Suppression of Staphylococcus aureus virulence by a small-molecule compound

Proceedings of the National Academy of Sciences of the United States of America

Volumn 115, Issue 31, 2018, Pages 8003-8008

  Gao, Peng ^a   Ho, Pak Leung ^a,b   Yan, Bingpeng ^a   Sze, Kong Hung ^a   Davies, Julian ^c   Kao, Richard Yi Tsun ^a,b  

^a UNIVERSITY OF HONG KONG   (Hong Kong)

^b THE UNIVERSITY OF HONG KONG   (Hong Kong)

^c UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Antivirulence; Bacterial infection; ClpP; MRSA; Virulence factors

Indexed keywords

CYCLOSPORIN A [4 LEUCINE]; ANTIINFECTIVE AGENT; BACTERIAL PROTEIN; ENDOPEPTIDASE CLP;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BACTEREMIA; BACTERIAL GENE; BACTERIAL VIRULENCE; CELL ADHESION; CONTROLLED STUDY; DIFFERENTIAL SCANNING FLUORIMETRY; FLUOROMETRY; GENE EXPRESSION; HIGH THROUGHPUT SCREENING; HLA GENE; HUMAN; HUMAN CELL; INTERNALIZATION; MOLECULAR MODEL; MOUSE; MOUSE MODEL; MUTAGENESIS; NONHUMAN; PRIORITY JOURNAL; PSM GENE; STAPHYLOCOCCUS AUREUS; WESTERN BLOTTING; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DISEASE MODEL; GENETICS; METABOLISM; PATHOGENICITY; PATHOLOGY; PROMOTER REGION; STAPHYLOCOCCUS INFECTION;

ANIMALS; ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; DISEASE MODELS, ANIMAL; ENDOPEPTIDASE CLP; MICE; PROMOTER REGIONS, GENETIC; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS;

EID: 85052321600     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1720520115     Document Type: Article

References (41)

1. Crossley KB (2010) Staphylococci in Human Disease (Wiley-Blackwell, Chichester, UK), 2nd Ed, p xii.
2. Lowy FD (2003) Antimicrobial resistance: The example of Staphylococcus aureus. J Clin Invest 111:1265–1273.
3. Blot SI, Vandewoude KH, Hoste EA, Colardyn FA (2002) Outcome and attributable mortality in critically Ill patients with bacteremia involving methicillin-susceptible and methicillin-resistant Staphylococcus aureus. Arch Intern Med 162:2229–2235.
4. Peacock SJ, et al. (2002) Virulent combinations of adhesin and toxin genes in natural populations of Staphylococcus aureus. Infect Immun 70:4987–4996.
5. Pozzi C, et al. (2017) Vaccines for Staphylococcus aureus and target populations. Curr Top Microbiol Immunol 409:491–528.
6. Escaich S (2008) Antivirulence as a new antibacterial approach for chemotherapy. Curr Opin Chem Biol 12:400–408.
7. Cegelski L, Marshall GR, Eldridge GR, Hultgren SJ (2008) The biology and future prospects of antivirulence therapies. Nat Rev Microbiol 6:17–27.
8. Gordon CP, Williams P, Chan WC (2013) Attenuating Staphylococcus aureus virulence gene regulation: A medicinal chemistry perspective. J Med Chem 56:1389–1404.
9. Stevens DL, et al. (2007) Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus. J Infect Dis 195:202–211.
10. Uddin R, Lodhi MU, Ul-Haq Z (2012) Combined pharmacophore and 3D-QSAR study on a series of Staphylococcus aureus Sortase A inhibitors. Chem Biol Drug Des 80: 300–314.
11. Liu CI, et al. (2008) A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence. Science 319:1391–1394.
12. Gao P, Davies J, Kao RYT (2017) Dehydrosqualene desaturase as a novel target for anti-virulence therapy against Staphylococcus aureus. MBio 8:e01224-17.
13. Sun F, et al. (2011) Targeting MgrA-mediated virulence regulation in Staphylococcus aureus. Chem Biol 18:1032–1041.
14. McCormick CC, Caballero AR, Balzli CL, Tang A, O’Callaghan RJ (2009) Chemical inhibition of alpha-toxin, a key corneal virulence factor of Staphylococcus aureus. Invest Ophthalmol Vis Sci 50:2848–2854.
15. Alonzo F, 3rd, et al. (2013) CCR5 is a receptor for Staphylococcus aureus leukotoxin ED. Nature 493:51–55.
16. Gao J, Stewart GC (2004) Regulatory elements of the Staphylococcus aureus protein A (Spa) promoter. J Bacteriol 186:3738–3748.
17. Cheng AG, et al. (2009) Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues. FASEB J 23:3393–3404.
18. Stranger-Jones YK, Bae T, Schneewind O (2006) Vaccine assembly from surface proteins of Staphylococcus aureus. Proc Natl Acad Sci USA 103:16942–16947.
19. Reyes-Robles T, et al. (2013) Staphylococcus aureus leukotoxin ED targets the chemokine receptors CXCR1 and CXCR2 to kill leukocytes and promote infection. Cell Host Microbe 14:453–459.
20. Powers ME, Becker RE, Sailer A, Turner JR, Bubeck Wardenburg J (2015) Synergistic action of Staphylococcus aureus α-Toxin on platelets and myeloid lineage cells contributes to lethal sepsis. Cell Host Microbe 17:775–787.
21. Torres VJ, et al. (2007) A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence. Cell Host Microbe 1:109–119.
22. Michel A, et al. (2006) Global regulatory impact of ClpP protease of Staphylococcus aureus on regulons involved in virulence, oxidative stress response, autolysis, and DNA repair. J Bacteriol 188:5783–5796.
23. Frees D, Gerth U, Ingmer H (2014) Clp chaperones and proteases are central in stress survival, virulence and antibiotic resistance of Staphylococcus aureus. Int J Med Microbiol 304:142–149.
24. Gao P, et al. (2016) Construction of a multiplex promoter reporter platform to monitor Staphylococcus aureus virulence gene expression and the identification of usnic acid as a potent suppressor of psm gene expression. Front Microbiol 7:1344.
25. Kao RY, et al. (2004) Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics. Chem Biol 11: 1293–1299.
26. Feng J, et al. (2013) Trapping and proteomic identification of cellular substrates of the ClpP protease in Staphylococcus aureus. J Proteome Res 12:547–558.
27. Geiger SR, Böttcher T, Sieber SA, Cramer P (2011) A conformational switch underlies ClpP protease function. Angew Chem Int Ed Engl 50:5749–5752.
28. Frees D, et al. (2012) New insights into Staphylococcus aureus stress tolerance and virulence regulation from an analysis of the role of the ClpP protease in the strains Newman, COL, and SA564. J Proteome Res 11:95–108.
29. Gersch M, List A, Groll M, Sieber SA (2012) Insights into structural network responsible for oligomerization and activity of bacterial virulence regulator caseinolytic protease P (ClpP) protein. J Biol Chem 287:9484–9494.
30. Rasko DA, Sperandio V (2010) Anti-virulence strategies to combat bacteria-mediated disease. Nat Rev Drug Discov 9:117–128.
31. Löffler B, et al. (2010) Staphylococcus aureus panton-valentine leukocidin is a very potent cytotoxic factor for human neutrophils. PLoS Pathog 6:e1000715.
32. Anderson MJ, et al. (2012) Alpha-toxin promotes Staphylococcus aureus mucosal biofilm formation. Front Cell Infect Microbiol 2:64.
33. Schwartz K, Syed AK, Stephenson RE, Rickard AH, Boles BR (2012) Functional amyloids composed of phenol soluble modulins stabilize Staphylococcus aureus biofilms. PLoS Pathog 8:e1002744.
34. Kao RY, et al. (2004) Characterization of SARS-CoV main protease and identification of biologically active small molecule inhibitors using a continuous fluorescence-based assay. FEBS Lett 576:325–330.
35. Kao RY, et al. (2010) Identification of influenza A nucleoprotein as an antiviral target. Nat Biotechnol 28:600–605.
36. Frees D, Qazi SN, Hill PJ, Ingmer H (2003) Alternative roles of ClpX and ClpP in Staphylococcus aureus stress tolerance and virulence. Mol Microbiol 48:1565–1578.
37. Frees D, et al. (2004) Clp ATPases are required for stress tolerance, intracellular replication and biofilm formation in Staphylococcus aureus. Mol Microbiol 54:1445–1462.
38. Chatterjee I, et al. (2005) Staphylococcus aureus ClpC is required for stress resistance, aconitase activity, growth recovery, and death. J Bacteriol 187:4488–4496.
39. Frees D, Sørensen K, Ingmer H (2005) Global virulence regulation in Staphylococcus aureus: Pinpointing the roles of ClpP and ClpX in the sar/agr regulatory network. Infect Immun 73:8100–8108.
40. Böttcher T, Sieber SA (2008) Beta-lactones as specific inhibitors of ClpP attenuate the production of extracellular virulence factors of Staphylococcus aureus. J Am Chem Soc 130:14400–14401.
41. Pahl A, et al. (2015) Reversible inhibitors arrest ClpP in a defined conformational state that can be revoked by ClpX association. Angew Chem Int Ed Engl 54:15892–15896.