Pharmacological Targeting of the Host–Pathogen Interaction: Alternatives to Classical Antibiotics to Combat Drug-Resistant Superbugs

Trends in Pharmacological Sciences

Volumn 38, Issue 5, 2017, Pages 473-488

  Munguia, Jason ^a   Nizet, Victor ^a,b,c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^c RADY CHILDREN'S HOSPITAL   (United States)

Author keywords

antibiotic resistance; bacterial infections; immunotherapy; macrophages; neutrophils; virulence factors

Indexed keywords

ANTIBIOTIC AGENT; BACTENECIN; CD131 ANTIGEN; CHEMOKINE; CYTOKINE; ERYTHROPOIETIN RECEPTOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMMUNOMODULATING AGENT; LEUKOTRIENE B4; MONOCLONAL ANTIBODY; PEPTIDE E; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 1; ANTIINFECTIVE AGENT;

ANTIBIOTIC RESISTANCE; BACTERIAL VIRULENCE; BACTERICIDAL ACTIVITY; BIOFILM; CANCER IMMUNOTHERAPY; CYSTIC FIBROSIS; DISEASE COURSE; DRUG MECHANISM; DRUG REPOSITIONING; DRUG TARGETING; GENE EXPRESSION; HOST PATHOGEN INTERACTION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; INNATE IMMUNITY; MACROPHAGE; MULTIDRUG RESISTANCE; NEUTROPHIL; NONHUMAN; PATHOGENESIS; PHAGOCYTE; REVIEW; STAPHYLOCOCCUS INFECTION; VIRUS NEUTRALIZATION; ANIMAL; BACTERIAL INFECTIONS; DRUG EFFECTS;

ANIMALS; ANTI-BACTERIAL AGENTS; ANTIBODIES, MONOCLONAL; BACTERIAL INFECTIONS; DRUG RESISTANCE, MULTIPLE; HOST-PATHOGEN INTERACTIONS; HUMANS;

EID: 85014437802     PISSN: 01656147     EISSN: 18733735     Source Type: Journal    
DOI: 10.1016/j.tips.2017.02.003     Document Type: Review

References (100)

1. 1 Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. O'Neill, J., (eds.), 2014, HM Government.
2. 2 Chan, M. (2016) WHO Director-General addresses UN General Assembly on antimicrobial resistance. Published online September 21, 2016. http://www.who.int/dg/speeches/2016/unga-antimicrobial-resistance/en/.
3. 3 Nizet, V., Stopping superbugs, maintaining the microbiota. Sci. Transl. Med., 7, 2015, 295ed8.
4. 4 Gustke, H., et al. Inhibition of the bacterial lectins of Pseudomonas aeruginosa with monosaccharides and peptides. Eur. J. Clin. Microbiol. Infect. Dis. 31 (2012), 207–215.
5. 5 Johansson, E.M., et al. Inhibition and dispersion of Pseudomonas aeruginosa biofilms by glycopeptide dendrimers targeting the fucose-specific lectin LecB. Chem Biol 15 (2008), 1249–1257.
6. 6 Cusumano, C.K., et al. Treatment and prevention of urinary tract infection with orally active FimH inhibitors. Sci. Transl. Med., 3, 2011, 109ra115.
7. 7 Oh, K.B., et al. Inhibition of sortase-mediated Staphylococcus aureus adhesion to fibronectin via fibronectin-binding protein by sortase inhibitors. Appl. Microbiol. Biotechnol. 70 (2006), 102–106.
8. 8 Oleksiewicz, M.B., et al. Anti-bacterial monoclonal antibodies: back to the future?. Arch Biochem Biophys 526 (2012), 124–131.
9. 9 Sause, W.E., et al. Antibody-based biologics and their promise to combat Staphylococcus aureus infections. Trends Pharmacol. Sci. 37 (2016), 231–241.
10. 10 Berube, B.J., Bubeck Wardenburg, J., Staphylococcus aureus alpha-toxin: nearly a century of intrigue. Toxins 5 (2013), 1140–1166.
11. 11 Inoshima, I., et al. A Staphylococcus aureus pore-forming toxin subverts the activity of ADAM10 to cause lethal infection in mice. Nat. Med. 17 (2011), 1310–1314.
12. 12 Ragle, B.E., Bubeck Wardenburg, J., Anti-alpha-hemolysin monoclonal antibodies mediate protection against Staphylococcus aureus pneumonia. Infect. Immun. 77 (2009), 2712–2718.
13. 13 Hua, L., et al. Assessment of an anti-alpha-toxin monoclonal antibody for prevention and treatment of Staphylococcus aureus-induced pneumonia. Antimicrob. Agents Chemother. 58 (2014), 1108–1117.
14. 14 Rouha, H., et al. Five birds, one stone: neutralization of alpha-hemolysin and 4 bi-component leukocidins of Staphylococcus aureus with a single human monoclonal antibody. MAbs 7 (2015), 243–254.
15. 15 Scully, I.L., et al. Demonstration of the preclinical correlate of protection for Staphylococcus aureus clumping factor A in a murine model of infection. Vaccine 33 (2015), 5452–5457.
16. 16 McAdow, M., et al. Preventing Staphylococcus aureus sepsis through the inhibition of its agglutination in blood. PLoS Pathog., 7, 2011, e1002307.
17. 17 Sawa, T., et al. Anti-PcrV antibody strategies against virulent Pseudomonas aeruginosa. Hum. Vaccin Immunother. 10 (2014), 2843–2852.
18. 18 Warrener, P., et al. A novel anti-PcrV antibody providing enhanced protection against Pseudomonas aeruginosa in multiple animal infection models. Antimicrob. Agents Chemother. 58 (2014), 4384–4391.
19. 19 Yamamoto, B.J., et al. Obiltoxaximab prevents disseminated Bacillus anthracis infection and improves survival during pre- and post-exposure prophylaxis in animal models of inhalational anthrax. Antimicrob. Agents Chemother. 60 (2016), 5796–5805.
20. 20 Anosova, N.G., et al. A combination of three fully human toxin A- and toxin B-specific monoclonal antibodies protects against challenge with highly virulent epidemic strains of Clostridium difficile in the hamster model. Clin. Vaccine Immunol. 22 (2015), 711–725.
21. 21 Lehar, S.M., et al. Novel antibody–antibiotic conjugate eliminates intracellular S. aureus. Nature 527 (2015), 323–328.
22. 22 McCormick, C.C., et al. Chemical inhibition of alpha-toxin, a key corneal virulence factor of Staphylococcus aureus. Invest. Ophthalmol. Vis. Sci. 50 (2009), 2848–2854.
23. 23 Ragle, B.E., et al. Prevention and treatment of Staphylococcus aureus pneumonia with a beta-cyclodextrin derivative. Antimicrob. Agents Chemother. 54 (2010), 298–304.
24. 24 Henry, B.D., et al. Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice. Nat. Biotechnol. 33 (2015), 81–88.
25. 25 Hu, C.M., et al. A biomimetic nanosponge that absorbs pore-forming toxins. Nat. Nanotechnol. 8 (2013), 336–340.
26. 26 Wang, F., et al. Hydrogel retaining toxin-absorbing nanosponges for local treatment of methicillin-resistant Staphylococcus aureus infection. Adv. Mater. 27 (2015), 3437–3443.
27. 27 Hu, C.M., et al. Nanoparticle biointerfacing by platelet membrane cloaking. Nature 526 (2015), 118–121.
28. 28 Basha, S., et al. Polyvalent inhibitors of anthrax toxin that target host receptors. Proc. Natl. Acad. Sci. U. S. A. 103 (2006), 13509–13513.
29. 29 Sampedro, G.R., et al. Targeting Staphylococcus aureus alpha-toxin as a novel approach to reduce severity of recurrent skin and soft-tissue infections. J. Infect. Dis. 210 (2014), 1012–1018.
30. 30 Gillespie, E.J., et al. Selective inhibitor of endosomal trafficking pathways exploited by multiple toxins and viruses. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), E4904–4912.
31. 31 Shoop, W.L., et al. Anthrax lethal factor inhibition. Proc. Natl. Acad. Sci. U. S. A. 102 (2005), 7958–7963.
32. 32 Bender, K.O., et al. A small-molecule antivirulence agent for treating Clostridium difficile infection. Sci. Transl. Med., 7, 2015, 306ra148.
33. 33 Gonzalez-Juarbe, N., Pore-forming toxins induce macrophage necroptosis during acute bacterial pneumonia. PLoS Pathog., 11, 2015, e1005337.
34. 34 Gilley, R.P., et al. Infiltrated macrophages die of pneumolysin-mediated necroptosis following pneumococcal myocardial invasion. Infect. Immun. 84 (2016), 1457–1469.
35. 35 Hung, D.T., et al. Small-molecule inhibitor of Vibrio cholerae virulence and intestinal colonization. Science 310 (2005), 670–674.
36. 36 Nait Chabane, Y., et al. Virstatin inhibits biofilm formation and motility of Acinetobacter baumannii. BMC Microbiol., 14, 2014, 62.
37. 37 Yang, J., et al. Disarming bacterial virulence through chemical inhibition of the DNA binding domain of an AraC-like transcriptional activator protein. J. Biol. Chem. 288 (2013), 31115–31126.
38. 38 Koppolu, V., et al. Small-molecule inhibitor of the Shigella flexneri master virulence regulator VirF. Infect. Immun. 81 (2013), 4220–4231.
39. 39 Parsons, J.B., et al. Perturbation of Staphylococcus aureus gene expression by the enoyl-acyl carrier protein reductase inhibitor AFN-1252. Antimicrob. Agents Chemother. 57 (2013), 2182–2190.
40. 40 Sun, H., et al. Inhibitor of streptokinase gene expression improves survival after group A streptococcus infection in mice. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 3469–3474.
41. 41 Kim, H.S., et al. 6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition. Sci. Rep., 5, 2015, 8656.
42. 42 O'Loughlin, C.T., et al. A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 17981–17986.
43. 43 Kasper, S.H., et al. Chemical inhibition of kynureninase reduces Pseudomonas aeruginosa quorum sensing and virulence factor expression. ACS Chem. Biol. 11 (2016), 1106–1117.
44. 44 Zhang, Y., et al. Inhibition of alpha-toxin production by subinhibitory concentrations of naringenin controls Staphylococcus aureus pneumonia. Fitoterapia 86 (2013), 92–99.
45. 45 Hendrix, A.S., et al. Repurposing the nonsteroidal anti-inflammatory drug diflunisal as an osteoprotective, anti-virulence therapy for Staphylococcus aureus osteomyelitis. Antimicrob. Agents Chemother. 60 (2016), 5322–5330.
46. 46 Goller, C.C., et al. Lifting the mask: identification of new small molecule inhibitors of uropathogenic Escherichia coli group 2 capsule biogenesis. PLoS One, 9, 2014, e96054.
47. 47 Sakoulas, G., et al. Nafcillin enhances innate immune-mediated killing of methicillin-resistant Staphylococcus aureus. J. Mol. Med. 92 (2014), 139–149.
48. 48 Kumaraswamy, M., et al. Standard susceptibility testing overlooks potent azithromycin activity and cationic peptide synergy against MDR Stenotrophomonas maltophilia. J. Antimicrob. Chemother. 71 (2016), 1264–1269.
49. 49 Lin, L., et al. Azithromycin synergizes with cationic antimicrobial peptides to exert bactericidal and therapeutic activity against highly multidrug-resistant Gram-negative bacterial pathogens. EBioMedicine 2 (2015), 690–698.
50. 50 Liu, G.Y., et al. Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity. J. Exp. Med. 202 (2005), 209–215.
51. 51 Liu, C.I., et al. A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence. Science 319 (2008), 1391–1394.
52. 52 Chen, F., et al. Small-molecule targeting of a diapophytoene desaturase inhibits S. aureus virulence. Nat. Chem. Biol. 12 (2016), 174–179.
53. 53 Mishra, N.N., et al. Carotenoid-related alteration of cell membrane fluidity impacts Staphylococcus aureus susceptibility to host defense peptides. Antimicrob. Agents Chemother. 55 (2011), 526–531.
54. 54 Reppe, K., et al. Immunostimulation with macrophage-activating lipopeptide-2 increased survival in murine pneumonia. Am. J. Respir Cell Mol. Biol. 40 (2009), 474–481.
55. 55 Kaplan, A., et al. Failure to induce IFN-beta production during Staphylococcus aureus infection contributes to pathogenicity. J. Immunol. 189 (2012), 4537–4545.
56. 56 Pasula, R., et al. Keratinocyte growth factor administration attenuates murine pulmonary mycobacterium tuberculosis infection through granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent macrophage activation and phagolysosome fusion. J. Biol. Chem. 290 (2015), 7151–7719.
57. 57 Wu, H., et al. Keratinocyte growth factor augments pulmonary innate immunity through epithelium-driven, GM-CSF-dependent paracrine activation of alveolar macrophages. J. Biol. Chem. 286 (2011), 14932–14940.
58. 58 Greenberger, M.J., Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumoniae. J. Immunol. 155 (1995), 722–729.
59. 59 Soares, E.M., et al. Leukotriene B4 enhances innate immune defense against the puerperal sepsis agent Streptococcus pyogenes. J. Immunol. 190 (2013), 1614–1622.
60. 60 Mancuso, P., et al. Intrapulmonary administration of leukotriene B4 enhances pulmonary host defense against pneumococcal pneumonia. Infect. Immun. 78 (2010), 2264–2271.
61. 4 augments neutrophil accumulation and responses in the lung to Klebsiella infection in CXCL1 knockout mice. J. Immunol. 188 (2012), 3458–3468.
62. 62 Ramon, S., et al. The protectin PCTR1 Is produced by human M2 macrophages and enhances resolution of infectious inflammation. Am. J. Pathol. 186 (2016), 962–973.
63. 63 Dalli, J., et al. Identification and actions of a novel third maresin conjugate in tissue regeneration: MCTR3. PLoS One, 11, 2016, e0149319.
64. 64 Winkler, J.W., et al. Resolvin D4 stereoassignment and its novel actions in host protection and bacterial clearance. Sci. Rep., 6, 2016, 18972.
65. 65 Dalli, J., et al. Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections. Nat. Med. 21 (2015), 1071–1075.
66. 66 Svahn, S.L., et al. Dietary omega-3 fatty acids increase survival and decrease bacterial load in mice subjected to Staphylococcus aureus-induced sepsis. Infect. Immun. 84 (2016), 1205–1213.
67. 67 Mancuso, P., et al. Disruption of leptin receptor–STAT3 signaling enhances leukotriene production and pulmonary host defense against pneumococcal pneumonia. J. Immunol. 186 (2011), 1081–1090.
68. 68 Peyssonnaux, C., et al. HIF-1alpha expression regulates the bactericidal capacity of phagocytes. J. Clin. Invest. 115 (2005), 1806–1815.
69. 69 Okumura, C.Y., et al. A new pharmacological agent (AKB-4924) stabilizes hypoxia inducible factor-1 (HIF-1) and increases skin innate defenses against bacterial infection. J. Mol. Med. 90 (2012), 1079–1089.
70. 70 Lin, A.E., et al. Role of hypoxia inducible factor-1alpha (HIF-1alpha) in innate defense against uropathogenic Escherichia coli infection. PLoS Pathog., 11, 2015, e1004818.
71. 71 Kyme, P., et al. C/EBPepsilon mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice. J. Clin. Invest. 122 (2012), 3316–3329.
72. 72 Abdulrahman, B.A., Autophagy stimulation by rapamycin suppresses lung inflammation and infection by Burkholderia cenocepacia in a model of cystic fibrosis. Autophagy 7 (2011), 1359–1370.
73. 73 van der Does, A.M., Antimicrobial peptide hLF1-11 directs granulocyte-macrophage colony-stimulating factor-driven monocyte differentiation toward macrophages with enhanced recognition and clearance of pathogens. Antimicrob. Agents Chemother. 54 (2010), 811–816.
74. 74 Bjorn, C., et al. Anti-infective efficacy of the lactoferrin-derived antimicrobial peptide HLR1r. Peptides 81 (2016), 21–28.
75. 75 Polgarova, K., et al. The erythropoietin analogue ARA290 modulates the innate immune response and reduces Escherichia coli invasion into urothelial cells. FEMS Immunol. Med. Microbiol. 62 (2011), 190–196.
76. 76 Nijnik, A., et al. Synthetic cationic peptide IDR-1002 provides protection against bacterial infections through chemokine induction and enhanced leukocyte recruitment. J. Immunol. 184 (2010), 2539–2550.
77. 77 Lembo, A., et al. Administration of a synthetic TLR4 agonist protects mice from pneumonic tularemia. J. Immunol. 180 (2008), 7574–7581.
78. 78 Munoz, N., et al. Mucosal administration of flagellin protects mice from Streptococcus pneumoniae lung infection. Infect. Immun. 78 (2010), 4226–4233.
79. 79 Krieg, A.M., et al. CpG DNA induces sustained IL-12 expression in vivo and resistance to Listeria monocytogenes challenge. J. Immunol. 161 (1998), 2428–2434.
80. 80 Elkins, K.L., et al. Bacterial DNA containing CpG motifs stimulates lymphocyte-dependent protection of mice against lethal infection with intracellular bacteria. J. Immunol. 162 (1999), 2291–2298.
81. 81 Raby, A.C., et al. Targeting the TLR co-receptor CD14 with TLR2-derived peptides modulates immune responses to pathogens. Sci. Transl. Med., 5, 2013, 185ra64.
82. 82 Napier, R.J., et al. Imatinib-sensitive tyrosine kinases regulate mycobacterial pathogenesis and represent therapeutic targets against tuberculosis. Cell Host Microbe. 10 (2011), 475–485.
83. 83 Bruns, H., et al. Abelson tyrosine kinase controls phagosomal acidification required for killing of Mycobacterium tuberculosis in human macrophages. J. Immunol. 189 (2012), 4069–4078.
84. 84 Chiu, H.C., et al. Eradication of intracellular Salmonella enterica serovar Typhimurium with a small-molecule, host cell-directed agent. Antimicrob. Agents Chemother. 53 (2009), 5236–5244.
85. 85 Chiu, H.C., et al. Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent. J. Biomed. Sci., 16, 2009, 110.
86. 86 Corriden, R., et al. Tamoxifen augments the innate immune function of neutrophils through modulation of intracellular ceramide. Nat. Commun., 6, 2015, 8369.
87. 87 Janda, S., et al. The effect of statins on mortality from severe infections and sepsis: a systematic review and meta-analysis. J. Crit. Care, 25, 2010 656.e7–656.e22.
88. 88 Chopra, V., et al. Is statin use associated with reduced mortality after pneumonia? A systematic review and meta-analysis. Am. J. Med. 125 (2012), 1111–1123.
89. 89 Graziano, T.S., et al. Statins and antimicrobial effects: simvastatin as a potential drug against Staphylococcus aureus biofilm. PLoS One, 10, 2015, e0128098.
90. 90 Thangamani, S., et al. Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent. Sci. Rep., 5, 2015, 16407.
91. 91 Hennessy, E., et al. Statins inhibit in vitro virulence phenotypes of Pseudomonas aeruginosa. J. Antibiot. 66 (2013), 99–101.
92. 92 Horn, M.P., et al. Simvastatin inhibits Staphylococcus aureus host cell invasion through modulation of isoprenoid intermediates. J. Pharmacol. Exp. Ther. 326 (2008), 135–143.
93. 93 Shibata, H., et al. Simvastatin represses translocation of Pseudomonas aeruginosa across Madin–Darby canine kidney cell monolayers. J. Med. Invest. 59 (2012), 186–191.
94. 94 Burnham, C.A., et al. Rac1, RhoA, and Cdc42 participate in HeLa cell invasion by group B streptococcus. FEMS Microbiol. Lett. 272 (2007), 8–14.
95. 95 Rosch, J.W., et al. Statins protect against fulminant pneumococcal infection and cytolysin toxicity in a mouse model of sickle cell disease. J. Clin. Invest. 120 (2010), 627–635.
96. 96 deCathelineau, A.M., Bokoch, G.M., Inactivation of rho GTPases by statins attenuates anthrax lethal toxin activity. Infect. Immun. 77 (2009), 348–359.
97. 97 Dechend, R., et al. Hydroxymethylglutaryl coenzyme A reductase inhibition reduces Chlamydia pneumoniae-induced cell interaction and activation. Circulation 108 (2003), 261–265.
98. 98 Erkkila, L., et al. Effect of simvastatin, an established lipid-lowering drug, on pulmonary Chlamydia pneumoniae infection in mice. Antimicrob. Agents Chemother. 49 (2005), 3959–3962.
99. 99 Parihar, S.P., et al. Simvastatin enhances protection against Listeria monocytogenes infection in mice by counteracting Listeria-induced phagosomal escape. PLoS One, 8, 2013, e75490.
100. 100 Chow, O.A., et al. Statins enhance formation of phagocyte extracellular traps. Cell Host Microbe. 8 (2010), 445–454.