Chapter 4 : Pathogenesis and Virulence Factor Regulation

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Pathogenesis and Virulence Factor Regulation, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818524/9781555816766_Chap04-1.gif /docserver/preview/fulltext/10.1128/9781555818524/9781555816766_Chap04-2.gif


is a gram-positive bacterium that is a component of the commensal flora of the skin and the nares. is responsible for causing significant morbidity and mortality, resulting in nearly 300,000 hospitalizations and 19,000 deaths in the United States annually. Surface-associated factors enable to bind to biotic surfaces, abiotic surfaces, and itself. The ability to adhere to varied surfaces likely represents the first step during the infection process, in which the bacterium attaches and grows on different tissues. The ability of to infect many tissues in the mammalian body suggests that this bacterium is extremely efficient at adapting to different environments. In order to monitor the density of the population and prevent starvation and/or clearance by the host, most bacteria secrete small molecules into the extracellular milieu that accumulate in response to an increase in the number of bacteria in a defined space. These so-called autoinducers are sensed by the entire population, triggering a signaling cascade that informs the community that quorum has been attained. Numerous regulatory networks work with or against one another to carefully coordinate the precise expression and production of a large collection of virulence factors that play different roles in infection. A critical layer of complexity to this topic is the tremendous strain-to-strain variability seen in clinical isolates. This variability often influences the expression of virulence factors, which directly alters the pathogenic trait of clinical isolates.

Citation: Torres V, Benson M, Voyich J. 2013. Pathogenesis and Virulence Factor Regulation, p 58-78. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch4
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Microarray analysis of strains and growth conditions. Blue indicates genes which were downregulated in indicated condition or mutant, red indicates upregulated genes, and yellow indicates no change. White denotes that the gene was not included in the particular microarray analysis. Transcription profiles of strains LAC and MW2 following neutrophil (PMN) phagocytosis were performed by Malachowa et al. ( ). Transcription profiles of strains LAC and MW2 were performed by Voyich et al. ( ). Comparison of the transcription profiles between USA300 CAMRSA wild-type (WT) strain LAC and a Δ or a Δ isogenic mutant strain were performed by Cheung et al. ( ) and Nygaard et al. ( ), respectively. Experiments comparing the transcription profile of the USA400 CA-MRSA WT strain MW2 to that of a Δ or Δ or an Δ isogenic mutant strain were performed by Queck et al. ( ) and Voyich et al. ( ), respectively. doi:10.1128/9781555818524.ch4f1

Citation: Torres V, Benson M, Voyich J. 2013. Pathogenesis and Virulence Factor Regulation, p 58-78. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

regulates the production of virulence factors in a growth phase-dependent manner. Shown is a schematic representation of the association of growth in vitro (black line) and the production of surface virulence factors (green line) and cytotoxins (red line). Early in log phase, produces high levels of surface proteins and low levels of cytotoxins. In contrast, at the transition between late log and stationary phase, concomitantly downregulates the production of surface proteins and upregulates the production of cytotoxins. doi:10.1128/9781555818524.ch4f2

Citation: Torres V, Benson M, Voyich J. 2013. Pathogenesis and Virulence Factor Regulation, p 58-78. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

The Agr system. The diagram depicts the Agr quorum sensing TCS. Upon reaching quorum, the Agr TCS is activated by binding of AIP to AgrC, resulting in the autophosphorylation of AgrC. AgrC then phosphorylates ArgA, which subsequently binds and activates the P2 and P3 promoters. Activation of the P2 promoter results in the expression of the multicistronic RNAII transcript and increased production of AgrB, AgrD, AgrC, and AgrA, and thus continuous activation of the system. Activation of the P3 promoter results in the expression of RNAIII transcript, which is itself a regulatory RNA and also codes for delta-hemolysin. Production of RNAIII regulates the expression and production of virulence factors directly via RNAIII-target mRNA interactions and indirectly via RNAIII-mediated inhibition of Rot synthesis. Rot (see p. 66) represses the expression of cytotoxin-encoding genes and activates the expression of genes coding for cell surface proteins. doi:10.1128/9781555818524.ch4f3

Citation: Torres V, Benson M, Voyich J. 2013. Pathogenesis and Virulence Factor Regulation, p 58-78. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

The Agr system AIPs. Shown is a schematic representation of the four different AIP molecules (AIP I to IV). The sequences of AIP I and AIP IV differ only by a single amino acid in the thiolactone ring. doi:10.1128/9781555818524.ch4f4

Citation: Torres V, Benson M, Voyich J. 2013. Pathogenesis and Virulence Factor Regulation, p 58-78. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

Structure and mechanism of action of RNAIII. The diagrams depict the secondary structure of RNAIII (A) and the 5′ UTR sequences of (B) and (C). Binding of RNAIII to the 5′ UTR sequence results in the formation of a double-stranded RNA molecule that is recognized and degraded by RNase III. In contrast, binding of RNAIII to the 5′ UTR sequence enables translation of the mRNA. doi:10.1128/9781555818524.ch4f5

Citation: Torres V, Benson M, Voyich J. 2013. Pathogenesis and Virulence Factor Regulation, p 58-78. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6
Figure 6

The SaeRS TCS. The diagram depicts the organization of the locus and the predicted localization of the Sae components. The P3 promoter of the is constitutively active, resulting in basal level expression of and . Upon exposure to a signal (lightning bolt), SaeS is autophosphorylated, followed by phosphotransfer from SaeS to SaeR. Phosphorylation of SaeR enhances the DNA binding activity of this transcriptional regulator, resulting in binding and activation of the P1 promoter and thus autoinduction. In addition, activated SaeR binds to target promoters containing the SaeR binding sequence, resulting in their increased expression of these genes. doi:10.1128/9781555818524.ch4f6

Citation: Torres V, Benson M, Voyich J. 2013. Pathogenesis and Virulence Factor Regulation, p 58-78. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Adem, P. V.,, C. P. Montgomery,, A. N. Husain,, T. K. Koogler,, V. Arangelovich,, M. Humilier,, S. Boyle-Vavra,, and R. S. Daum. 2005. Staphylococcus aureus sepsis and the Waterhouse-Friderichsen syndrome in children. N. Engl. J. Med. 353:12451251.
2. Adhikari, R. P.,, and R. P. Novick. 2008. Regulatory organization of the staphylococcal sae locus. Microbiology 154:949959.
3. Agerer, F.,, A. Michel,, K. Ohlsen,, and C. R. Hauck. 2003. Integrin-mediated invasion of Staphylococcus aureus into human cells requires Src family protein-tyrosine kinases. J. Biol. Chem. 278:4252442531.
4. Baba, T.,, T. Bae,, O. Schneewind,, F. Takeuchi,, and K. Hiramatsu. 2008. Genome sequence of Staphylococcus aureus strain Newman and comparative analysis of staphylococcal genomes: polymorphism and evolution of two major pathogenicity islands. J. Bacteriol. 190:300310.
5. Bader, M. W.,, W. W. Navarre,, W. Shiau,, H. Nikaido,, J. G. Frye,, M. McClelland,, F. C. Fang,, and S. I. Miller. 2003. Regulation of Salmonella typhimurium virulence gene expression by cationic antimicrobial peptides. Mol. Microbiol. 50:219230.
6. Bader, M. W.,, S. Sanowar,, M. E. Daley,, A. R. Schneider,, U. Cho,, W. Xu,, R. E. Klevit,, H. Le Moual,, and S. I. Miller. 2005. Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell 122:461472.
7. Bae, T.,, A. K. Banger,, A. Wallace,, E. M. Glass,, F. Aslund,, O. Schneewind,, and D. M. Missiakas. 2004. Staphylococcus aureus virulence genes identified by bursa aurealis mutagenesis and nematode killing. Proc. Natl. Acad. Sci. USA 101:1231212317.
8. Benito, Y.,, F. A. Kolb,, P. Romby,, G. Lina,, J. Etienne,, and F. Vandenesch. 2000. Probing the structure of RNAIII, the Staphylococcus aureus agr regulatory RNA, and identification of the RNA domain involved in repression of protein A expression. RNA 6:668679.
9. Benson, M. A.,, S. Lilo,, G. A. Wasserman,, M. Thoendel,, A. Smith,, A. R. Horswill,, J. Fraser,, R. P. Novick,, B. Shopsin,, and V. J. Torres. 2011. Staphylococcus aureus regulates the expression and production of the staphylococcal superantigen-like secreted proteins in a Rot-dependent manner. Mol. Microbiol. 81:659675.
10. Benton, B. M.,, J. P. Zhang,, S. Bond,, C. Pope,, T. Christian,, L. Lee,, K. M. Winterberg,, M. B. Schmid,, and J. M. Buysse. 2004. Large-scale identification of genes required for full virulence of Staphylococcus aureus. J. Bacteriol. 186:84788489.
11. Bischoff, M.,, P. Dunman,, J. Kormanec,, D. Macapagal,, E. Murphy,, W. Mounts,, B. Berger-Bachi,, and S. Projan. 2004. Microarray-based analysis of the Staphylococcus aureus σB regulon. J. Bacteriol. 186:40854099.
12. Bodey, G. P.,, M. Buckley,, Y. S. Sathe,, and E. J. Freireich. 1966. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann. Intern. Med. 64:328340.
13. Boisset, S.,, T. Geissmann,, E. Huntzinger,, P. Fechter,, N. Bendridi,, M. Possedko,, C. Chevalier,, A. C. Helfer,, Y. Benito,, A. Jacquier,, C. Gaspin,, F. Vandenesch,, and P. Romby. 2007. Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism. Genes Dev. 21:13531366.
14. Boles, B. R.,, and A. R. Horswill. 2008. Agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog. 4:e1000052.
15. Booth, M. C.,, R. V. Atkuri,, S. K. Nanda,, J. J. Iandolo,, and M. S. Gilmore. 1995. Accessory gene regulator controls Staphylococcus aureus virulence in endophthalmitis. Investig. Ophthalmol. Vis. Sci. 36:18281836.
16. Bronner, S.,, H. Monteil,, and G. Prevost. 2004. Regulation of virulence determinants in Staphylococcus aureus: complexity and applications. FEMS Microbiol. Rev. 28:183200.
17. Brown, D. R.,, and P. A. Pattee. 1980. Identification of a chromosomal determinant of alpha-toxin production in Staphylococcus aureus. Infect. Immun. 30:3642.
18. Brown, E. L.,, O. Dumitrescu,, D. Thomas,, C. Badiou,, E. M. Koers,, P. Choudhury,, V. Vazquez,, J. Etienne,, G. Lina,, F. Vandenesch,, and M. G. Bowden. 2009. The Panton-Valentine leukocidin vaccine protects mice against lung and skin infections caused by Staphylococcus aureus USA300. Clin. Microbiol. Infect. 15:156164.
19. Bubeck Wardenburg, J.,, T. Bae,, M. Otto,, F. R. Deleo,, and O. Schneewind. 2007a. Poring over pores: alpha-hemolysin and Panton-Valentine leukocidin in Staphylococcus aureus pneumonia. Nat. Med. 13:14051406.
20. Bubeck Wardenburg, J.,, R. J. Patel,, and O. Schneewind. 2007b. Surface proteins and exotoxins are required for the pathogenesis of Staphylococcus aureus pneumonia. Infect. Immun. 75:10401044.
21. Bubeck Wardenburg, J.,, and O. Schneewind. 2008. Vaccine protection against Staphylococcus aureus pneumonia. J. Exp. Med. 205:287294.
22. Burian, M.,, M. Rautenberg,, T. Kohler,, M. Fritz,, B. Krismer,, C. Unger,, W. H. Hoffmann,, A. Peschel,, C. Wolz,, and C. Goerke. 2010a. Temporal expression of adhesion factors and activity of global regulators during establishment of Staphylococcus aureus nasal colonization. J. Infect. Dis. 201:14141421.
23. Burian, M.,, C. Wolz,, and C. Goerke. 2010b. Regulatory adaptation of Staphylococcus aureus during nasal colonization of humans. PLoS One 5:e10040.
24. Burlak, C.,, C. H. Hammer,, M. A. Robinson,, A. R. Whitney,, M. J. McGavin,, B. N. Kreiswirth,, and F. R. Deleo. 2007. Global analysis of community-associated methicillin-resistant Staphylococcus aureus exoproteins reveals molecules produced in vitro and during infection. Cell. Microbiol. 9:11721190.
25. Cassat, J.,, P. M. Dunman,, E. Murphy,, S. J. Projan,, K. E. Beenken,, K.J. Palm,, S. J. Yang,, K. C. Rice,, K. W. Bayles,, and M. S. Smeltzer. 2006. Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390. Microbiology 152:30753090.
26. Centers for Disease Control and Prevention. 1999. Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus—Minnesota and North Dakota, 1997–1999. JAMA 282:11231125.
27. Centers for Disease Control and Prevention. 2002a. Staphylococcus aureus resistant to vancomycin—United States, 2002. MMWR Morb. Mortal. Wkly. Rep. 51:565567.
28. Centers for Disease Control and Prevention. 2002b. Vancomycin-resistant Staphylococcus aureus—Pennsylvania, 2002. MMWR Morb. Mortal. Wkly. Rep. 51:902.
29. Centers for Disease Control and Prevention. 2004. Vancomycin-resistant Staphylococcus aureus—New York, 2004. MMWR Morb. Mortal. Wkly. Rep. 53:322323.
30. Cheng, A. G.,, M. McAdow,, H. K. Kim,, T. Bae,, D. M. Missiakas,, and O. Schneewind. 2010. Contribution of coagulases towards Staphylococcus aureus disease and protective immunity. PLoS Pathog. 6:e1001036.
31. Cheung, A. L.,, A. S. Bayer,, G. Zhang,, H. Gresham,, and Y. Q. Xiong. 2004. Regulation of virulence determinants in vitro and in vivo in Staphylococcus aureus. FEMS Immunol. Med. Microbiol. 40:19.
32. Cheung, A. L.,, K. J. Eberhardt,, E. Chung,, M. R. Yeaman,, P. M. Sullam,, M. Ramos,, and A. S. Bayer. 1994. Diminished virulence of a sar-/agr- mutant of Staphylococcus aureus in the rabbit model of endocarditis. J. Clin. Investig. 94:18151822.
33. Cheung, A. L.,, J. M. Koomey,, C. A. Butler,, S. J. Projan,, and V.A. Fischetti. 1992. Regulation of exoprotein expression in Staphylococcus aureus by a locus (sar) distinct from agr. Proc. Natl. Acad. Sci. USA 89:64626466.
34. Cheung, G. Y.,, R. Wang,, B. A. Khan,, D. E. Sturdevant,, and M. Otto. 2011. Role of the accessory gene regulator agr in community-associated methicillin-resistant Staphylococcus aureus pathogenesis. Infect. Immun. 79:19271935.
35. Corrigan, R. M.,, H. Miajlovic,, and T. J. Foster. 2009. Surface proteins that promote adherence of Staphylococcus aureus to human desquamated nasal epithelial cells. BMC Microbiol. 9:22.
36. Cronstein, B. N. 1994. Adenosine, an endogenous anti-inflammatory agent. J. Appl. Physiol. 76:513.
37. Dale, D. C.,, D. T. Guerry,, J. R. Wewerka,, J. M. Bull,, and M. J. Chusid. 1979. Chronic neutropenia. Medicine (Baltimore) 58:128144.
38. Deleo, F. R.,, M. Otto,, B. N. Kreiswirth,, and H. F. Chambers. 2010. Community-associated methicillin-resistant Staphylococcus aureus. Lancet 375:15571568.
39. Diep, B. A.,, L. Chan,, P. Tattevin,, O. Kajikawa,, T. R. Martin,, L. Basuino,, T. T. Mai,, H. Marbach,, K. R. Braughton,, A. R. Whitney,, D. J. Gardner,, X. Fan,, C. W. Tseng,, G. Y. Liu,, C. Badiou,, J. Etienne,, G. Lina,, M. A. Matthay,, F. R. DeLeo,, and H. F. Chambers. 2010.Polymorphonuclear leukocytes mediate Staphylococcus aureus Panton-Valentine leukocidin-induced lung inflammation and injury. Proc. Natl. Acad. Sci. USA 107:55875592.
40. Dufour, P.,, S. Jarraud,, F. Vandenesch,, T. Greenland,, R. P. Novick,, M. Bes,, J. Etienne,, and G. Lina. 2002. High genetic variability of the agr locus in Staphylococcus species. J. Bacteriol. 184:11801186.
41. Dumont, A. L.,, T. K. Nygaard,, R. L. Watkins,, A. Smith,, L. Kozhaya,, B. N. Kreiswirth,, B. Shopsin,, D. Unutmaz,, J. M. Voyich,, and V. J. Torres. 2011. Characterization of a new cytotoxin that contributes to Staphylococcus aureus pathogenesis. Mol. Microbiol. 79:814825.
42. Dunman, P. M.,, E. Murphy,, S. Haney,, D. Palacios,, G. Tucker-Kellogg,, S. Wu,, E. L. Brown,, R. J. Zagursky,, D. Shlaes,, and S. J. Projan. 2001. Transcription profiling-based identification of Staphylococcus aureus genes regulated by the agr and/or sarA loci. J. Bacteriol. 183:73417353.
43. Duthie, E. S.,, and L. L. Lorenz. 1952. Staphylococcal coagulase; mode of action and antigenicity. J. Gen. Microbiol. 6:95107.
44. Felden, B.,, F. Vandenesch,, P. Bouloc,, and P. Romby. 2011. The Staphylococcus aureus RNome and its commitment to virulence. PLoS Pathog. 7:e1002006.
45. Fleming, V.,, E. Feil,, A. K. Sewell,, N. Day,, A. Buckling,, and R. C. Massey. 2006. Agr interference between clinical Staphylococcus aureus strains in an insect model of virulence. J. Bacteriol. 188:76867688.
46. Foster, T. J. 2005. Immune evasion by staphylococci. Nat. Rev. Microbiol. 3:948958.
47. Fowler, V. G., Jr.,, G. Sakoulas,, L. M. McIntyre,, V. G. Meka,, R. D. Arbeit,, C. H. Cabell,, M. E. Stryjewski,, G. M. Eliopoulos,, L. B. Reller,, G. R. Corey,, T. Jones,, N. Lucindo,, M. R. Yeaman,, and A. S. Bayer. 2004. 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. 190:11401149.
48. Fraser, J. D.,, and T. Proft. 2008. The bacterial superantigen and superantigen-like proteins. Immunol. Rev. 225:226243.
49. Fridkin, S. K.,, J. C. Hageman,, M. Morrison,, L. T. Sanza,, K. Como-Sabetti,, J. A. Jernigan,, K. Harriman,, L. H. Harrison,, R. Lynfield,, and M. M. Farley. 2005. Methicillin-resistant Staphylococcus aureus disease in three communities. N. Engl. J. Med. 352:14361444.
50. Geiger, T.,, C. Goerke,, M. Mainiero,, D. Kraus,, and C. Wolz. 2008. The virulence regulator Sae of Staphylococcus aureus: promoter activities and response to phagocytosis-related signals. J. Bacteriol. 190:34193428.
51. Geisinger, E.,, R. P. Adhikari,, R. Jin,, H. F. Ross,, and R. P. Novick. 2006. Inhibition of rot translation by RNAIII, a key feature of agr function. Mol. Microbiol. 61:10381048.
52. Gillaspy, A. F.,, S. G. Hickmon,, R. A. Skinner,, J. R. Thomas,, C. L. Nelson,, and M. S. Smeltzer. 1995. Role of the accessory gene regulator (agr) in pathogenesis of staphylococcal osteomyelitis. Infect. Immun. 63:33733380.
53. Gillet, Y.,, B. Issartel,, P. Vanhems,, J. C. Fournet,, G. Lina,, M. Bes,, F. Vandenesch,, Y. Piemont,, N. Brousse,, D. Floret,, and J. Etienne. 2002. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 359:753759.
54. Giraudo, A. T.,, A. Calzolari,, A. A. Cataldi,, C. Bogni,, and R. Nagel. 1999. The sae locus of Staphylococcus aureus encodes a two-component regulatory system. FEMS Microbiol. Lett. 177:1522.
55. Giraudo, A. T.,, A. L. Cheung,, and R. Nagel. 1997. The sae locus of Staphylococcus aureus controls exoprotein synthesis at the transcriptional level. Arch. Microbiol. 168:5358.
56. Giraudo, A. T.,, H. Rampone,, A. Calzolari,, and R. Nagel. 1996. Phenotypic characterization and virulence of a sae- agr- mutant of Staphylococcus aureus. Can. J. Microbiol. 42:120123.
57. Giraudo, A. T.,, C. G. Raspanti,, A. Calzolari,, and R. Nagel. 1994. Characterization of a Tn551-mutant of Staphylococcus aureus defective in the production of several exoproteins. Can. J. Microbiol. 40:677681.
58. Goerke, C.,, U. Fluckiger,, A. Steinhuber,, W. Zimmerli,, and C. Wolz. 2001. Impact of the regulatory loci agr, sarA and sae of Staphylococcus aureus on the induction of alpha-toxin during device-related infection resolved by direct quantitative transcript analysis. Mol. Microbiol. 40:14391447.
59. Gomez, M. I.,, M. O’Seaghdha,, M. Magargee,, T. J. Foster,, and A. S. Prince. 2006. Staphylococcus aureus protein A activates TNFR1 signaling through conserved IgG binding domains. J. Biol. Chem. 281:2019020196.
60. Gomez, M. I.,, M. O. Seaghdha,, and A. S. Prince. 2007. Staphylococcus aureus protein A activates TACE through EGFR-dependent signaling. EMBO J. 26:701709.
61. Harraghy, N.,, J. Kormanec,, C. Wolz,, D. Homerova,, C. Goerke,, K. Ohlsen,, S. Qazi,, P. Hill,, and M. Herrmann. 2005. sae is essential for expression of the staphylococcal adhesins Eap and Emp. Microbiology 151:17891800.
62. Hecker, M.,, J. Pane-Farre,, and U. Volker. 2007. SigB-dependent general stress response in Bacillus subtilis and related gram-positive bacteria. Annu. Rev. Microbiol. 61:215236.
63. Heilmann, C. 2011. Adhesion mechanisms of staphylococci. Adv. Exp. Med. Biol. 715:105123.
64. Hirschhausen, N.,, T. Schlesier,, M. A. Schmidt,, F. Gotz,, G. Peters,, and C. Heilmann. 2010. A novel staphylococcal internalization mechanism involves the major autolysin Atl and heat shock cognate protein Hsc70 as host cell receptor. Cell. Microbiol. 12:17461764.
65. Hoch, J. A. 2000. Two-component and phosphorelay signal transduction. Curr. Opin. Microbiol. 3:165170.
66. Horsburgh, M. J.,, J. L. Aish,, I. J. White,, L. Shaw,, J. K. Lithgow,, and S. J. Foster. 2002. σBmodulates virulence determinant expression and stress resistance: characterization of a functional rsbU strain derived from Staphylococcus aureus8325-4. J. Bacteriol. 184:54575467.
67. Huntzinger, E.,, S. Boisset,, C. Saveanu,, Y. Benito,, T. Geissmann,, A. Namane,, G. Lina,, J. Etienne,, B. Ehresmann,, C. Ehresmann,, A. Jacquier,, F. Vandenesch,, and P. Romby. 2005. Staphylococcus aureus RNAIII and the endoribonuclease III coordinately regulate spa gene expression. EMBO J. 24:824835.
68. Janzon, L.,, S. Lofdahl,, and S. Arvidson. 1989. Identification and nucleotide sequence of the delta-lysin gene, hld, adjacent to the accessory gene regulator (agr) of Staphylococcus aureus. Mol. Gen. Genet. 219:480485.
69. Jarraud, S.,, C. Mougel,, J. Thioulouse,, G. Lina,, H. Meugnier,, F. Forey,, X. Nesme,, J. Etienne,, and F. Vandenesch. 2002. Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease. Infect. Immun. 70:631641.
70. Jevons, M. P.,, and M. T. Parker. 1964. The evolution of new hospital strains of Staphylococcus aureus. J. Clin. Pathol. 17:243250.
71. Ji, G.,, R. Beavis,, and R. P. Novick. 1997. Bacterial interference caused by autoinducing peptide variants. Science 276:20272030.
72. Ji, G.,, R. C. Beavis,, and R. P. Novick. 1995. Cell density control of staphylococcal virulence mediated by an octapeptide pheromone. Proc. Natl. Acad. Sci. USA 92:1205512059.
73. Joo, H. S.,, J. L. Chan,, G. Y. Cheung,, and M. Otto. 2010. Subinhibitory concentrations of protein synthesis-inhibiting antibiotics promote increased expression of the agr virulence regulator and production of phenol-soluble modulin cytolysins in community-associated methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 54:49424944.
74. Katayama, Y.,, T. Ito,, and K. Hiramatsu. 2000. A new class of genetic element, staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 44:15491555.
75. Kavanaugh, J. S.,, M. Thoendel,, and A. R. Horswill. 2007. A role for type I signal peptidase in Staphylococcus aureus quorum sensing. Mol. Microbiol. 65:780798.
76. Kazakova, S. V.,, J. C. Hageman,, M. Matava,, A. Srinivasan,, L. Phelan,, B. Garfinkel,, T. Boo,, S. McAllister,, J. Anderson,, B. Jensen,, D. Dodson,, D. Lonsway,, L. K. McDougal,, M. Arduino,, V. J. Fraser,, G. Killgore,, F. C. Tenover,, S. Cody,, and D. B. Jernigan. 2005. A clone of methicillin-resistant Staphylococcus aureus among professional football players. N. Engl. J. Med. 352:468475.
77. Kennedy, A. D.,, J. Bubeck Wardenburg,, D. J. Gardner,, D. Long,, A.R. Whitney,, K. R. Braughton,, O. Schneewind,, and F. R. DeLeo. 2010. Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. J. Infect. Dis. 202:10501058.
78. Kielian, T.,, A. Cheung,, and W. F. Hickey. 2001. Diminished virulence of an alpha-toxin mutant of Staphylococcus aureus in experimental brain abscesses. Infect. Immun. 69:69026911.
79. Kim, H. K.,, A. G. Cheng,, H. Y. Kim,, D. M. Missiakas,, and O. Schneewind. 2010. Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice. J. Exp. Med. 207:18631870.
80. Kintarak, S.,, S. A. Whawell,, P. M. Speight,, S. Packer,, and S. P. Nair. 2004. Internalization of Staphylococcus aureus by human keratinocytes. Infect. Immun. 72:56685675.
81. Klevens, R. M.,, M. A. Morrison,, J. Nadle,, S. Petit,, K. Gershman,, S. Ray,, L. H. Harrison,, R. Lynfield,, G. Dumyati,, J. M. Townes,, A. S. Craig,, E. R. Zell,, G. E. Fosheim,, L. K. McDougal,, R. B. Carey,, and S. K. Fridkin. 2007. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298:17631771.
82. Kobayashi, S. D.,, J. M. Voyich,, K. R. Braughton,, and F. R. DeLeo. 2003a. Down-regulation of proinflammatory capacity during apoptosis in human polymorphonuclear leukocytes. J. Immunol. 170:33573368.
83. Kobayashi, S. D.,, J. M. Voyich,, and F. R. DeLeo. 2003b. Regulation of the neutrophil-mediated inflammatory response to infection. Microbes Infect. 5:13371344.
84. Kobayashi, S. D.,, J. M. Voyich,, G. A. Somerville,, K. R. Braughton,, H. L. Malech,, J. M. Musser,, and F. R. DeLeo. 2003c. An apoptosis-differentiation program in human polymorphonuclear leukocytes facilitates resolution of inflammation. J. Leukoc. Biol. 73:315322.
85. Koenig, R. L.,, J. L. Ray,, S. J. Maleki,, M. S. Smeltzer,, and B. K. Hurlburt. 2004. Staphylococcus aureus AgrA binding to the RNAIII-agr regulatory region. J. Bacteriol. 186:75497555.
86. Kravitz, G. R.,, D. J. Dries,, M. L. Peterson,, and P. M. Schlievert. 2005. Purpura fulminans due to Staphylococcus aureus. Clin. Infect. Dis. 40:941947.
87. Kuehnert, M. J.,, D. Kruszon-Moran,, H. A. Hill,, G. McQuillan,, S. K. McAllister,, G. Fosheim,, L. K. McDougal,, J. Chaitram,, B. Jensen,, S. K. Fridkin,, G. Killgore,, and F. C. Tenover. 2006. Prevalence of Staphylococcus aureus nasal colonization in the United States, 2001-2002. J. Infect. Dis. 193:172179.
88. Kuroda, H.,, M. Kuroda,, L. Cui,, and K. Hiramatsu. 2007. Subinhibitory concentrations of beta-lactam induce haemolytic activity in Staphylococcus aureus through the SaeRS two-component system. FEMS Microbiol. Lett. 268:98105.
89. Kuroda, M.,, H. Kuroda,, T. Oshima,, F. Takeuchi,, H. Mori,, and K. Hiramatsu. 2003. Two-component system VraSR positively modulates the regulation of cell-wall biosynthesis pathway in Staphylococcus aureus. Mol. Microbiol. 49:807821.
90. Lauderdale, K. J.,, B. R. Boles,, A. L. Cheung,, and A. R. Horswill. 2009. Interconnections between sigma B, agr, and proteolytic activity in Staphylococcus aureus biofilm maturation. Infect. Immun. 77:16231635.
91. Laurell, G.,, and G. Wallmark. 1953. Studies on Staphylococcus aureus pyogenes in a children’s hospital. III. Results of phage-typing and tests for penicillin resistance of 2,474 strains isolated from patients and staff. Acta Pathol. Microbiol. Scand. 32:438447.
92. Lekstrom-Himes, J. A.,, and J. I. Gallin. 2000. Immunodeficiency diseases caused by defects in phagocytes. N. Engl. J. Med. 343:17031714.
93. Li, M.,, B. A. Diep,, A. E. Villaruz,, K. R. Braughton,, X. Jiang,, F. R. DeLeo,, H. F. Chambers,, Y. Lu,, and M. Otto. 2009. Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus. Proc. Natl. Acad. Sci. USA 106:58835888.
94. Li, M.,, Y. Lai,, A. E. Villaruz,, D. J. Cha,, D. E. Sturdevant,, and M. Otto. 2007. Gram-positive three-component antimicrobial peptide-sensing system. Proc. Natl. Acad. Sci. USA 104:94699474.
95. Liang, X.,, C. Yu,, J. Sun,, H. Liu,, C. Landwehr,, D. Holmes,, and Y. Ji. 2006. Inactivation of a two-component signal transduction system, SaeRS, eliminates adherence and attenuates virulence of Staphylococcus aureus. Infect. Immun. 74:46554665.
96. Lina, G.,, S. Jarraud,, G. Ji,, T. Greenland,, A. Pedraza,, J. Etienne,, R. P. Novick,, and F. Vandenesch. 1998. Transmembrane topology and histidine protein kinase activity of AgrC, the agr signal receptor in Staphylococcus aureus. Mol. Microbiol. 28:655662.
97. Lindmark, R.,, K. Thoren-Tolling,, and J. Sjoquist. 1983 Binding of immunoglobulins to protein A and immunoglobulin levels in mammalian sera. J. Immunol. Methods 62:113.
98. Lowy, F. D. 1998. Staphylococcus aureus infections. N. Engl. J. Med. 339:520532.
99. Lowy, F. D. 2003. Antimicrobial resistance: the example of Staphylococcus aureus. J. Clin. Investig. 111:12651273.
100. Lowy, F. D. 2007. Secrets of a superbug. Nat. Med. 13:14181420.
101. Mainiero, M.,, C. Goerke,, T. Geiger,, C. Gonser,, S. Herbert,, and C. Wolz. 2010. Differential target gene activation by the Staphylococcus aureus two-component system saeRS. J. Bacteriol. 192:613623.
102. Malachowa, N.,, A. R. Whitney,, S. D. Kobayashi,, D. E. Sturdevant,, A. D. Kennedy,, K. R. Braughton,, D. W. Shabb,, B. A. Diep,, H. F. Chambers,, M. Otto,, and F. R. Deleo. 2011. Global changes in Staphylococcus aureus gene expression in human blood. PLoS One 6:e18617.
103. Mann, E. E.,, K. C. Rice,, B. R. Boles,, J. L. Endres,, D. Ranjit,, L. Chandramohan,, L. H. Tsang,, M. S. Smeltzer,, A. R. Horswill,, and K. W. Bayles. 2009. Modulation of eDNA release and degradation affects Staphylococcus aureus biofilm maturation. PLoS One 4:e5822.
104. Martin, F. J.,, M. I. Gomez,, D. M. Wetzel,, G. Memmi,, M. O’Seaghdha,, G. Soong,, C. Schindler,, and A. Prince. 2009. Staphylococcus aureus activates type I IFN signaling in mice and humans through the Xr repeated sequences of protein A. J. Clin. Investig. 119:19311939.
105. McNamara, P. J.,, and A. S. Bayer. 2005. A rot mutation restores parental virulence to an agr-null Staphylococcus aureus strain in a rabbit model of endocarditis. Infect. Immun. 73:38063809.
106. McNamara, P. J.,, K. C. Milligan-Monroe,, S. Khalili,, and R. A. Proctor. 2000. Identification, cloning, and initial characterization of rot, a locus encoding a regulator of virulence factor expression in Staphylococcus aureus. J. Bacteriol. 182:31973203.
107. Menestrina, G.,, M. Dalla Serra,, M. Comai,, M. Coraiola,, G. Viero,, S. Werner,, D. A. Colin,, H. Monteil,, and G. Prevost. 2003. Ion channels and bacterial infection: the case of beta-barrel pore-forming protein toxins of Staphylococcus aureus. FEBS Lett. 552:5460.
108. Menzies, B. E.,, and D. S. Kernodle. 1996. Passive immunization with antiserum to a nontoxic alpha-toxin mutant from Staphylococcus aureus is protective in a murine model. Infect. Immun. 64:18391841.
109. Miller, L. G.,, F. Perdreau-Remington,, G. Rieg,, S. Mehdi,, J. Perlroth,, A. S. Bayer,, A. W. Tang,, T. O. Phung,, and B. Spellberg. 2005. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N. Engl. J. Med. 352:14451453.
110. Montgomery, C. P.,, S. Boyle-Vavra,, P. V. Adem,, J. C. Lee,, A. N. Husain,, J. Clasen,, and R. S. Daum. 2008. Comparison of virulence in community-associated methicillin-resistantStaphylococcus aureus pulsotypes USA300 and USA400 in a rat model of pneumonia. J. Infect. Dis. 198:561570.
111. Montgomery, C. P.,, S. Boyle-Vavra,, and R. S. Daum. 2010. Importance of the global regulators Agr and SaeRS in the pathogenesis of CA-MRSA USA300 infection. PLoS One 5:e15177.
112. Moran, G. J.,, A. Krishnadasan,, R. J. Gorwitz,, G. E. Fosheim,, L. K. McDougal,, R. B. Carey,, and D. A. Talan. 2006. Methicillin-resistant S. aureus infections among patients in the emergency department. N. Engl. J. Med. 355:666674.
113. Morfeldt, E.,, D. Taylor,, A. von Gabain,, and S. Arvidson. 1995. Activation of alpha-toxin translation in Staphylococcus aureus by the trans-encoded antisense RNA, RNAIII. EMBO J. 14:45694577.
114. Morfeldt, E.,, K. Tegmark,, and S. Arvidson. 1996. Transcriptional control of the agr-dependent virulence gene regulator, RNAIII, in Staphylococcus aureus. Mol. Microbiol. 21:12271237.
115. Nemeth, Z. H.,, B. Csoka,, J. Wilmanski,, D. Xu,, Q. Lu,, C. Ledent,, E. A. Deitch,, P. Pacher,, Z. Spolarics,, and G. Hasko. 2006. Adenosine A2A receptor inactivation increases survival in polymicrobial sepsis. J. Immunol. 176:56165626.
116. Nizet, V. 2007. Understanding how leading bacterial pathogens subvert innate immunity to reveal novel therapeutic targets. J. Allergy Clin. Immunol. 120:1322.
117. Novick, R. P. 1991. Genetic systems in staphylococci. Methods Enzymol. 204:587636.
118. Novick, R. P. 2003. Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol. Microbiol. 48:14291449.
119. Novick, R. P.,, and E. Geisinger. 2008. Quorum sensing in staphylococci. Annu. Rev. Genet. 42:541–564.
120. Novick, R. P.,, and D. Jiang. 2003. The staphylococcal saeRS system coordinates environmental signals with agr quorum sensing. Microbiology 149:27092717.
121. Novick, R. P.,, S. Projan,, J. Kornblum,, H. Ross,, B. Kreiswirth,, and S. Moghazeh. 1995. The agr P-2 operon: an autocatalytic sensory transduction system in Staphylococcus aureus. Mol. Gen. Genet. 248:446458.
122. Novick, R. P.,, H. F. Ross,, S. J. Projan,, J. Kornblum,, B. Kreiswirth,, and S. Moghazeh. 1993. Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J. 12:39673975.
123. Nygaard, T. K.,, F. R. DeLeo,, and J. M. Voyich. 2008. Community-associated methicillin-resistant Staphylococcus aureus skin infections: advances toward identifying the key virulence factors. Curr. Opin. Infect. Dis. 21:147152.
124. Nygaard, T. K.,, K. B. Pallister,, P. Ruzevich,, S. Griffith,, C. Vuong,, and J. M. Voyich. 2010. SaeR binds a consensus sequence within virulence gene promoters to advance USA300 pathogenesis. J. Infect. Dis. 201:241254.
125. Oviedo-Boyso, J.,, R. Cortes-Vieyra,, A. Huante-Mendoza,, H. B. Yu,, J. J. Valdez-Alarcon,, A. Bravo-Patino,, M. Cajero-Juarez,, B. B. Finlay,, and V. M. Baizabal-Aguirre. 2011. The PI3K-Akt signaling pathway is important for Staphylococcus aureus internalization by endothelial cells. Infect. Immun. 79:45694577.
126. Palazzolo-Ballance, A. M.,, M. L. Reniere,, K. R. Braughton,, D. E. Sturdevant,, M. Otto,, B. N. Kreiswirth,, E. P. Skaar,, and F. R. DeLeo. 2008. Neutrophil microbicides induce a pathogen survival response in community-associated methicillin-resistant Staphylococcus aureus. J. Immunol. 180:500509.
127. Pantrangi, M.,, V. K. Singh,, C. Wolz,, and S. K. Shukla. 2010. Staphylococcal superantigen-like genes, ssl5 and ssl8, are positively regulated by Sae and negatively by Agr in the Newman strain. FEMS Microbiol. Lett. 308:175184.
128. Park, J.,, R. Jagasia,, G. F. Kaufmann,, J. C. Mathison,, D. I. Ruiz,, J. A. Moss,, M. M. Meijler,, R. J. Ulevitch,, and K. D. Janda. 2007. Infection control by antibody disruption of bacterial quorum sensing signaling. Chem. Biol. 14:11191127.
129. Peterson, M. M.,, J. L. Mack,, P. R. Hall,, A. A. Alsup,, S. M. Alexander,, E. K. Sully,, Y. S. Sawires,, A. L. Cheung,, M. Otto,, and H. D. Gresham. 2008. Apolipoprotein B is an innate barrier against invasive Staphylococcus aureus infection. Cell Host Microbe 4:555566.
130. Peterson, P. K.,, J. Verhoef,, L. D. Sabath,, and P. G. Quie. 1977. Effect of protein A on staphylococcal opsonization. Infect. Immun. 15:760764.
131. Pincus, S. H.,, L. A. Boxer,, and T. P. Stossel. 1976. Chronic neutropenia in childhood. Analysis of 16 cases and a review of the literature. Am. J. Med. 61:849861.
132. Pynnonen, M.,, R. E. Stephenson,, K. Schwartz,, M. Hernandez,, and B. R. Boles. 2011. Hemoglobin promotes Staphylococcus aureus nasal colonization. PLoS Pathog. 7:e1002104.
133. Queck, S. Y.,, M. Jameson-Lee,, A. E. Villaruz,, T. H. Bach,, B. A. Khan,, D. E. Sturdevant,, S. M. Ricklefs,, M. Li,, and M. Otto. 2008. RNAIII-independent target gene control by the agr quorum-sensing system: insight into the evolution of virulence regulation in Staphylococcus aureus. Mol. Cell 32:150158.
134. Ragle, B. E.,, and J. Bubeck Wardenburg. 2009. Anti-alpha-hemolysin monoclonal antibodies mediate protection against Staphylococcus aureus pneumonia. Infect. Immun. 77:27122718.
135. Recsei, P.,, B. Kreiswirth,, M. O’Reilly,, P. Schlievert,, A. Gruss,, and R. P. Novick. 1986. Regulation of exoprotein gene expression in Staphylococcus aureus by agr. Mol. Gen. Genet. 202:5861.
136. Reyes, D.,, D. O. Andrey,, A. Monod,, W. L. Kelley,, G. Zhang,, and A. L. Cheung. 2011. Coordinated regulation by AgrA, SarA, and SarR to control agr expression in Staphylococcus aureus. J. Bacteriol. 193:60206031.
137. Reynolds, J.,, and S. Wigneshweraraj. 2011. Molecular insights into the control of transcription initiation at the Staphylococcus aureus agr operon. J. Mol. Biol. 412:862881.
138. Rice, K. C.,, E. E. Mann,, J. L. Endres,, E. C. Weiss,, J. E. Cassat,, M. S. Smeltzer,, and K. W. Bayles. 2007. The cidA murein hydrolase regulator contributes to DNA release and biofilm development in Staphylococcus aureus. Proc. Natl. Acad. Sci. USA 104:81138118.
139. Rodrigue, A.,, Y. Quentin,, A. Lazdunski,, V. Mejean,, and M. Foglino. 2000. Two-component systems in Pseudomonas aeruginosa: why so many? Trends Microbiol. 8:498504.
140. Rogasch, K.,, V. Ruhmling,, J. Pane-Farre,, D. Hoper,, C. Weinberg,, S. Fuchs,, M. Schmudde,, B. M. Broker,, C. Wolz,, M. Hecker,, and S. Engelmann. 2006. Influence of the two-component system SaeRS on global gene expression in two different Staphylococcus aureus strains. J. Bacteriol. 188:77427758.
141. Rooijakkers, S. H.,, K. P. van Kessel,, and J. A. van Strijp. 2005. Staphylococcal innate immune evasion. Trends Microbiol. 13:596601.
142. Rothfork, J. M.,, G. S. Timmins,, M. N. Harris,, X. Chen,, A. J. Lusis,, M. Otto,, A. L. Cheung,, and H. D. Gresham. 2004. Inactivation of a bacterial virulence pheromone by phagocyte-derived oxidants: new role for the NADPH oxidase in host defense. Proc. Natl. Acad. Sci. USA 101:1386713872.
143. Said-Salim, B.,, P. M. Dunman,, F. M. McAleese,, D. Macapagal,, E. Murphy,, P. J. McNamara,, S. Arvidson,, T. J. Foster,, S. J. Projan,, and B. N. Kreiswirth. 2003. Global regulation of Staphylococcus aureus genes by Rot. J. Bacteriol. 185:610619.
144. Saravolatz, L. D.,, D. J. Pohlod,, and L. M. Arking. 1982. Community-acquired methicillin-resistant Staphylococcus aureus infections: a new source for nosocomial outbreaks. Ann. Intern. Med. 97:325329.
145. Sasso, E. H.,, G. J. Silverman,, and M. Mannik. 1989. Human IgM molecules that bind staphylococcal protein A contain VHIII H chains. J. Immunol. 142:27782783.
146. Schafer, D.,, T. T. Lam,, T. Geiger,, M. Mainiero,, S. Engelmann,, M. Hussain,, A. Bosserhoff,, M. Frosch,, M. Bischoff,, C. Wolz,, J. Reidl,, and B. Sinha. 2009. A point mutation in the sensor histidine kinase SaeS of Staphylococcus aureus strain Newman alters the response to biocide exposure. J. Bacteriol. 191:73067314.
147. Schlievert, P. M.,, L. C. Case,, K. A. Nemeth,, C. C. Davis,, Y. Sun,, W. Qin,, F. Wang,, A. J. Brosnahan,, J. A. Mleziva,, M. L. Peterson,, and B. E. Jones. 2007. Alpha and beta chains of hemoglobin inhibit production of Staphylococcus aureus exotoxins. Biochemistry 46:1434914358.
148. Schweizer, M. L.,, J. P. Furuno,, G. Sakoulas,, J. K. Johnson,, A. D. Harris,, M. D. Shardell,, J. C. McGregor,, K. A. Thom,, and E. N. Perencevich. 2011. Increased mortality with accessory gene regulator (agr) dysfunction in Staphylococcus aureus among bacteremic patients. Antimicrob. Agents Chemother. 55:10821087.
149. Shopsin, B.,, A. Drlica-Wagner,, B. Mathema,, R. P. Adhikari,, B. N. Kreiswirth,, and R. P. Novick. 2008. Prevalence of agr dysfunction among colonizing Staphylococcus aureus strains. J. Infect. Dis. 198:11711174.
150. Shopsin, B.,, C. Eaton,, G. A. Wasserman,, B. Mathema,, R. P. Adhikari,, S. Agolory,, D. R. Altman,, R. S. Holzman,, B. N. Kreiswirth,, and R. P. Novick. 2010. Mutations in agr do not persist in natural populations of methicillin-resistant Staphylococcus aureus. J. Infect. Dis. 202:15931599.
151. Sifri, C. D.,, J. Park,, G. A. Helm,, M. E. Stemper,, and S. K. Shukla. 2007. Fatal brain abscess due to community-associated methicillin-resistant Staphylococcus aureus strain USA300. Clin. Infect. Dis. 45:e113e117.
152. Sinha, B.,, P. P. Francois,, O. Nusse,, M. Foti,, O. M. Hartford,, P. Vaudaux,, T. J. Foster,, D. P. Lew,, M. Herrmann,, and K. H. Krause. 1999. Fibronectin-binding protein acts as Staphylococcus aureus invasin via fibronectin bridging to integrin alpha5beta1. Cell. Microbiol. 1:101117.
153. Soong, G.,, F. J. Martin,, J. Chun,, T. S. Cohen,, D. S. Ahn,, and A. Prince. 2011. Staphylococcus aureus protein A mediates invasion across airway epithelial cells through activation of RhoA signaling and proteolytic activity. J. Biol. Chem. 286:3589135898.
154. Steinhuber, A.,, C. Goerke,, M. G. Bayer,, G. Doring,, and C. Wolz. 2003. Molecular architecture of the regulatory locus sae of Staphylococcus aureus and its impact on expression of virulence factors. J. Bacteriol. 185:62786286.
155. Sun, F.,, C. Li,, D. Jeong,, C. Sohn,, C. He,, and T. Bae. 2010. In the Staphylococcus aureus two-component system sae, the response regulator SaeR binds to a direct repeat sequence and DNA binding requires phosphorylation by the sensor kinase SaeS. J. Bacteriol. 192:21112127.
156. Thammavongsa, V.,, J. W. Kern,, D. M. Missiakas,, and O. Schneewind. 2009. Staphylococcus aureus synthesizes adenosine to escape host immune responses. J. Exp. Med. 206:24172427.
157. Thoendel, M.,, and A. R. Horswill. 2009. Identification of Staphylococcus aureus AgrD residues required for autoinducing peptide biosynthesis. J. Biol. Chem. 284:2182821838.
158. Torres, V. J.,, A. S. Attia,, W. J. Mason,, M. I. Hood,, B. D. Corbin,, F. C. Beasley,, K. L. Anderson,, D. L. Stauff,, W. H. McDonald,, L. J. Zimmerman,, D. B. Friedman,, D. E. Heinrichs,, P. M. Dunman,, and E. P. Skaar. 2010. Staphylococcus aureus fur regulates the expression of virulence factors that contribute to the pathogenesis of pneumonia. Infect. Immun. 78:16181628.
159. Traber, K. E.,, E. Lee,, S. Benson,, R. Corrigan,, M. Cantera,, B. Shopsin,, and R. P. Novick. 2008. agr function in clinical Staphylococcus aureus isolates. Microbiology 154:22652274.
160. Ventura, C. L.,, N. Malachowa,, C. H. Hammer,, G. A. Nardone,, M. A. Robinson,, S. D. Kobayashi,, and F. R. DeLeo. 2010. Identification of a novel Staphylococcus aureus two-component leukotoxin using cell surface proteomics. PLoS One 5:e11634.
161. Voyich, J. M.,, K. R. Braughton,, D. E. Sturdevant,, C. Vuong,, S.D. Kobayashi,, S. F. Porcella,, M. Otto,, J. M. Musser,, and F. R. DeLeo. 2004. Engagement of the pathogen survival response used by group A Streptococcus to avert destruction by innate host defense. J. Immunol. 173:11941201.
162. Voyich, J. M.,, K. R. Braughton,, D. E. Sturdevant,, A. R. Whitney,, B. Said-Salim,, S. F. Porcella,, R. D. Long,, D. W. Dorward,, D. J. Gardner,, B. N. Kreiswirth,, J. M. Musser,, and F. R. Deleo. 2005. Insights into mechanisms used by Staphylococcus aureus to avoid destruction by human neutrophils. J. Immunol. 175:39073919.
163. Voyich, J. M.,, M. Otto,, B. Mathema,, K. R. Braughton,, A. R. Whitney,, D. Welty,, R. D. Long,, D. W. Dorward,, D. J. Gardner,, G. Lina,, B. N. Kreiswirth,, and F. R. DeLeo. 2006. Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease? J. Infect. Dis. 194:17611770.
164. Voyich, J. M.,, C. Vuong,, M. DeWald,, T. K. Nygaard,, S. Kocianova,, S. Griffith,, J. Jones,, C. Iverson,, D. E. Sturdevant,, K. R. Braughton,, A. R. Whitney,, M. Otto,, and F. R. DeLeo. 2009. The SaeR/S gene regulatory system is essential for innate immune evasion by Staphylococcus aureus. J. Infect. Dis. 199:16981706.
165. Vuong, C.,, S. Kocianova,, Y. Yao,, A. B. Carmody,, and M. Otto. 2004. Increased colonization of indwelling medical devices by quorum-sensing mutants of Staphylococcus epidermidis in vivo. J. Infect. Dis. 190:14981505.
166. Wang, R.,, K. R. Braughton,, D. Kretschmer,, T. H. Bach,, S. Y. Queck,, M. Li,, A. D. Kennedy,, D. W. Dorward,, S. J. Klebanoff,, A. Peschel,, F. R. DeLeo,, and M. Otto. 2007. Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat. Med. 13:15101514.
167. Watkins, R. L.,, K. B. Pallister,, and J. M. Voyich. 2011. The SaeR/S gene regulatory system induces a pro-inflammatory cytokine response during Staphylococcus aureus infection. PLoS One 6:e19939.
168. Weidenmaier, C.,, J. F. Kokai-Kun,, S. A. Kristian,, T. Chanturiya,, H. Kalbacher,, M. Gross,, G. Nicholson,, B. Neumeister,, J. J. Mond,, and A. Peschel. 2004. Role of teichoic acids in Staphylococcus aureus nasal colonization, a major risk factor in nosocomial infections. Nat. Med. 10:243245.
169. Weinrick, B.,, P. M. Dunman,, F. McAleese,, E. Murphy,, S. J. Projan,, Y. Fang,, and R. P. Novick. 2004. Effect of mild acid on gene expression in Staphylococcus aureus. J. Bacteriol. 186:84078423.
170. Wright, J. S., III,, R. Jin,, and R. P. Novick. 2005.Transient interference with staphylococcal quorum sensing blocks abscess formation. Proc. Natl. Acad. Sci. USA 102:16911696.
171. Wuster, A.,, and M. M. Babu. 2008. Conservation and evolutionary dynamics of the agr cell-to-cell communication system across firmicutes. J. Bacteriol. 190:743746.
172. Xiong, Y. Q.,, J. Willard,, M. R. Yeaman,, A. L. Cheung,, and A. S. Bayer. 2006. Regulation of Staphylococcus aureus alpha-toxin gene (hla) expression by agr, sarA, and sae in vitro and in experimental infective endocarditis. J. Infect. Dis. 194:12671275.
173. Zhang, L.,, L. Gray,, R. P. Novick,, and G. Ji. 2002. Transmembrane topology of AgrB, the protein involved in the post-translational modification of AgrD in Staphylococcus aureus. J. Biol. Chem. 277:3473634742.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error