RNAIII is one of the main intracellular effectors of the quorum-sensing system. It is a multifunctional RNA that encodes a small peptide, and its noncoding parts act as antisense RNAs to regulate the translation and/or the stability of mRNAs encoding transcriptional regulators, major virulence factors, and cell wall metabolism enzymes. In this review, we explain how regulatory proteins and RNAIII are embedded in complex regulatory circuits to express virulence factors in a dynamic and timely manner in response to stress and environmental and metabolic changes.


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Literature Cited

  1. Adhikari RP, Novick RP. 1.  2008. Regulatory organization of the staphylococcal sae locus. Microbiology 154:949–959 [Google Scholar]
  2. Alonzo FE. Torres VJ. 2.  III, 2014. The bicomponent pore-forming leucocidins of Staphylococcus aureus. Microbiol. Mol. Biol. Rev. 78:199–230 [Google Scholar]
  3. Arya R, Ravikumar R, Santhosh RS, Princy SA. 3.  2015. SarA based novel therapeutic candidate against Staphylococcus aureus associated with vascular graft infections. Front. Microbiol. 6:416 [Google Scholar]
  4. Audretsch C, Lopez D, Srivastava M, Wolz C, Dandekar T. 4.  2013. A semi-quantitative model of quorum-sensing in Staphylococcus aureus, approved by microarray meta-analyses and tested by mutation studies. Mol. Biosyst. 9:2665–80 [Google Scholar]
  5. Balaban N, Goldkorn T, Nhan RT, Dang LB, Scott S. 5.  et al. 1998. Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureus. Science 280:438–40 [Google Scholar]
  6. Balaban N, Novick RP. 6.  1995. Translation of RNAIII, the Staphylococcus aureus agr regulatory RNA molecule, can be activated by a 3′-end deletion. FEMS Microbiol. Lett. 133:155–61 [Google Scholar]
  7. Becker S, Frankel MB, Schneewind O, Missiakas D. 7.  2014. Release of protein A from the cell wall of Staphylococcus aureus. PNAS 111:1574–79 [Google Scholar]
  8. Beisel CL, Storz G. 8.  2010. Base pairing small RNAs and their roles in global regulatory networks. FEMS Microbiol. Rev. 34:866–82 [Google Scholar]
  9. Benito Y, Kolb FA, Romby P, Lina G, Etienne J, Vandenesch F. 9.  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 6:668–79 [Google Scholar]
  10. Bischoff M, Dunman P, Kormanec J, Macapagal D, Murphy E. 10.  et al. 2004. Microarray-based analysis of the Staphylococcus aureus σB regulon. J. Bacteriol. 186:4085–99 [Google Scholar]
  11. Bischoff M, Entenza JM, Giachino P. 11.  2001. Influence of a functional sigB operon on the global regulators sar and agr in Staphylococcus aureus. J. Bacteriol. 183:5171–79 [Google Scholar]
  12. Bohn C, Rigoulay C, Chabelskaya S, Sharma CM, Marchais A. 12.  et al. 2010. Experimental discovery of small RNAs in Staphylococcus aureus reveals a riboregulator of central metabolism. Nucleic Acids Res. 38:6620–36 [Google Scholar]
  13. Boisset S, Geissmann T, Huntzinger E, Fechter P, Bendridi N. 13.  et al. 2007. Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism. Genes Dev. 21:1353–66 [Google Scholar]
  14. Carnes EC, Lopez DM, Donegan NP, Cheung A, Gresham H. 14.  et al. 2010. Confinement-induced quorum sensing of individual Staphylococcus aureus bacteria. Nat. Chem. Biol. 6:41–45 [Google Scholar]
  15. Cegelski L, Marshall GR, Eldridge GR, Hultgren SJ. 15.  2008. The biology and future prospects of antivirulence therapies. Nat. Rev. Microbiol. 6:17–27 [Google Scholar]
  16. Chabelskaya S, Bordeau V, Felden B. 16.  2014. Dual RNA regulatory control of a Staphylococcus aureus virulence factor. Nucleic Acids Res. 42:4847–58 [Google Scholar]
  17. Chabelskaya S, Gaillot O, Felden B. 17.  2010. A Staphylococcus aureus small RNA is required for bacterial virulence and regulates the expression of an immune-evasion molecule. PLOS Pathog. 6:e1000927 [Google Scholar]
  18. Cheung AL, Nishina KA, Trotonda MP, Tamber S. 18.  2008. The SarA protein family of Staphylococcus aureus. Int. J. Biochem. Cell Biol. 40:355–61 [Google Scholar]
  19. Cheung GY, Joo HS, Chatterjee SS, Otto M. 19.  2014. Phenol-soluble modulins—critical determinants of staphylococcal virulence. FEMS Microbiol. Rev. 38:698–719 [Google Scholar]
  20. Cheung GY, Kretschmer D, Duong AC, Yeh AJ, Ho TV. 20.  et al. 2014. Production of an attenuated phenol-soluble modulin variant unique to the MRSA clonal complex 30 increases severity of bloodstream infection. PLOS Pathog. 10:e1004298 [Google Scholar]
  21. Cheung GY, Villaruz AE, Joo HS, Duong AC, Yeh AJ. 21.  et al. 2014. Genome-wide analysis of the regulatory function mediated by the small regulatory psm-mec RNA of methicillin-resistant Staphylococcus aureus. Int. J. Med. Microbiol. 304:637–44 [Google Scholar]
  22. Chevalier C, Boisset S, Romilly C, Masquida B, Fechter P. 22.  et al. 2010. Staphylococcus aureus RNAIII binds to two distant regions of coa mRNA to arrest translation and promote mRNA degradation. PLOS Pathog. 6:e1000809 [Google Scholar]
  23. Chunhua M, Yu L, Yaping G, Jie D, Qiang L. 23.  et al. 2012. The expression of LytM is down-regulated by RNAIII in Staphylococcus aureus. J. Basic Microbiol. 52:636–41 [Google Scholar]
  24. Crosby HA, Schlievert PM, Merriman JA, King JM, Salgado-Pabon W, Horswill AR. 24.  2016. The Staphylococcus aureus global regulator MgrA modulates clumping and virulence by controlling surface protein expression. PLOS Pathog. 4:e1005604 [Google Scholar]
  25. Dubrac S, Msadek T. 25.  2008. Tearing down the wall: peptidoglycan metabolism and the WalK/WalR (YycG/YycF) essential two-component system. Adv. Exp. Med. Biol. 631:214–28 [Google Scholar]
  26. Dufour P, Jarraud S, Vandenesch F, Greenland T, Novick RP. 26.  et al. 2002. High genetic variability of the agr locus in Staphylococcus species. J. Bacteriol. 184:1180–86 [Google Scholar]
  27. Durand S, Braun F, Lioliou E, Romilly C, Helfer AC. 27.  et al. 2015. A nitric oxide regulated small rna controls expression of genes involved in redox homeostasis in Bacillus subtilis. PLOS Genet. 11:e1004957 [Google Scholar]
  28. Felden B, Vandenesch F, Bouloc P, Romby P. 28.  2011. The Staphylococcus aureus RNome and its commitment to virulence. PLOS Pathog. 7:e1002006 [Google Scholar]
  29. Fowler VGJ, Sakoulas G, McIntyre LM, Meka VG, Arbeit RD. 29.  et al. 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. 190:1140–49 [Google Scholar]
  30. Gagnaire J, Dauwalder O, Boisset S, Khau D, Freydiere AM. 30.  et al. 2012. Detection of Staphylococcus aureus delta-toxin production by whole-cell MALDI-TOF mass spectrometry. PLOS ONE 7:e40660 [Google Scholar]
  31. Geiger T, Goerke C, Mainiero M, Kraus D, Wolz C. 31.  2008. The virulence regulator Sae of Staphylococcus aureus: promoter activities and response to phagocytosis-related signals. J. Bacteriol. 190:3419–28 [Google Scholar]
  32. Geisinger E, Adhikari RP, Jin R, Ross HF, Novick RP. 32.  2006. Inhibition of rot translation by RNAIII, a key feature of agr function. Mol. Microbiol. 61:1038–48 [Google Scholar]
  33. Geisinger E, Chen J, Novick RP. 33.  2012. Allele-dependent differences in quorum-sensing dynamics result in variant expression of virulence genes in Staphylococcus aureus. J. Bacteriol. 194:2854–64 [Google Scholar]
  34. Geissmann T, Marzi S, Romby P. 34.  2009. A search for small noncoding RNAs in Staphylococcus aureus reveals a conserved sequence motif for regulation. Nucleic Acids Res. 37:7239–59 [Google Scholar]
  35. Germain E, Roghanian M, Gerdes K, Maisonneuve E. 35.  2015. Stochastic induction of persister cells by HipA through (p)ppGpp-mediated activation of mRNA endonucleases. PNAS 112:5171–76 [Google Scholar]
  36. Gomez MI, Lee A, Reddy B, Muir A, Soong G. 36.  et al. 2004. Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1. Nat. Med. 10:842–48 [Google Scholar]
  37. Goodyear CS, Silverman GJ. 37.  2004. Staphylococcal toxin induced preferential and prolonged in vivo deletion of innate-like B lymphocytes. PNAS 101:11392–97 [Google Scholar]
  38. Gordon CP, Williams P, Chan WC. 38.  2013. Attenuating Staphylococcus aureus virulence gene regulation: a medicinal chemistry perspective. J. Med. Chem. 56:1389–404 [Google Scholar]
  39. Gray B, Hall P, Gresham H. 39.  2013. Targeting agr- and agr-like quorum sensing systems for development of common therapeutics to treat multiple gram-positive bacterial infections. Sensors 13:5130–66 [Google Scholar]
  40. Gupta RK, Alba J, Xiong YQ, Bayer AS, Lee CY. 40.  2013. MgrA activates expression of capsule genes, but not the α-toxin gene in experimental Staphylococcus aureus endocarditis. J. Infect. Dis. 208:1841–48 [Google Scholar]
  41. Gupta RK, Luong TT, Lee CY. 41.  2015. RNAIII of the Staphylococcus aureus agr system activates global regulator MgrA by stabilizing mRNA. PNAS 112:14036–41 [Google Scholar]
  42. Hartmann T, Baronian G, Nippe N, Voss M, Schulthess B. 42.  et al. 2014. The catabolite control protein E (CcpE) affects virulence determinant production and pathogenesis of Staphylococcus aureus. J. Biol. Chem. 289:29701–11 [Google Scholar]
  43. Hoffman LR, Deziel E, D'Argenio DA, Lepine F, Emerson J. 43.  et al. 2006. Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa. PNAS 103:19890–95 [Google Scholar]
  44. Hsieh HY, Tseng CW, Stewart GC. 44.  2008. Regulation of Rot expression in Staphylococcus aureus. J. Bacteriol. 190:546–54 [Google Scholar]
  45. Huntzinger E, Boisset S, Saveanu C, Benito Y, Geissmann T. 45.  et al. 2005. Staphylococcus aureus RNAIII and the endoribonuclease III coordinately regulate spa gene expression. EMBO J. 24:824–35 [Google Scholar]
  46. Ibarra JA, Perez-Rueda E, Carroll RK, Shaw LN. 46.  2013. Global analysis of transcriptional regulators in Staphylococcus aureus. BMC Genomics 14:126 [Google Scholar]
  47. Ingavale S, van Wamel W, Luong TT, Lee CY, Cheung AL. 47.  2005. Rat/MgrA, a regulator of autolysis, is a regulator of virulence genes in Staphylococcus aureus. Infect. Immun. 73:1423–31 [Google Scholar]
  48. Janzon L, Arvidson S. 48.  1990. The role of the δ-lysin gene (hld) in the regulation of virulence genes by the accessory gene regulator (agr) in Staphylococcus aureus. EMBO J. 9:1391–99 [Google Scholar]
  49. Jarraud S, Lyon GJ, Figueiredo AM, Lina G, Vandenesch F. 49.  et al. 2000. Exfoliatin-producing strains define a fourth agr specificity group in Staphylococcus aureus. J. Bacteriol. 182:6517–22 [Google Scholar]
  50. Jelsbak L, Hemmingsen L, Donat S, Ohlsen K, Boye K. 50.  et al. 2010. Growth phase-dependent regulation of the global virulence regulator Rot in clinical isolates of Staphylococcus aureus. Int. J. Med. Microbiol. 300:229–36 [Google Scholar]
  51. Ji G, Beavis R, Novick RP. 51.  1997. Bacterial interference caused by autoinducing peptide variants. Science 276:2027–30 [Google Scholar]
  52. Kaito C, Saito Y, Ikuo M, Omae Y, Mao H. 52.  et al. 2013. Mobile genetic element SCCmec-encoded psm-mec RNA suppresses translation of agrA and attenuates MRSA virulence. PLOS Pathog. 9e1003269
  53. Kinkel TL, Roux CM, Dunman PM, Fang FC. 53.  2013. The Staphylococcus aureus SrrAB two-component system promotes resistance to nitrosative stress and hypoxia. mBio 4:e00696–13 [Google Scholar]
  54. Kobayashi SD, Malachowa N, Whitney AR, Braughton KR, Gardner DJ. 54.  et al. 2011. Comparative analysis of USA300 virulence determinants in a rabbit model of skin and soft tissue infection. J. Infect. Dis. 204:937–41 [Google Scholar]
  55. Koch G, Yepes A, Forstner KU, Wermser C, Stengel ST. 55.  et al. 2014. Evolution of resistance to a last-resort antibiotic in Staphylococcus aureus via bacterial competition. Cell 158:1060–71 [Google Scholar]
  56. Kolar SL, Ibarra JA, Rivera FE, Mootz JM, Davenport JE. 56.  et al. 2013. Extracellular proteases are key mediators of Staphylococcus aureus virulence via the global modulation of virulence-determinant stability. MicrobiologyOpen 2:18–34 [Google Scholar]
  57. Lasa I, Toledo-Arana A, Dobin A, Villanueva M. Mozos IR. 57. , de Los et al. 2011. Genome-wide antisense transcription drives mRNA processing in bacteria. PNAS 108:20172–77 [Google Scholar]
  58. Le KY, Otto M. 58.  2015. Quorum-sensing regulation in staphylococci—an overview. Front. Microbiol. 6:1174 [Google Scholar]
  59. Lee HH, Molla MN, Cantor CR, Collins JJ. 59.  2010. Bacterial charity work leads to population-wide resistance. Nature 467:82–85 [Google Scholar]
  60. Li D, Cheung A. 60.  2008. Repression of hla by rot is dependent on sae in Staphylococcus aureus. Infect. Immun. 76:1068–75 [Google Scholar]
  61. Li M, Cheung GY, Hu J, Wang D, Joo HS. 61.  et al. 2010. Comparative analysis of virulence and toxin expression of global community-associated methicillin-resistant Staphylococcus aureus strains. J. Infect. Dis. 202:1866–76 [Google Scholar]
  62. Lioliou E, Fechter P, Caldelari I, Jester BC, Dubrac S. 62.  et al. 2016. Various checkpoints prevent the synthesis of Staphylococcus aureus peptidoglycan hydrolase LytM in the stationary growth phase. RNA Biol. 13:427–40 [Google Scholar]
  63. Lioliou E, Sharma CM, Caldelari I, Helfer AC, Fechter P. 63.  et al. 2012. Global regulatory functions of the Staphylococcus aureus endoribonuclease III in gene expression. PLOS Genet. 8:e1002782 [Google Scholar]
  64. Liu Y, Mu C, Ying X, Li W, Wu N. 64.  et al. 2011. RNAIII activates map expression by forming an RNA-RNA complex in Staphylococcus aureus. FEBS Lett. 585:899–905 [Google Scholar]
  65. Lowy FD. 65.  1998. Staphylococcus aureus infections. New Engl. J. Med. 339:520–32 [Google Scholar]
  66. Luong TT, Dunman PM, Murphy E, Projan SJ, Lee CY. 66.  2006. Transcription profiling of the mgrA regulon in Staphylococcus aureus. J. Bacteriol. 188:1899–910 [Google Scholar]
  67. Lyon GJ, Wright JS, Muir TW, Novick RP. 67.  2002. Key determinants of receptor activation in the agr autoinducing peptides of Staphylococcus aureus. Biochemistry 41:10095–104 [Google Scholar]
  68. Mäder U, Nicolas P, Depke M, Pané-Farré J, Debarbouille M. 68.  et al. 2016. Staphylococcus aureus transcriptome architecture: from laboratory to infection mimicking conditions. PLOS Genet. 12:e1005962 [Google Scholar]
  69. Mainiero M, Goerke C, Geiger T, Gonser C, Herbert S, Wolz C. 69.  2010. Differential target gene activation by the Staphylococcus aureus two-component system saeRS. J. Bacteriol. 192:613–23 [Google Scholar]
  70. Majerczyk CD, Sadykov MR, Luong TT, Lee C, Somerville GA, Sonenshein AL. 70.  2008. Staphylococcus aureus CodY negatively regulates virulence gene expression. J. Bacteriol. 190:2257–65 [Google Scholar]
  71. Manna AC, Cheung AL. 71.  2003. sarU, a sarA homolog, is repressed by SarT and regulates virulence genes in Staphylococcus aureus. Infect. Immun. 71:343–53 [Google Scholar]
  72. Meier S, Goerke C, Wolz C, Seidl K, Homerova D. 72.  et al. 2007. σB and the σB-dependent arlRS and yabJ-spoVG loci affect capsule formation in Staphylococcus aureus. Infect. Immun. 75:4562–71 [Google Scholar]
  73. Messina JA, Thaden JT, Sharma-Kuinkel BK, Fowler VGJ. 73.  2016. Impact of bacterial and human genetic variation on Staphylococcus aureus infections. PLOS Pathog. 12:e1005330 [Google Scholar]
  74. Montgomery CP, Boyle-Vavra S, Adem PV, Lee JC, Husain AN. 74.  et al. 2008. Comparison of virulence in community-associated methicillin-resistant Staphylococcus aureus pulsotypes USA300 and USA400 in a rat model of pneumonia. J. Infect. Dis. 198:561–70 [Google Scholar]
  75. Montgomery CP, Boyle-Vavra S, Daum RS. 75.  2010. Importance of the global regulators Agr and SaeRS in the pathogenesis of CA-MRSA USA300 infection. PLOS ONE 5:e15177 [Google Scholar]
  76. Morfeldt E, Taylor D, von Gabain A, Arvidson S. 76.  1995. Activation of alpha-toxin translation in Staphylococcus aureus by the trans-encoded antisense RNA, RNAIII. EMBO J. 14:4569–77 [Google Scholar]
  77. Münzenmayer L, Geiger T, Daiber E, Schulte B, Autenrieth SE. 77.  et al. 2016. Influence of Sae-regulated and Agr-regulated factors on the escape of Staphylococcus aureus from human macrophages. Cell Microbiol. In press. doi: 10.1111/cmi.12577
  78. Nitzan M, Fechter P, Peer A, Altuvia Y, Bronesky D. 78.  et al. 2015. A defense-offense multi-layered regulatory switch in a pathogenic bacterium. Nucleic Acids Res. 43:1357–69 [Google Scholar]
  79. Nouaille S, Rault L, Jeanson S, Loubiere P, Le Loir Y, Even S. 79.  2014. Contribution of Lactococcus lactis reducing properties to the downregulation of a major virulence regulator in Staphylococcus aureus, the agr system. Appl. Environ. Microbiol. 80:7028–35 [Google Scholar]
  80. Novick RP. 80.  2003. Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol. Microbiol. 48:1429–49 [Google Scholar]
  81. Novick RP, Christie GE, Penades JR. 81.  2010. The phage-related chromosomal islands of gram-positive bacteria. Nat. Rev. Microbiol. 8:541–51 [Google Scholar]
  82. Novick RP, Geisinger E. 82.  2008. Quorum sensing in staphylococci. Annu. Rev. Genet. 42:541–64 [Google Scholar]
  83. Novick RP, Jiang D. 83.  2003. The staphylococcal saeRS system coordinates environmental signals with agr quorum sensing. Microbiology 149:2709–17 [Google Scholar]
  84. Novick RP, Ross HF, Projan SJ, Kornblum J, Kreiswirth B, Moghazeh S. 84.  1993. Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J. 12:3967–75 [Google Scholar]
  85. O'Keeffe KM, Wilk MM, Leech JM, Murphy AG, Laabei M. 85.  et al. 2015. Manipulation of autophagy in phagocytes facilitates Staphylococcus aureus bloodstream infection. Infect. Immun. 83:3445–57 [Google Scholar]
  86. Oscarsson J, Tegmark-Wisell K, Arvidson S. 86.  2006. Coordinated and differential control of aureolysin (aur) and serine protease (sspA) transcription in Staphylococcus aureus by sarA, rot and agr (RNAIII). Int. J. Med. Microbiol. 296:365–80 [Google Scholar]
  87. Otto M. 87.  2010. Staphylococcus aureus toxin gene hitchhikes on a transferable antibiotic resistance element. Virulence 1:49–51 [Google Scholar]
  88. Otto M. 88.  2014. Staphylococcus aureus toxins. Curr. Opin. Microbiol. 17:32–37 [Google Scholar]
  89. Oun S, Redder P, Didier JP, Francois P, Corvaglia AR. 89.  et al. 2013. The CshA DEAD-box RNA helicase is important for quorum sensing control in Staphylococcus aureus. RNA Biol. 10:157–65 [Google Scholar]
  90. Pagels M, Fuchs S, Pane-Farre J, Kohler C, Menschner L. 90.  et al. 2010. Redox sensing by a Rex-family repressor is involved in the regulation of anaerobic gene expression in Staphylococcus aureus. Mol. Microbiol. 76:1142–61 [Google Scholar]
  91. Painter KL, Krishna A, Wigneshweraraj S, Edwards AM. 91.  2014. What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?. Trends Microbiol. 22:676–85 [Google Scholar]
  92. Park J, Jagasia R, Kaufmann GF, Mathison JC, Ruiz DI. 92.  et al. 2007. Infection control by antibody disruption of bacterial quorum sensing signaling. Chem. Biol. 14:1119–27 [Google Scholar]
  93. Paspaliari DK, Mollerup MS, Kallipolitis BH, Ingmer H, Larsen MH. 93.  2014. Chitinase expression in Listeria monocytogenes is positively regulated by the Agr system. PLOS ONE 9:e95385 [Google Scholar]
  94. Pauli NT, Kim HK, Falugi F, Huang M, Dulac J. 94.  et al. 2014. Staphylococcus aureus infection induces protein A-mediated immune evasion in humans. J. Exp. Med. 211:2331–39 [Google Scholar]
  95. Pollitt EJ, West SA, Crusz SA, Burton-Chellew MN, Diggle SP. 95.  2014. Cooperation, quorum sensing, and evolution of virulence in Staphylococcus aureus. Infect. Immun. 82:1045–51 [Google Scholar]
  96. Powers ME, Wardenburg JB. 96.  2014. Igniting the fire: Staphylococcus aureus virulence factors in the pathogenesis of sepsis. PLOS Pathog. 10:e1003871 [Google Scholar]
  97. Pragman AA, Ji Y, Schlievert PM. 97.  2007. Repression of Staphylococcus aureus SrrAB using inducible antisense srrA alters growth and virulence factor transcript levels. Biochemistry 46:314–21 [Google Scholar]
  98. Proctor RA, Kriegeskorte A, Kahl BC, Becker K, Loffler B, Peters G. 98.  2014. Staphylococcus aureus small colony variants (SCVs): a road map for the metabolic pathways involved in persistent infections. Front. Cell Infect. Microbiol. 4:99 [Google Scholar]
  99. Qazi S, Middleton B, Muharram SH, Cockayne A, Hill P. 99.  et al. 2006. N-acylhomoserine lactones antagonize virulence gene expression and quorum sensing in Staphylococcus aureus. Infect. Immun. 74:910–19 [Google Scholar]
  100. Queck SY, Jameson-Lee M, Villaruz AE, Bach TH, Khan BA. 100.  et al. 2008. RNAIII-independent target gene control by the agr quorum-sensing system: insight into the evolution of virulence regulation in Staphylococcus aureus. Mol. Cell 32:150–58 [Google Scholar]
  101. Regassa LB, Novick RP, Betley MJ. 101.  1992. Glucose and nonmaintained pH decrease expression of the accessory gene regulator (agr) in Staphylococcus aureus. Infect. Immun. 60:3381–88 [Google Scholar]
  102. Reid G, Bruce AW. 102.  2001. Selection of Lactobacillus strains for urogenital probiotic applications. J. Infect. Dis. 183:Suppl. 1S77–80 [Google Scholar]
  103. Reyes D, Andrey DO, Monod A, Kelley WL, Zhang G, Cheung AL. 103.  2011. Coordinated regulation by AgrA, SarA, and SarR to control agr expression in Staphylococcus aureus. J. Bacteriol. 193:6020–31 [Google Scholar]
  104. Rieu A, Weidmann S, Garmyn D, Piveteau P, Guzzo J. 104.  2007. agr system of Listeria monocytogenes EGD-e: role in adherence and differential expression pattern. Appl. Environ. Microbiol. 73:6125–33 [Google Scholar]
  105. Romilly C, Lays C, Tomasini A, Caldelari I, Benito Y. 105.  et al. 2014. A non-coding RNA promotes bacterial persistence and decreases virulence by regulating a regulator in Staphylococcus aureus. PLOS Pathog. 10:e1003979 [Google Scholar]
  106. Rudkin JK, Edwards AM, Bowden MG, Brown EL, Pozzi C. 106.  et al. 2012. Methicillin resistance reduces the virulence of healthcare-associated methicillin-resistant Staphylococcus aureus by interfering with the agr quorum sensing system. J. Infect. Dis. 205:798–806 [Google Scholar]
  107. Said-Salim B, Dunman PM, McAleese FM, Macapagal D, Murphy E. 107.  et al. 2003. Global regulation of Staphylococcus aureus genes by Rot. J. Bacteriol. 185:610–19 [Google Scholar]
  108. Sakoulas G, Eliopoulos GM, Moellering RCJ, Wennersten C, Venkataraman L. 108.  et al. 2002. Accessory gene regulator (agr) locus in geographically diverse Staphylococcus aureus isolates with reduced susceptibility to vancomycin. Antimicrob. Agents Chemother. 46:1492–502 [Google Scholar]
  109. Schmidt KA, Manna AC, Cheung AL. 109.  2003. SarT influences sarS expression in Staphylococcus aureus. Infect. Immun. 71:5139–48 [Google Scholar]
  110. Schmidt KA, Manna AC, Gill S, Cheung AL. 110.  2001. SarT, a repressor of α-hemolysin in Staphylococcus aureus. Infect. Immun. 69:4749–58 [Google Scholar]
  111. Schwan WR, Langhorne MH, Ritchie HD, Stover CK. 111.  2003. Loss of hemolysin expression in Staphylococcus aureus agr mutants correlates with selective survival during mixed infections in murine abscesses and wounds. FEMS Immunol. Med. Microbiol. 38:23–28 [Google Scholar]
  112. Seidl K, Stucki M, Ruegg M, Goerke C, Wolz C. 112.  et al. 2006. Staphylococcus aureus CcpA affects virulence determinant production and antibiotic resistance. Antimicrob. Agents Chemother. 50:1183–94 [Google Scholar]
  113. Shopsin B, Drlica-Wagner A, Mathema B, Adhikari RP, Kreiswirth BN, Novick RP. 113.  2008. Prevalence of agr dysfunction among colonizing Staphylococcus aureus strains. J. Infect. Dis. 198:1171–74 [Google Scholar]
  114. Shopsin B, Eaton C, Wasserman GA, Mathema B, Adhikari RP. 114.  et al. 2010. Mutations in agr do not persist in natural populations of methicillin-resistant Staphylococcus aureus. J. Infect. Dis. 202:1593–99 [Google Scholar]
  115. Somerville GA, Proctor RA. 115.  2009. At the crossroads of bacterial metabolism and virulence factor synthesis in Staphylococci. Microbiol. Mol. Biol. Rev. 73:233–48 [Google Scholar]
  116. Song J, Lays C, Vandenesch F, Benito Y, Bes M. 116.  et al. 2012. The expression of small regulatory RNAs in clinical samples reflects the different life styles of Staphylococcus aureus in colonization versus infection. PLOS ONE 7:e37294 [Google Scholar]
  117. Stock AM, Robinson VL, Goudreau PN. 117.  2000. Two-component signal transduction. Annu. Rev. Biochem. 69:183–215 [Google Scholar]
  118. Sully EK, Malachowa N, Elmore BO, Alexander SM, Femling JK. 118.  et al. 2014. Selective chemical inhibition of agr quorum sensing in Staphylococcus aureus promotes host defense with minimal impact on resistance. PLOS Pathog. 10:e1004174 [Google Scholar]
  119. Thoendel M, Kavanaugh JS, Flack CE, Horswill AR. 119.  2011. Peptide signaling in the staphylococci. Chem. Rev. 111:117–51 [Google Scholar]
  120. Tomasini A, Francois P, Howden BP, Fechter P, Romby P, Caldelari I. 120.  2014. The importance of regulatory RNAs in Staphylococcus aureus. Infect. Genet. Evol. 21:616–26 [Google Scholar]
  121. Traber KE, Lee E, Benson S, Corrigan R, Cantera M. 121.  et al. 2008. agr function in clinical Staphylococcus aureus isolates. Microbiology 154:2265–74 [Google Scholar]
  122. Trotonda MP, Tamber S, Memmi G, Cheung AL. 122.  2008. MgrA represses biofilm formation in Staphylococcus aureus. Infect. Immun. 76:5645–54 [Google Scholar]
  123. Tuchscherr L, Bischoff M, Lattar SM, Noto Llana M, Pfortner H. 123.  et al. 2015. Sigma factor SigB is crucial to mediate Staphylococcus aureus adaptation during chronic infections. PLOS Pathog. 11:e1004870 [Google Scholar]
  124. Tuchscherr L, Loffler B. 124.  2016. Staphylococcus aureus dynamically adapts global regulators and virulence factor expression in the course from acute to chronic infection. Curr. Genet. 62:15–17 [Google Scholar]
  125. Turner RD, Vollmer W, Foster SJ. 125.  2014. Different walls for rods and balls: the diversity of peptidoglycan. Mol. Microbiol. 91:862–74 [Google Scholar]
  126. Vivant AL, Garmyn D, Gal L, Hartmann A, Piveteau P. 126.  2015. Survival of Listeria monocytogenes in soil requires AgrA-mediated regulation. Appl. Environ. Microbiol. 81:5073–84 [Google Scholar]
  127. Wertheim HF, Vos MC, Ott A, van Belkum A, Voss A. 127.  et al. 2004. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet 364:703–5 [Google Scholar]
  128. Westermann AJ, Forstner KU, Amman F, Barquist L, Chao Y. 128.  et al. 2016. Dual RNA-seq unveils noncoding RNA functions in host–pathogen interactions. Nature 529:496–501 [Google Scholar]
  129. Westermann AJ, Gorski SA, Vogel J. 129.  2012. Dual RNA-seq of pathogen and host. Nat. Rev. Microbiol. 10:618–30 [Google Scholar]
  130. Xue T, Zhang X, Sun H, Sun B. 130.  2014. ArtR, a novel sRNA of Staphylococcus aureus, regulates α-toxin expression by targeting the 5′ UTR of sarT mRNA. Med. Microbiol. Immunol. 203:1–12 [Google Scholar]
  131. Zecconi A, Scali F. 131.  2013. Staphylococcus aureus virulence factors in evasion from innate immune defenses in human and animal diseases. Immunol. Lett. 150:12–22 [Google Scholar]
  132. Zhu Y, Nandakumar R, Sadykov MR, Madayiputhiya N, Luong TT. 132.  et al. 2011. RpiR homologues may link Staphylococcus aureus RNAIII synthesis and pentose phosphate pathway regulation. J. Bacteriol. 193:6187–96 [Google Scholar]
  133. Zielinska AK, Beenken KE, Joo HS, Mrak LN, Griffin LM. 133.  et al. 2011. Defining the strain-dependent impact of the staphylococcal accessory regulator (sarA) on the alpha-toxin phenotype of Staphylococcus aureus. J. Bacteriol. 193:2948–58 [Google Scholar]

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