bacterial virulence genes by negative selection. Science 269, 400-403 (1995).
20. Perry RD. Signature-tagged mutagenesis and the hunt for virulence factors. Trends Microbiol. 7(10) 385-388 (1999).
21. Shea JE, Santagelo JD, Feldman RG. Signature-tagged mutagenesis in the identification of virulence genes in pathogens. Curr. Opin. Microbiol. 3, 451-458 (2000).
22. Lehoux DE, Levesque RC. Detection of genes essential in specific niches by signature-tagged mutagenesis. Curr. Opin. Biotechnol. 11, 434-439 (2000).
23. Chiang SL, Mekalanos JJ, Holden DW. In vivo genetic analysis of bacterial virulence. Ann. Rev. Microbiol. 53, 129-154 (1999).
24. Polissi A, Pontiggia A, Feger G et al. Large-scale identification of virulence genes from Streptococcus pneumoniae. Infect. Immun 66(12), 5620-5629 (1998).
25. Lau GW, Haataja S, Lonetto M et al. A functional genomic analysis of Type 3 Streptococcus pneumoniae virulence. Mol. Microbiol. 40(3), 555-571 (2001).
26. Hava DL, Camilli A. large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors. Mol. Microbiol. 45(5), 1389-1405 (2002).
27. Mecsas J. Use of signature-tagged mutagenesis in pathogenesis studies. Curr. Opin. Microbiol. 5, 33-37 (2002).
28. Coulter SN, Schwan WR, Ng EY et al. Staphylococcus aureus genetic loci impacting growth and survival in multiple infection environments. Mol. Microbiol. 30(2), 393-404 (1998).
29. Angelichio MJ, Camilli A. In vivo expression technology. Infect. Immun.. 70(12), 6518-6523 (2002).
30. Rankin S, Isberg R. Identification of Legionella pneumophila promoters regulated by the macrophage intracellular environment. Infect. Agents Dis. 2(4), 269-271 (1993).
31. Rankin S, Li Z, Isberg RR. Macrophage-induced genes of Legionella pneumophila: protection from reactive intermediates and solute imbalance during intracellular growth. Infect. Immun 70(7), 3637-3648 (2002).
32. Mahan MJ, Slauch JM, Mekalanos JJ. Selection of bacterial virulence genes that are specifically induced in host tissues. Science 259, 686-688 (1993).
33. Mahan MJ, Tobias JW, Slauch JM, Hanna PC, Collier RJ. Antibiotic-based selection for bacterial genes that are specifically induced during infection of a host. Proc. Natl Acad. Sci. 92, 669-673 (1995).
34. Kiliç A, Herzberg M, Meyer M, Zhao Z, Tao L. Streptococcal reporter gene-fusion vector for identification of in vivo expressed genes. Plasmid 42(1), 67-72 (1999).
35. Camilli A, Beattie DT, Mekalanos JJ. Use of genetic recombination as a reporter of gene expression. Proc. Natl Acad. Sci. 91, 2634-2638 (1994).
36. Camilli A, Mekalanos J. Use of recombinase gene fusions to identify Vibrio cholerae genes induced during infection. Mol. Microbiol. 18, 671-683 (1995).
37. Lee S, Butler S, Camilli A. Selection for in vivo regulators of bacterial virulence. Proc. Natl Acad. Sci. 98(12), 6889-6894 (2001).
38. Marra A, Asundi J, Bartilson M et al. Differential fluorescence induction analysis of Streptococcus pneumoniae identifies genes involved in pathogenesis. Infect. Immun 70(3), 1422-1433 (2002).
39. Badger J, Wass C, Kim K. Identification of Escherichia coli K1 genes contributing to human brain microvascular endothelial cell invasion by differential fluorescence induction. Mol. Microbiol. 36(1), 174-182 (2000).
40. Schneider WP, Ho SK, Christine J et al. Virulence gene indentification by differential fluorescence induction analysis of Staphylococcus aureus gene expression during infection-simulating culture. Infect. Immun 70(3), 1326-1333 (2002).
41. Valdivia RH, Falkow S. Bacterial genetics by flow cytometry: rapid isolation of Salmonella typhimurium acid-inducible promoters by differential fluorescence induction. Mol. Microbiol. 22(2), 367-378 (1996).
42. Mason KM, Munson RS, Jr., Bakaletz LO. Nontypeable Haemophilus influenzae gene expression induced in vivo in a chinchilla model of otitis media. Infect. Immun 71(6), 3454-3462 (2003).
43. Cummings CA, Relman DA. Using DNA microarrays to study host-microbe interactions. Emer. Infect. Dis. 6(5), 513-525 (2000).
44. Kato-Maeda M, Gao Q, Small PM. Microarray analyis of pathogens and their interactions with hosts. Cell. Microbiol. 3(11), 713-719 (2001).
45. Haney SA, Alksne LE, Dunman PM, Murphy E, Projan SJ. Genomics in anti-infective drug discovery - getting to endgame. Curr. Pharmaceutical Design 8, 1099-1118 (2002).
46. Sassetti C, Rubin EJ. Genomic analyses of microbial virulence. Curr. Opin. Microbiol. 5, 27-32 (2002).
47. Deb DK, Dahiya P, Srivastava KK, Srivastava R, Srivastava BS. Selective identification of new therpeutic targets of Mycobacterium tuberculosis by IVIAT approach. Tuberculosis (Edinb.) 82(4-5), 175-82 (2002).
48. Kim YR, Lee SE, Kim CM et al. Characterization and pathogenic significance of Vibrio vulnificus antigens preferentially expressed in septicemic patients. Infect. Immun 71(10), 5461-5471 (2003).
49. Etz H, Minh DB, Henics T et al. Identification of in vivo expressed vaccine candidate antigens ftom Staplylococcus aureus. Proc. Natl Acad. Sci. 99(10), 6573-6578 (2002).
50. Hang L, John M, Asaduzzaman M et al. Use of in vivo-induced antigen technology (IVIAT) to identify genes uniquely expressed during human infection with Vibrio cholerae. Proc. Natl Acad. Sci. 100(14), 8508-8513 (2003).
51. Wizemann TM, Heinrichs JH, Adamou JE et al. Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae. Infect. Immun 69(3), 1593-1598 (2001).
52. Li Y, Frey E, Mackenzie AMR, Finlay BB. Human response to Escherichia coli 0157:H7 infection: antibodies to secreted virulence factors. Infect. Immun 68(9), 5090-5095 (2000).
53. Kernodle DS, Voladri RKP, Menzies BE, Hager CC, Edwards KM. Expresison of antisense hla fragment in Staphylococcus aureus reduces alpha-toxin production in vitro and attentuates lethal activity in a murine model. Infect. Immun 65(1), 179-184 (1997).
54. Ji Y, Marra A, Rosenberg M, Woodnutt G. Regulated antisense RNA eliminates alpha-toxin virulence in Staphylococcus aureus infection. J. Bacteriol. 181(21), 6585-6590 (1999).
55. Ji Y, Zhang B, Van Horn SF et al. Identification of critical staphylococcal genes using conditional phenotypes generated by antisense RNA. Science 293, 2266-2269 (2001).
56. Macielag M, Goldschmidt R. Inhibitors of bacterial two-component signalling systems. Expert Opin. Invest. Drug 9(10), 2351-2369 (2000).
57. Barrett JF, Goldschmidt RM, Lawrence LE et al. Antibacterial agents that inhibit two-component signal transduction systems. Proc. Natl Acad. Sci. 95, 5317-5322 (1998).
58. Barrett JF, Hoch JA. Two-component signal transduction as a target for microbial anti-infective therapy. Antimicrob. Agents Chemother. 42(7), 1529-1536 (1998).
59. Wallis NG. Bacterial two-component signal transduction systems as drug targets. Curr. Opin. Anti-infect. Invest. Drugs 1(4), 428-434 (1999).
60. Stephenson K, Hoch JA. Virulence- and antibiotic resistance-associated two-component signal transduction systems of Gram-positive pathogenic bacteria as targets for antimicrobial therapy. Pharmacol. Ther. 93, 293-305 (2002).
61. Throup JP, Koretke KK, Bryant AP et al. A genomic analysis of two-component signal transduction in Streptococcus pneumoniae. Mol. Microbiol. 35(3), 566-576 (2000).
62. Blue CE, Mitchell TJ. Contribution of a response regulator to the virulence of Streptococcus pneumoniae is strain dependent. Infect. Immun 71(8), 4405-4413 (2003).
63. Panthel K, Dietz P, Haas R, Beier D. Two-component systems of Helicobacter pylori contribute to virulence in a mouse infection model. Infect. Immun 71(9), 5381-5385 (2003).
64. Kreikemeyer B, McIver KS, Podbielski A. Virulence factor regulation and regulatory networks in Streptococcus pyogenes and their impact on pathogen-host interactions. Trends Microbiol. 11(5), 224-232 (2003).
65. Parish T, Smith DA, Kendall S et al. Deletion of two-component regulatory systems increases the virulence of Mycobacterium tuberculosis. Infect. Immun 71(3), 1134-1140 (2003).
66. Hueck C. Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol. Mol. Biol. Rev. 62, 379-433 (1998).
67. Muller S, Feldman MF, Cornelis GR. The Type III secretion system of Gram-negative bacteria: a potential therapeutic target. Expert Opin. Ther. Targets 5(3), 327-339 (2001).
68. Winstanley C, Hart CA. Type III secretion systems and pathogenicity islands. J. Med. Microbiol. 50, 116-126 (2001).
69. Miyata S, Casey M, Frank DW, Ausubel FM, Drenkard E. Use of the Galleria mellonella caterpillar as a model host to study the role of the Type III secretion system in Pseudomonas aeruginosa pathogenesis. Infect. Immun 71 (5), 2402-2413 (2003).
70. Kauppi AM, Nordfelth R, Uvell H, Wolf-Watz H, Elofsson M. Targeting bacterial virulence: inhibitors of Type III secretion in Yersinia. Chem. Biol. 10, 241-249 (2003).
71. Donlan R, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin. Microbiol. Rev. 15(2), 167-193 (2002).
72. Dunne WM Jr. Bacterial adhesion: seen any good biofilms lately? Clin. Microbiol. Rev. 15(2), 155-166 (2002).
73. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science 284, 1318-1322 (1999).
74. Ehrlich GD, Veeh R, Wang X et al. Mucosal biofilm formation on middle-ear mucosa in the chinchilla model of otitis media. J. Am. Med. Assoc. 287(13), 1710-1715 (2002).
75. Davies D. Understanding biofilm resistance to antibacterial agents. Nature Reviews Drug Discovery 2, 114-122 (2003).
76. Leid JG, Shirtliff ME, Costerton JW, Stoodley P. Human leukocytes adhere to, penetrate and respond to Staphylococcus aureus biofilms. Infect. Immun 70(11), 6339-6345 (2002).
77. Murphy TF, Kirkham C. Biofilm formation by nontypeable Haemophilus influenzae: strain variability, outer membrane antigen expression and role of pili. BMC Microbiol. 2, 7-15 (2002).
78. Schembri MA, Kjaergaard K, Klemm P. Global gene expression in Escherichia coli biofilms. Mol. Microbiol. 480(1), 253-267 (2003).
79. Hentzer M, Eberl L, Nielsen J, Givskov M. Quorum sensing: a novel target for the treatment of biofilm infections. Biodrugs 17(4), 241-250 (2003).
80. Camara M, Williams P, Hardman A. Controlling infection by tuning in and turning down the volume of bacterial small-talk. Lancet Infect. Dis. 2, 667-676 (2002).
81. Wu H, Song Z, Hentzer M et al. Detection of N-acylhomoserine lactones in lung tissues of mice infected with Pseudomonas aeruginosa. Microbiol. 146, 2481-2493 (2000).
82. Ward C, Camara M, Forrest I et al. Preliminary findings of quorum signal molecules in clinically stable lung allograft recipients. Thorax 58, 444-446 (2003).
83. Hentzer M, Riedel K, Rasmussen TB et al. Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiol. 148, 87-102 (2002).
84. Hentzer M, Wu H, Anderson JB et al. Attentuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J. 22(15), 3803-3815 (2003).
85. Bassler BL, Greenberg EP, Stevens AM. Cross-species induction of luminescence in the quorum-sensing bacterium Vibrio harveyi. J. Bacteriol. 179(12), 4043-4045 (1997).
86. Ji G, Beavis RC, Novick RP. Bacterial interference caused by autoinducing peptide variants. Science 276, 2027-2030 (1997).
87. Balaban N, Goldkorn T, Nhan RT et al. Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureus. Science 280, 438-440 (1998).
88. Hartman G, Wise R. Quorum sensing: potential means of treating Gram-negative infections? Lancet 351, 848-849 (1998).
89. Bauer WB, Robinson JB. Disruption of bacterial quorum sensing by other organisms. Curr. Opin. Biotech. 13(3), 234-237 (2002).
90. Balaban N, Giacometti A, Cirioni O et al. Use of the quroum-sensing inhibitor RNAIII-inhibiting peptide to prevent biofilm formation in vivo by drug-resistant Staplylococcus epidermidis. J. Infect. Dis. 187, 625-630 (2003).
91. Dong Y-H, Wang L-H, Xu J-L et al. Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase. Nature 411, 813-817 (2001).
92. Finch RG, Pritchard DI, Bycroft BW, Williams P, Stewart GSAB. Quorum sensing: a novel target for anti-infective therapy. J. Antimicrob. Chemotber. 42, 569-571 (1998).
93. Winzer K, Williams P. Quorum sensing and the regulation of virulence gene expression in pathogenic bacteria. Int. J. Med. Microbiol. 291, 131-143 (2001).
94. Williams P. Quorum sensing: an emerging target for antibacterial chemotherapy? Expert Opin. Ther. Targets 6(3), 257-274 (2002).
95. Kohler T, Van Delden C, Curry LK, Hamzehpour MM, Pechere J-C. Overexpression of the MexEF-OprN multidrug efflux system affects cell-to-cell signalling in Pseudomonas aeruginosa. J. Bacteriol. 183(18), 5213-5222 (2001).
96. Sanchez P, Linares JF, Ruiz-Diez B et al. Fitness of in vitro selected Pseudomonas aeruginosa nalB and nfxB multidrug resistant mutants. J. Antimicrob. Chemother. 50, 657-664 (2002).
97. Hirakata Y, Srikumar R, Poole K et al. Multidrug efflux systems play an important role in the invasiveness of Pseudomonas aeruginosa. J. Exp. Med. 196(1), 109-118 (2002).
98. Rahmati S, Yang S, Davidson AL, Zechiedrich EL. Control of the AcrAB multidrug efflux pump by quorum-sensing regulator SdiA. Mol. Microbiol. 43(3), 677-685 (2002).
99. Smith JN, Ahmer BMM. Detection of other microbial species by Salmonella: expression of the SdiA regulon. J. Bacteriol. 185(4), 1357-1366 (2003).
100. Chang S, Sievert DM, Hageman JC et al. Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene. N. Engl. J. Med. 348(14), 1342-1347 (2003).
101. Goldschmidt R, Macielag M, Hlasta D, Barrett J. Inhibition of virulence factors in bacteria. Curr. Pharm. Design 3 125-142 (1997).
102. Alksne LE. Virulence as a target for antimicrobial chemotherapy. Expert Opin. Invest. Drugs 11(8), 1149-1159 (2002).
103. Coates A, Hu Y, Bax R, Page C. The future challenges facing the development of new antimicrobial drugs. Nature Reviews Drug Discovery 1, 895-910 (2002).