Novel strategies to combat bacterial virulence

Current Opinion in Critical Care

Volumn 14, Issue 5, 2008, Pages 593-599

  Lynch, Susan V ^a   Wiener Kronish, Jeanine R ^a,b,c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Antimicrobial therapy; Bacterial virulence; Novel therapeutics; Quorum sensing; Type iii secretion system

Indexed keywords

ANTIBIOTIC AGENT; ANTIFOULING AGENT; BOTULINUM TOXIN ANTIBODY; C 30; C 56; FURANONE DERIVATIVE; GALLIUM; HAMAMELITANNIN; IRON; LCRV ANTIBODY; METICILLIN; PCRV ANTIBODY; PROTEIN ANTIBODY; QUINOLINIC ACID; UNCLASSIFIED DRUG; VALORTIM; VIRULENCE FACTOR;

ACCLIMATIZATION; ADVERSE OUTCOME; ANTHRAX; ANTIBIOTIC RESISTANCE; ANTIBIOTIC THERAPY; BACILLUS ANTHRACIS; BACTERIAL IMMUNITY; BACTERIAL INFECTION; BACTERIAL VIRULENCE; BACTERIUM ADHERENCE; BIODIVERSITY; BURKHOLDERIA CEPACIA; CANDIDA ALBICANS; CELL COMMUNICATION; CLINICAL PRACTICE; CLINICAL TRIAL; CLOSTRIDIUM DIFFICILE; DRUG EFFICACY; DRUG HALF LIFE; ESCHERICHIA COLI; FOOD AND DRUG ADMINISTRATION; GENE EXPRESSION; HUMAN; IMMUNE RESPONSE; IMMUNOGENICITY; IRON TRANSPORT; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MICROBIAL COMMUNITY; NONHUMAN; OXIDATION REDUCTION REACTION; PHAGOCYTOSIS; PLAGUE; PSEUDOMONAS AERUGINOSA; QUORUM SENSING; REGULATORY MECHANISM; REVIEW; SERRATIA LIQUEFACIENS; SHIGELLA; STAPHYLOCOCCUS EPIDERMIDIS; SUPERINFECTION; YERSINIA PESTIS;

ANTI-BACTERIAL AGENTS; BACTERIAL INFECTIONS; CRITICAL CARE; DRUG RESISTANCE, BACTERIAL; HUMANS; QUORUM SENSING; VIRULENCE;

EID: 55349148374     PISSN: 10705295     EISSN: 15317072     Source Type: Journal    
DOI: 10.1097/MCC.0b013e32830f1dd5     Document Type: Review

References (66)

1. Sears CL. A dynamic partnership: celebrating our gut flora. Anaerobe 2005; 11:247-251.
2. Roy-Burman A, Savel RH, Racine S, et al. Type III protein secretion is associated with death in lower respiratory and systemic Pseudomonas aeruginosa infections. J Infect Dis 2001; 183:1767-1774.
3. Finck-Barbancon V, Goranson J, Zhu L, et al. ExoU expression by Pseudomonas aeruginosa correlates with acute cytotoxicity and epithelial injury. Mol Microbiol 1997; 25:547-557.
4. Kurahashi K, Kajikawa O, Sawa T, et al. Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. J Clin Invest 1999; 104:743-750.
5. Pankhaniya RR, Tamura M, Allmond LR, et al. Pseudomonas aeruginosa causes acute lung injury via the catalytic activity of the patatin-like phospholipase domain of ExoU. Crit Care Med 2004; 32:2293-2299.
6. Dacheux D, Toussaint B, Richard M, et al. Pseudomonas aeruginosa cystic fibrosis isolates induce rapid, type III secretion-dependent, but ExoU-independent, oncosis of macrophages and polymorphonuclear neutrophils. Infect Immun 2000; 68:2916-2924.
7. Geddes K, Cruz F, Heffron F. Analysis of cells targeted by Salmonella type III secretion in vivo. PLoS Pathog 2007; 3:e196.
8. Broz P, Mueller CA, Muller SA, et al. Function and molecular architecture of the Yersinia injectisome tip complex. Mol Microbiol 2007; 65:1311-1320.
9. Faure K, Fujimoto J, Shimabukuro DW, et al. Effects of monoclonal anti-PcrV antibody on Pseudomonas aeruginosa-induced acute lung injury in a rat model. J Immune Based Ther Vaccines 2003; 1:2.
10. Frank DW, Vallis A, Wiener-Kronish JP, et al. Generation and characterization of a protective monoclonal antibody to Pseudomonas aeruginosa PcrV. J Infect Dis 2002; 186:64-73.
11. Imamura Y, Yanagihara K, Fukuda Y, et al. Effect of anti-PcrV antibody in a murine chronic airway Pseudomonas aeruginosa infection model. Eur Respir J 2007; 29:965-968.
12. Neely AN, Holder IA, Wiener-Kronish JP, Sawa T. Passive anti-PcrV treatment protects burned mice against Pseudomonas aeruginosa challenge. Burns 2005; 31:153-158.
13. Sawa T, Yahr TL, Ohara M, et al. Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury. Nat Med 1999; 5:392-398.
14. Cornells GR, Wolf-Watz H. The Yersinia Yop virulon: a bacterial system for subverting eukaryotic cells. Mol Microbiol 1997; 23:861-867.
15. Brubaker RR. lnterleukin-10 and inhibition of innate immunity to Yersiniae: roles of Yops and LcrV (V antigen). Infect Immun 2003; 71:3673-3681.
16. Zauberman A, Cohen S, Levy Y, et al. Neutralization of Yersinia pestismediated macrophage cytotoxicity by anti-LcrV antibodies and its correlation with protective immunity in a mouse model of bubonic plague. Vaccine 2008; 26:1616-1625.
17. (SEC). USaEC. Pharmathene, Inc. Form 10-Q, Quarter Ended September 30, Commission File Number 001-32587. SEC web site [online], 2007. http://wwwsecgov/Archives/edgar/data/1326190/000110465907083136/ a07-29212_110qhtm#Item2_103948.
18. Lam J, Chan R, Lam K, Costerton JW. Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis. Infect Immun 1980; 28:546-556.
19. Guina T, Purvine SO, Yi EC, et al. Quantitative proteomic analysis indicates increased synthesis of a quinolone by Pseudomonas aeruginosa isolates from cystic fibrosis airways. Proc Natl Acad Sci U S A 2003; 100:2771-2776.
20. Hassett DJ, Cuppoletti J, Trapnell B, et al. Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa biofilms in chronically infected cystic fibrosis airways: rethinking antibiotic treatment strategies and drug targets. Adv Drug Deliv Rev 2002; 54:1425-1443.
21. Yoon SS, Hennigan RF, Hilliard GM, et al. Pseudomonas aeruginosa anaerobic respiration in biofilms: relationships to cystic fibrosis pathogenesis. Dev Cell 2002; 3:593-603.
22. Opal SM. Communal living by bacteria and the pathogenesis of urinary tract infections. PLoS Med 2007; 4:e349.
23. Wright KJ, Seed PC, Hultgren SJ. Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili. Cell Microbiol 2007; 9:2230-2241.
24. Yu L, Lee KK, Paranchych W, et al. Use of synthetic peptides to confirm that the Pseudomonas aeruginosa PAK pilus adhesin and the Candida albicans fimbrial adhesin possess a homologous receptor-binding domain. Mol Microbiol 1996; 19:1107-1116.
25. Lee KK, Yu L, Macdonald DL, et al. Antiadhesin antibodies that recognize a receptor-binding motif (adhesintope) inhibit pilus/fimbrial-mediated adherence of Pseudomonas aeruginosa and Candida albicans to asialo-GM1 receptors and human buccal epithelial cell surface receptors. Can J Microbiol 1996; 42:479-486.
26. Martinez JJ, Mulvey MA, Schilling JD, et al. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. EMBO J 2000; 19:2803-2812.
27. Garofalo CK, Hooton TM, Martin SM, et al. Escherichia col! from urine of female patients with urinary tract infections is competent for intracellular bacterial community formation. Infect Immun 2007; 75:52-60.
28. Sauer FG, Mulvey MA, Schilling JD, et al. Bacterial pili: molecular mechanisms of pathogenesis. Curr Opin Microbiol 2000; 3:65-72.
29. Manetti AG, Zingaretti C, Falugi F, et al. Streptococcus pyogenes pili promote pharyngeal cell adhesion and biofilm formation. Mol Microbiol 2007; 64:968-983.
30. Pan YT, Xu B, Rice K, et al. Specificity of the high-mannose recognition site between Enterobacter cloacae pili adhesin and HT-29 cell membranes. Infect Immun 1997; 65:4199-4206.
31. Firon N, Ashkenazi S, Mirelman D, et al. Aromatic alpha-glycosides of mannose are powerful inhibitors of the adherence of type 1 fimbriated Escherichia coli to yeast and intestinal epithelial cells. Infect Immun 1987; 55:472-476.
32. Hyland RM, Griener TP, Mulvey GL, et al. Basis for N-acetyllactosamine-mediated inhibition of enteropathogenic Escherichia coli localized adherence. J Med Microbiol 2006; 55 (Pt 6):669-675.
33. Hakkarainen J, Toivanen M, Leinonen A, et al. Human and bovine milk oligosaccharides inhibit Neisseria meningitidis pili attachment in vitro. J Nutr 2005; 135:2445-2448.
34. Sharon N. Carbohydrates as future antiadhesion drugs for infectious diseases. Biochim Biophys Acta 2006; 1760:527-537.
35. Aberg V, Almqvist F. Filicides-small molecules targeting bacterial virulence. Org Biomol Chem 2007; 5:1827-1834.
36. Larsson A, Johansson SM, Pinkner JS, et al. Multivariate design, synthesis, and biological evaluation of peptide inhibitors of FimC/FimH protein-protein interactions in uropathogenic Escherichia coli. J Med Chem 2005; 48:935-945.
37. Pinkner JS, Remaut H, Buelens F, et al. Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria. Proc Natl Acad Sci U S A 2006; 103:17897-17902.
38. Svensson A, Larsson A, Emtenas H, et al. Design and evaluation of pilicides: potential novel antibacterial agents directed against uropathogenic Escherichia coli. Chembiochem 2001; 2:915-918.
39. Prunier AL, Schuch R, Fernandez RE, et al. nadA and nadB of Shigella flexneri 5a are antivirulence loci responsible for the synthesis of quinolinate, a small molecule inhibitor of Shigella pathogenicity. Microbiology 2007; 153 (Pt 7): 2363-2372.
40. Hung DT, Shakhnovich EA, Pierson E, Mekalanos JJ. Small-molecule inhibitor of Vibrio cholerae virulence and intestinal colonization. Science 2005; 310:670-674. A high-throughput, phenotypic screen identified a small molecule 4-[N-(1,8-naphthalimide)]-n-butyric acid, virstatin. Virstatin inhibits the transcriptional regulator ToxT of V. cholerae preventing expression of both the cholera toxin and the toxin coregulated pilus. Administration of virstatin protected infant mice from intestinal colonization by V. cholerae.
41. Panchal RG, Hermone AR, Nguyen TL, et al. Identification of small molecule inhibitors of anthrax lethal factor. Nat Struct Mol Biol 2004; 11:67-72.
42. Tonello F, Seveso M, Marin O, et al. Screening inhibitors of anthrax lethal factor. Nature 2002; 418:386.
43. Turk BE, Wong TY, Schwarzenbacher R, et al. The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor. Nat Struct Mol Biol 2004; 11:60-66.
44. Sanchez AM, Thomas D, Gillespie EJ, et al. Amiodarone and bepridil inhibit anthrax toxin entry into host cells. Antimicrob Agents Chemother 2007; 51:2403-2411. Cell-based assay to identify new molecules that inhibit anthrax toxin resulted in identification of two potent antitoxic compounds, amiodarone and bepridil. Both drugs act by blocking endosomal acidification, thereby preventing anthrax toxin entry. Lethal toxin-challenged mice exhibited greater survival when treated with amiodarone.
45. Nordfelth R, Kauppi AM, Norberg HA, et al. Small-molecule inhibitors specifically targeting type III secretion. Infect Immun 2005; 73:3104-3114.
46. Carty NL, Layland N, Colmer-Hamood JA, et al. RxR modulates the expression of QS-controlled virulence factors in the Pseudomonas aeruginosa strain PAO1. Mol Microbiol 2006; 61:782-794.
47. Huber B, Riedel K, Hentzer M, et al. The cep quorum-sensing system of Burkholderia cepacia H111 controls biofilm formation and swarming motility. Microbiology 2001; 147 (Pt 9):2517-2528.
48. Lynch MJ, Swift S, Kirke DF, et al. The regulation of biofilm development by quorum sensing in Aeromonas hydrophila. Environ Microbiol 2002; 4:18-28.
49. Sakuragi Y, Kolter R. Quorum-sensing regulation of the biofilm matrix genes (pel) of Pseudomonas aeruginosa. J Bacteriol 2007; 189:5383-5386.
50. de Nys RW, A.D., König M, Sticher O. New halogenated furanones from the marine alga Delisea pulchra. Tetrahedron 1993; 49:11213-11220.
51. Hentzer M, Wu H, Andersen JB, et al. Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBOJ 2003; 22:3803-3815.
52. Wu H, Song Z, Hentzer M, et al. Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice. J Antimicrob Chemother 2004; 53:1054-1061.
53. Bjarnsholt T, Jensen PO, Rasmussen TB, et al. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections. Microbiology 2005; 151 (Pt 12):3873-3880.
54. Rasmussen TB, Skindersoe ME, Bjarnsholt T, et al. Identity and effects of quorum-sensing inhibitors produced by Penicillium species. Microbiology 2005; 151 (Pt 5):1325-1340.
55. Kiran MD, Adikesavan NV, Cirioni O, et al. Discovery of a quorum sensing inhibitor of drug resistant staphylococcal infections by structure-based virtual screening. Mol Pharmacol 2008; 73:1578-1586. In-silico screening of peptide analogues from a library of 300 000 molecules using the Integrated Scientific Information System (ISIS) software (Elsevier MDL, San Ramon, USA) led to the identification of a compound, hamamelitannin. This small nonpeptide molecule effectively blocks a quorum-sensing regulator and prevents infection by methicillin-resistant Staphylococcus species.
56. Augustin DK, Song Y, Baek MS, et al. Presence or absence of lipopolysaccharide O antigens affects type III secretion by Pseudomonas aeruginosa. J Bacteriol 2007; 189:2203-2209.
57. Riedel K, Hentzer M, Geisenberger O, et al. N-acylhomoserine- lactone-mediated communication between Pseudomonas aeruginosa and Burkholderia cepacia in mixed biofilms. Microbiology 2001; 147 (Pt 12):3249-3262.
58. Holden MT, Ram ChhabraS, de NysR, et al. Quorum-sensing crosstalk: isolation and chemical characterization of cyclic dipeptides from Pseudomonas aeruginosa and other gram-negative bacteria. Mol Microbiol 1999; 33:1254-1266.
59. Kaneko Y, Thoendel M, Olakanmi O, et al. The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and anti-biofilm activity. J Clin Invest 2007; 117:877-888. Use of gallium to elicit molecular subterfuge. P. aeruginosa relies on iron to regulate expression of a number of important virulence genes. Gallium, which is similar in ionic radius and charge is taken up by the bacterial cell but, unlike iron, fails to induce bacterial gene expression, resulting in inhibition of P. aeruginosa growth and biofilm formation in vitro.
60. Harris JK, De Groote MA, Sagel SD, et al. Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis. Proc Natl Acad Sci U S A 2007; 104:20529-20533.
61. Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science 2005; 308:1635-1638.
62. Ley RE, Backhed F, Turnbaugh P, et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 2005; 102:11070-11075.
63. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 2006; 444:1022-1023.
64. Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444:1027-1031.
65. Flanagan JL, Brodie EL, Weng L, et al. Loss of bacterial diversity during antibiotic treatment of intubated patients colonized with Pseudomonas aeruginosa. J Clin Microbiol 2007; 45:1954-1962.
66. Halsey J. Current and future treatment modalities for Clostridium difficile-associated disease. Am J Health Syst Pharm 2008; 65:705-715.