What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?

Trends in Microbiology

Volumn 22, Issue 12, 2014, Pages 676-685

  Painter, Kimberley L ^a   Krishna, Aishwarya ^a   Wigneshweraraj, Sivaramesh ^a   Edwards, Andrew M ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Accessory gene regulator; Antibiotic resistance; Bacteremia; Bloodstream infection; Quorum sensing; Staphylococcus

Indexed keywords

ANTIBIOTIC AGENT; BETA LACTAM ANTIBIOTIC; METICILLIN; OXACILLIN; PENICILLIN BINDING PROTEIN 2A; STAPHYLOCOCCUS TOXIN; VANCOMYCIN; VIRULENCE FACTOR; AGR PROTEIN, STAPHYLOCOCCUS AUREUS; BACTERIAL PROTEIN; TRANSACTIVATOR PROTEIN;

ACCESSORY GENE REGULATOR; AGR OPERON; ANTIBIOTIC RESISTANCE; BACTERIAL CHROMOSOME; BACTERIAL CLEARANCE; BACTERIAL COLONIZATION; BACTERIAL ENDOCARDITIS; BACTERIAL GENE; BACTERIAL TRANSMISSION; BACTERIAL VIRULENCE; BACTERIUM CARRIER; BIOFILM; BLOODSTREAM INFECTION; HUMAN; IMMUNE EVASION; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS INFECTION; METHICILLIN SUSCEPTIBLE STAPHYLOCOCCUS AUREUS; NEUTROPHIL; NONHUMAN; OPERON; PHAGOCYTOSIS; QUORUM SENSING; REVIEW; STAPHYLOCOCCAL BACTEREMIA; TYPE II STAPHYLOCOCCAL CASSETTE CHROMOSOME MEC; TYPE IV STAPHYLOCOCCAL CASSETTE CHROMOSOME MEC; VANCOMYCIN INTERMEDIATE STAPHYLOCOCCUS AUREUS; BACTEREMIA; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MICROBIOLOGY; PATHOGENICITY; PHYSIOLOGY; REGULATOR GENE; STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS INFECTION;

STAPHYLOCOCCUS; STAPHYLOCOCCUS AUREUS;

BACTEREMIA; BACTERIAL PROTEINS; DRUG RESISTANCE, BACTERIAL; GENE EXPRESSION REGULATION, BACTERIAL; GENES, REGULATOR; NEUTROPHILS; QUORUM SENSING; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS; TRANS-ACTIVATORS; VIRULENCE FACTORS;

EID: 84922789867     PISSN: 0966842X     EISSN: 18784380     Source Type: Journal    
DOI: 10.1016/j.tim.2014.09.002     Document Type: Review

References (100)

1. Fowler V.G., et al. Clinical identifiers of complicated Staphylococcus aureus bacteremia. Arch. Intern. Med. 2003, 163:2066-2072.
2. Edwards A.M., Massey R.C. How does Staphylococcus aureus escape the bloodstream?. Trends Microbiol. 2011, 19:184-190.
3. Kaasch A.J., et al. Staphylococcus aureus bloodstream infection: a pooled analysis of five prospective, observational studies. J. Infect. 2014, 68:242-251.
4. Chong Y.P., et al. Persistent Staphylococcus aureus bacteremia: a prospective analysis of risk factors, outcomes, and microbiologic and genotypic characteristics of isolates. Medicine (Baltimore) 2013, 92:98-108.
5. Hsu M.S., et al. Sequential time to positivity of blood cultures can be a predictor of prognosis of patients with persistent Staphylococcus aureus bacteremia. Clin. Microbiol. Infect. 2014, 10.1111/1469-0691.12608.
6. Park S.Y., et al. agr Dysfunction and persistent methicillin-resistant Staphylococcus aureus bacteremia in patients with removed eradicable foci. Infection 2013, 41:111-119.
7. Foster T.J., et al. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat. Rev. Microbiol. 2014, 12:49-62.
8. Otto M. Staphylococcus aureus toxins. Curr. Opin. Microbiol. 2014, 17:32-37.
9. Priest N.K., et al. From genotype to phenotype: can systems biology be used to predict Staphylococcus aureus virulence?. Nat. Rev. Microbiol. 2012, 10:791-797.
10. Traber K.E., et al. agr function in clinical Staphylococcus aureus isolates. Microbiology 2008, 154:2265-2274.
11. Gao W., et al. Two novel point mutations in clinical Staphylococcus aureus reduce linezolid susceptibility and switch on the stringent response to promote persistent infection. PLoS Pathog. 2010, 6:e1000944.
12. Harris S.R., et al. Whole-genome sequencing for analysis of an outbreak of methicillin-resistant Staphylococcus aureus: a descriptive study. Lancet Infect. Dis. 2013, 13:130-136.
13. Laabei M., et al. Predicting the virulence of MRSA from its genome sequence. Genome Res. 2014, 24:839-849.
14. Novick R.P., Geisinger E. Quorum sensing in staphylococci. Annu. Rev. Genet. 2008, 42:541-564.
15. Cheung G.Y., et al. Role of the accessory gene regulator agr in community-associated methicillin-resistant Staphylococcus aureus pathogenesis. Infect. Immun. 2011, 79:1927-1935.
16. Kobayashi S.D., et al. Comparative analysis of USA300 virulence determinants in a rabbit model of skin and soft tissue infection. J. Infect. Dis. 2011, 204:937-941.
17. Broderick A.H., et al. Surface coatings that promote rapid release of peptide-based AgrC inhibitors for attenuation of quorum sensing in Staphylococcus aureus. Adv. Healthc. Mater. 2014, 3:97-105.
18. Murray E.J., et al. Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors. J. Med. Chem. 2014, 57:2813-2819.
19. Nielsen A., et al. Solonamide B inhibits quorum sensing and reduces Staphylococcus aureus mediated killing of human neutrophils. PLoS Pathog. 2014, 9:e84992.
20. Sully E.K., et al. Selective chemical inhibition of agr quorum sensing in Staphylococcus aureus promotes host defence with minimal impact on resistance. PLoS Pathog. 2014, 10:e1004174.
21. Fournier B. Global regulators of Staphylococcus aureus virulence genes. Staphylococcus: molecular genetics 2008, 131-183. Caister Academic Press. J.A. Lindsay (Ed.).
22. Queck S.Y., et al. RNAIII-independent target gene control by the agr quorum-sensing system: insight into the evolution of virulence regulation in Staphylococcus aureus. Mol. Cell 2008, 32:150-158.
23. Wang L., et al. New insight into transmembrane topology of Staphylococcus aureus histidine kinase AgrC. Biochim. Biophys. Acta 2014, 1838:988-993.
24. Wang B., et al. Activation and inhibition of the receptor histidine kinase AgrC occurs through opposite helical transduction motions. Mol. Cell 2014, 53:929-940.
25. Roux A., et al. CodY-mediated regulation of the Staphylococcus aureus Agr system integrates nutritional and population density signals. J. Bacteriol. 2014, 196:1184-1196.
26. Fowler V.G., et al. Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein. J. Infect. Dis. 2004, 190:1140-1149.
27. Moise P., et al. Genotypic and phenotypic relationships among methicillin-resistant Staphylococcus aureus from three multicentre bacteremia studies. J. Antimicrob. Chemother. 2009, 63:873-876.
28. Shopsin B., et al. Mutations in agr do not persist in natural populations of methicillin-resistant Staphylococcus aureus. J. Infect. Dis. 2010, 202:1593-1599.
29. Butterfield J.M., et al. Predictors of agr dysfunction in methicillin-resistant Staphylococcus aureus (MRSA) isolates among patients with MRSA bloodstream infections. Antimicrob. Agents Chemother. 2011, 55:5433-5437.
30. Harigaya Y., et al. Characterization of heterogeneous vancomycin-intermediate resistance, MIC and accessory gene regulator (agr) dysfunction among clinical bloodstream isolates of Staphyloccocus aureus. BMC Infect. Dis. 2011, 11:287.
31. Schweizer M.L., et al. Increased mortality with accessory gene regulator (agr) dysfunction in Staphylococcus aureus among bacteremic patients. Antimicrob. Agents Chemother. 2011, 55:1082-1087.
32. Viedma E., et al. Relationship between agr dysfunction and reduced vancomycin susceptibility in methicillin-susceptible Staphylococcus aureus causing bacteremia. J. Antimicrob. Chemother. 2013, 69:51-58.
33. Traber K., Novick R. A slipped-mispairing mutation in AgrA of laboratory strains and clinical isolates results in delayed activation of agr and failure to translate δ- and α-hemolysins. Mol. Microbiol. 2006, 59:1519-1530.
34. Shopsin B., et al. Prevalence of agr dysfunction among colonizing Staphylococcus aureus strains. J. Infect. Dis. 2008, 198:1171-1174.
35. Smyth D.S., et al. Nasal carriage as a source of agr-defective Staphylococcus aureus bacteremia. J. Infect. Dis. 2012, 206:1168-1177.
36. Seidl K., et al. Relationship of agr expression and function with virulence and vancomycin treatment outcomes in experimental endocarditis due to methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 2011, 55:5631-5639.
37. Pynnonen M., et al. Hemoglobin promotes Staphylococcus aureus nasal colonization. PLoS Pathog. 2011, 7:e1002104.
38. Chong Y.P., et al. Accessory gene regulator (agr) dysfunction in Staphylococcus aureus bloodstream isolates from South Korean patients. Antimicrob. Agents Chemother. 2013, 57:1509-1512.
39. Massey R.C., et al. The evolution and maintenance of virulence in Staphylococcus aureus: a role for host-to-host transmission?. Nat. Rev. Microbiol. 2006, 4:953-958.
40. Moise P., et al. Vancomycin in vitro bactericidal activity and its relationship to efficacy in clearance of methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob. Agents Chemother. 2007, 51:2582-2586.
41. Malachowa N., et al. Global changes in Staphylococcus aureus gene expression in human blood. PLoS ONE 2011, 6:e18617.
42. Peterson M.M., et al. Apolipoprotein B is an innate barrier against invasive Staphylococcus aureus infection. Cell Host Microbe 2008, 4:555-566.
43. Hall P.R., et al. Nox2 modification of LDL is essential for optimal apolipoprotein B-mediated control of agr type III Staphylococcus aureus quorum-sensing. PLoS Pathog. 2013, 9:e1003166.
44. James E.H., et al. Transcriptional downregulation of agr expression in Staphylococcus aureus during growth in human serum can be overcome by constitutively active mutant forms of the sensor kinase AgrC. FEMS Microbiol. Lett. 2013, 349:153-162.
45. Rothfork J.M., et al. Fibrinogen depletion attenuates Staphyloccocus aureus infection by preventing density-dependent virulence gene up-regulation. J. Immunol. 2003, 171:5389-5395.
46. Surewaard B.G.J., et al. Inactivation of staphylococcal phenol soluble modulins by serum lipoprotein particles. PLoS Pathog. 2012, 8:e1002606.
47. Diep B.A., et al. Contribution of Panton-Valentine leukocidin in community-associated methicillin-resistant Staphylococcus aureus pathogenesis. PLoS ONE 2008, 3:e3198.
48. DuMont A., Nygaard T. Characterization of a new cytotoxin that contributes to Staphylococcus aureus pathogenesis. Mol. Microbiol. 2011, 79:814-825.
49. Edwards A.M., et al. Staphylococcus aureus host cell invasion and virulence in sepsis is facilitated by the multiple repeats within FnBPA. PLoS Pathog. 2010, 6:e1000964.
50. Edwards A.M., et al. Staphylococcus aureus extracellular adherence protein triggers TNFα release, promoting attachment to endothelial cells via protein A. PLoS ONE 2012, 7:e43046.
51. Pantrangi M., et al. Staphylococcal superantigen-like genes, ssl5 and ssl8, are positively regulated by Sae and negatively by Agr in the Newman strain. FEMS Microbiol. Lett. 2010, 308:175-184.
52. Bestebroer J., et al. Staphylococcal SSL5 inhibits leukocyte activation by chemokines and anaphylatoxins. Blood 2009, 113:328-337.
53. Bestebroer J., et al. Functional basis for complement evasion by staphylococcal superantigen-like 7. Cell. Microbiol. 2010, 12:1506-1516.
54. Benson M.A., et al. Staphylococcus aureus regulates the expression and production of the staphylococcal superantigen-like secreted proteins in a Rot-dependent manner. Mol. Microbiol. 2011, 81:659-675.
55. Armstrong P.C., et al. Staphylococcal superantigen-like protein 5 induces thrombotic and bleeding complications in vivo: inhibition by an anti-SSL5 antibody and the glycan Bimosiamose. J. Thromb. Haemost. 2012, 10:2607-2609.
56. Bardoel B.W., et al. Evasion of Toll-like receptor 2 activation by staphylococcal superantigen-like protein 3. J. Mol. Med. 2012, 90:1109-1120.
57. Spaan A.N., et al. Neutrophils versus Staphylococcus aureus: a biological tug of war. Annu. Rev. Microbiol. 2013, 67:629-650.
58. Schwartz J., et al. Neutrophil bleaching of GFP-expressing staphylococci: probing the intraphagosomal fate of individual bacteria. J. Immunol. 2009, 183:2632-2641.
59. Rothfork J.M., et al. Inactivation of a bacterial virulence pheromone by phagocyte-derived oxidants: new role for the NADPH oxidase in host defense. Proc. Natl. Acad. Sci. U.S.A. 2004, 101:13867-13872.
60. Shompole S., et al. Biphasic intracellular expression of Staphylococcus aureus virulence factors and evidence for Agr-mediated diffusion sensing. Mol. Microbiol. 2003, 49:919-927.
61. Carnes E.C., et al. Confinement-induced quorum sensing of individual Staphylococcus aureus bacteria. Nat. Chem. Biol. 2010, 6:41-45.
62. Pang Y.Y., et al. agr-Dependent interactions of Staphylococcus aureus USA300 with human polymorphonuclear neutrophils. J. Innate Immun. 2010, 2:546-559.
63. Voyich J.M., et al. Insights into mechanisms used by Staphylococcus aureus to avoid destruction by human neutrophils. J. Immunol. 2005, 175:3907-3919.
64. Sun F., et al. Quorum-sensing agr mediates bacterial oxidation response via an intramolecular disulfide redox switch in the response regulator AgrA. Proc. Natl. Acad. Sci. U.S.A. 2012, 109:9095-9100.
65. Geiger T., et al. The stringent response of Staphylococcus aureus and its impact on survival after phagocytosis through the induction of intracellular PSMs expression. PLoS Pathog. 2012, 8:e1003016.
66. Alonzo F., et al. Staphylococcus aureus leucocidin ED contributes to systemic infection by targeting neutrophils and promoting bacterial growth in vivo. Mol. Microbiol. 2012, 83:423-435.
67. DuMont A.L., et al. Staphylococcus aureus elaborates leukocidin AB to mediate escape from within human neutrophils. Infect. Immun. 2013, 81:1830-1841.
68. Alonzo F., Torres V.J. The bicomponent pore-forming leucocidins of Staphylococcus aureus. Microbiol. Mol. Biol. Rev. 2014, 78:199-230.
69. Surewaard B.G.J., et al. Staphylococcal alpha-phenol soluble modulins contribute to neutrophil lysis after phagocytosis. Cell. Microbiol. 2013, 15:1427-1437.
70. White M.J., et al. Phosphatidylinositol-specific phospholipase C contributes to survival of Staphylococcus aureus USA300 in human blood and neutrophils. Infect. Immun. 2014, 82:1559-1571.
71. Wang R., et al. Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat. Med. 2007, 13:1510-1514.
72. Otto M. Community-associated MRSA: what makes them special?. Int. J. Med. Microbiol. 2013, 303:324-330.
73. Kobayashi S.D., et al. Rapid neutrophil destruction following phagocytosis of Staphylococcus aureus. J. Innate Immun. 2010, 2:560-575.
74. Cheung G.Y., et al. Production of an attenuated phenol-soluble modulin variant unique to the MRSA clonal complex 30 increases severity of bloodstream infection. PLoS Pathog. 2014, 10:e1004298.
75. Sakoulas G., et al. Accessory gene regulator (agr) locus in geographically diverse Staphylococcus aureus isolates with reduced susceptibility to vancomycin. Antimicrob. Agents Chemother. 2002, 46:1492-1502.
76. McAleese F., et al. Overexpression of genes of the cell wall stimulon in clinical isolates of Staphylococcus aureus exhibiting vancomycin-intermediate- S. aureus-type resistance to vancomycin. J. Bacteriol. 2006, 188:1120-1133.
77. Howden B.P., et al. Different bacterial gene expression patterns and attenuated host immune responses are associated with the evolution of low-level vancomycin resistance during persistent methicillin-resistant Staphylococcus aureus bacteremia. BMC Microbiol. 2008, 8:39.
78. Collins J., et al. Identification of factors contributing to T-cell toxicity of Staphylococcus aureus clinical isolates. J. Clin. Microbiol. 2008, 46:2112-2114.
79. Collins J., et al. Offsetting virulence and antibiotic resistance costs by MRSA. ISME J. 2010, 4:577-584.
80. Moise P.A., et al. Factors influencing time to vancomycin-induced clearance of nonendocarditis methicillin-resistant Staphylococcus aureus bacteremia: role of platelet microbicidal protein killing and agr genotypes. J. Infect. Dis. 2010, 201:233-240.
81. Jang H.C., et al. Difference in agr dysfunction and reduced vancomycin susceptibility between MRSA bacteremia involving SCCmec types IV/IVa and I-III. PLoS ONE 2012, 7:e49136.
82. Rudkin J.K., et al. Methicillin resistance reduces the virulence of healthcare-associated methicillin-resistant Staphylococcus aureus by interfering with the agr quorum sensing system. J. Infect. Dis. 2012, 205:798-806.
83. Pozzi C., et al. Methicillin resistance alters the biofilm phenotype and attenuates virulence in Staphylococcus aureus device-associated infections. PLoS Pathog. 2012, 8:e1002626.
84. Rudkin J.K., et al. Oxacillin alters the toxin expression profile of community-associated methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 2014, 58:1100-1107.
85. Diekema D.J., et al. Continued emergence of USA300 methicillin-resistant Staphylococcus aureus in the United States: results from a nationwide surveillance study. Infect. Control Hosp. Epidemiol. 2014, 35:285-292.
86. Howden B.P., et al. The evolution of vancomycin intermediate Staphylococcus aureus (VISA) and heterogenous-VISA. Infect. Genet. Evol. 2014, 21:575-582.
87. Tsuji B.T., et al. Evaluation of accessory gene regulator (agr) group and function in the proclivity towards vancomycin intermediate resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 2007, 51:1089-1091.
88. Khatib R., et al. Persistent Staphylococcus aureus bacteremia: incidence and outcome trends over time. Scand. J. Infect. Dis. 2009, 41:4-9.
89. Park S., et al. Defects in innate immunity predispose C57BL/6J-Leprdb/Leprdb mice to infection by Staphylococcus aureus. Infect. Immun. 2009, 77:1008-1014.
90. Tseng C.W., et al. Innate immune dysfunctions in aged mice facilitate the systemic dissemination of methicillin-resistant S. aureus. PLoS ONE 2012, 7:e41454.
91. Chambers H.F., Deleo F.R. Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat. Rev. Microbiol. 2009, 7:629-641.
92. Goerke C., et al. Direct quantitative transcript analysis of the agr regulon of Staphylococcus aureus during human infection in comparison to the expression profile in vitro. Infect. Immun. 2000, 68:1304-1311.
93. Boles B.R., Horswill A.R. Agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog. 2008, 4:e1000052.
94. Wesson C.A., et al. Staphylococcus aureus Agr and Sar global regulators influence internalization and induction of apoptosis. Infect. Immun. 1998, 66:5238-5243.
95. Tuchscherr L., et al. Staphylococcus aureus phenotype switching: an effective bacterial strategy to escape host immune response and establish a chronic infection. EMBO Mol. Med. 2011, 3:129-141.
96. Pader V., et al. The Agr quorum-sensing system regulates fibronectin-binding but not hemolysis in the absence of a functional electron transport chain. Infect. Immun. 2014, 10.1128/IAI.02254-14.
97. Pollitt E.J., et al. Cooperation, quorum sensing, and evolution of virulence in Staphylococcus aureus. Infect. Immun. 2014, 82:1045-1051.
98. Laabei M., et al. Staphylococcus aureus interaction with phospholipid vesicles - a new method to accurately determine accessory gene regulator (agr) activity. PLoS ONE 2014, 9:e87270.
99. Cuirolo A., et al. Development of homogeneous expression of resistance in methicillin-resistant Staphylococcus aureus clinical strains is functionally associated with a beta-lactam-mediated SOS response. J. Antimicrob. Chemother. 2009, 64:37-45.
100. Rossi F., et al. Transferable vancomycin resistance in a community-associated MRSA lineage. N. Engl. J. Med. 2014, 370:1524-1531.