1887

Microbiology Society logo

Volume 169, Issue 8

Quorum-sensing, intra- and inter-species competition in the staphylococci Open Access

Abstract

In Gram-positive bacteria such as and the coagulase-negative staphylococci (CoNS), the accessory gene regulator () is a highly conserved but polymorphic quorum-sensing system involved in colonization, virulence and biofilm development. Signalling via depends on the interaction of an autoinducing peptide (AIP) with AgrC, a transmembrane sensor kinase that, once phosphorylated activates the response regulator AgrA. This in turn autoinduces AIP biosynthesis and drives target gene expression directly via AgrA or via the post-transcriptional regulator, RNAIII. In this review we describe the molecular mechanisms underlying the -mediated generation of, and response to, AIPs and the molecular basis of AIP-dependent activation and inhibition of AgrC. How the environment impacts on functionality is considered and the consequences of dysfunction for infection explored. We also discuss the concept of AIP-driven competitive interference between and the CoNS and its anti-infective potential.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): agr , autoinducing peptides , inter-bacterial competition , quorum sensing , staphylococci and Staphylococcus aureus
Funding
This study was supported by the:
  • Medical Research Council (Award MR/N010477/1)
    • Principle Award Recipient: PaulWilliams
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.001381
2023-08-14
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/micro/169/8/mic001381.html?itemId=/content/journal/micro/10.1099/mic.0.001381&mimeType=html&fmt=ahah

References

  1. Parlet CP, Brown MM, Horswill AR. Commensal Staphylococci influence Staphylococcus aureus skin colonization and disease. Trends Microbiol 2019; 27:497–507 [View Article] [PubMed]
     [Google Scholar]
  2. Peng P, Baldry M, Gless BH, Bojer MS, Espinosa-Gongora C et al. Effect of co-inhabiting coagulase negative Staphylococci on S. aureus agr quorum sensing, host factor binding, and biofilm formation. Front Microbiol 2019; 10:2212 [View Article] [PubMed]
     [Google Scholar]
  3. Cheung GYC, Bae JS, Otto M. Pathogenicity and virulence of Staphylococcus aureus. Virulence 2021; 12:547–569 [View Article] [PubMed]
     [Google Scholar]
  4. Chambers HF, Deleo FR. Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol 2009; 7:629–641 [View Article] [PubMed]
     [Google Scholar]
  5. Nair N, Biswas R, Götz F, Biswas L. Impact of Staphylococcus aureus on pathogenesis in polymicrobial infections. Infect Immun 2014; 82:2162–2169 [View Article] [PubMed]
     [Google Scholar]
  6. Orazi G, O’Toole GA. “It takes a village”: mechanisms underlying antimicrobial recalcitrance of polymicrobial biofilms. J Bacteriol 2019; 202:e00530-19 [View Article] [PubMed]
     [Google Scholar]
  7. Kavanaugh JS, Horswill AR. Impact of environmental cues on Staphylococcal quorum sensing and biofilm development. J Biol Chem 2016; 291:12556–12564 [View Article] [PubMed]
     [Google Scholar]
  8. Balasubramanian D, Harper L, Shopsin B, Torres VJ. Staphylococcus aureus pathogenesis in diverse host environments. Pathog Dis 2017; 75:ftx005 [View Article] [PubMed]
     [Google Scholar]
  9. Purves J, Hussey SJK, Corscadden L, Purser L, Hall A et al. Air pollution induces Staphylococcus aureus USA300 respiratory tract colonization mediated by specific bacterial genetic responses involving the global virulence gene regulators Agr and Sae. Environ Microbiol 2022; 24:4449–4465 [View Article] [PubMed]
     [Google Scholar]
  10. Williams P, Winzer K, Chan WC, Cámara M. Look who’s talking: communication and quorum sensing in the bacterial world. Philos Trans R Soc Lond B Biol Sci 2007; 362:1119–1134 [View Article] [PubMed]
     [Google Scholar]
  11. Gray B, Hall P, Gresham H. Targeting agr- and agr-like quorum sensing systems for development of common therapeutics to treat multiple gram-positive bacterial infections. Sensors 2013; 13:5130–5166 [View Article] [PubMed]
     [Google Scholar]
  12. Darkoh C, DuPont HL, Norris SJ, Kaplan HB. Toxin synthesis by Clostridium difficile is regulated through quorum signaling. mBio 2015; 6:e02569 [View Article] [PubMed]
     [Google Scholar]
  13. Nizet V. Understanding how leading bacterial pathogens subvert innate immunity to reveal novel therapeutic targets. J Allergy Clin Immunol 2007; 120:13–22 [View Article] [PubMed]
     [Google Scholar]
  14. Qazi SN, Counil E, Morrissey J, Rees CE, Cockayne A et al. agr expression precedes escape of internalized Staphylococcus aureus from the host endosome. Infect Immun 2001; 69:7074–7082 [View Article] [PubMed]
     [Google Scholar]
  15. Rothfork JM, Timmins GS, Harris MN, Chen X, Lusis AJ 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 [View Article] [PubMed]
     [Google Scholar]
  16. Pang YY, Schwartz J, Thoendel M, Ackermann LW, Horswill AR et al. agr-dependent interactions of Staphylococcus aureus USA300 with human polymorphonuclear neutrophils. J Innate Immun 2010; 2:546–559 [View Article] [PubMed]
     [Google Scholar]
  17. Schilcher K, Horswill AR. Staphylococcal biofilm development: structure, regulation, and treatment strategies. Microbiol Mol Biol Rev 2020; 84:e00026-19 [View Article] [PubMed]
     [Google Scholar]
  18. Otto M. Critical assessment of the prospects of quorum-quenching therapy for Staphylococcus aureus infection. Int J Mol Sci 2023; 24:4025 [View Article] [PubMed]
     [Google Scholar]
  19. Nakamura Y, Takahashi H, Takaya A, Inoue Y, Katayama Y et al. Staphylococcus agr virulence is critical for epidermal colonization and associates with atopic dermatitis development. Sci Transl Med 2020; 12:eaay4068 [View Article] [PubMed]
     [Google Scholar]
  20. Novick RP, Geisinger E. Quorum sensing in Staphylococci. Annu Rev Genet 2008; 42:541–564 [View Article] [PubMed]
     [Google Scholar]
  21. Canovas J, Baldry M, Bojer MJ, Andersen PS, Grzeskowiak PK et al. Cross-talk between Staphylococcus aureus and other Staphylococcal species via the agr quorum sensing. Syst Front Microbiol 2016; 7:1733 [View Article] [PubMed]
     [Google Scholar]
  22. Horswill AR, Gordon CP. Structure-activity relationship studies of small molecule modulators of the staphylococcal accessory gene regulator. J Med Chem 2020; 63:2705–2730 [View Article] [PubMed]
     [Google Scholar]
  23. Jenul C, Horswill AR. Regulation of Staphylococcus aureus virulence. Microbiol Spectr 2019; 7: [View Article] [PubMed]
     [Google Scholar]
  24. Bronesky D, Wu Z, Marzi S, Walter P, Geissmann T et al. Staphylococcus aureus RNAIII and its regulon link quorum sensing, stress responses, metabolic adaptation, and regulation of virulence gene expression. Annu Rev Microbiol 2016; 70:299–316 [View Article] [PubMed]
     [Google Scholar]
  25. Wang B, Zhao A, Novick RP, Muir TW. Activation and inhibition of the receptor histidine kinase AgrC occurs through opposite helical transduction motions. Molecular Cell 2014; 53:929–940 [View Article] [PubMed]
     [Google Scholar]
  26. Ji G, Beavis RC, Novick RP. Cell density control of staphylococcal virulence mediated by an octapeptide pheromone. Proc Natl Acad Sci U S A 1995; 92:12055–12059 [View Article] [PubMed]
     [Google Scholar]
  27. Ji G, Beavis R, Novick RP. Bacterial interference caused by autoinducing peptide variants. Science 1997; 276:2027–2030 [View Article] [PubMed]
     [Google Scholar]
  28. McDowell P, Affas Z, Reynolds C, Holden MTG, Wood SJ et al. Structure, activity and evolution of the group I thiolactone peptide quorum-sensing system of Staphylococcus aureus. Mol Microbiol 2001; 41:503–512 [View Article] [PubMed]
     [Google Scholar]
  29. Lyon GJ, Wright JS, Muir TW, Novick RP. Key determinants of receptor activation in the agr autoinducing peptides of Staphylococcus aureus. Biochemistry 2002; 41:10095–10104 [View Article] [PubMed]
     [Google Scholar]
  30. Lyon GJ, Wright JS, Christopoulos A, Novick RP, Muir TW. Reversible and specific extracellular antagonism of receptor-histidine kinase signaling. J Biol Chem 2002; 277:6247–6253 [View Article] [PubMed]
     [Google Scholar]
  31. Jensen RO, Winzer K, Clarke SR, Chan WC, Williams P. Differential recognition of Staphylococcus aureus quorum-sensing signals depends on both extracellular loops 1 and 2 of the transmembrane sensor AgrC. J Mol Biol 2008; 381:300–309 [View Article] [PubMed]
     [Google Scholar]
  32. Raghuram V, Alexander AM, Loo HQ, Petit RA, Goldberg JB et al. Species-wide phylogenomics of the Staphylococcus aureus Agr operon revealed convergent evolution of frameshift mutations. Microbiol Spectr 2022; 10:e0133421 [View Article] [PubMed]
     [Google Scholar]
  33. Jarraud S, Mougel C, Thioulouse J, Lina G, Meugnier H et al. Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease. Infect Immun 2002; 70:631–641 [View Article] [PubMed]
     [Google Scholar]
  34. Lange J, Heidenreich K, Higelin K, Dyck K, Marx V et al. Staphylococcus aureus pathogenicity in cystic fibrosis patients-results from an observational prospective multicenter study concerning virulence genes, phylogeny, and gene plasticity. Toxins 2020; 12:279 [View Article] [PubMed]
     [Google Scholar]
  35. Kalkum M, Lyon GJ, Chait BT. Detection of secreted peptides by using hypothesis-driven multistage mass spectrometry. Proc Natl Acad Sci 2003; 100:2795–2800 [View Article] [PubMed]
     [Google Scholar]
  36. Junio HA, Todd DA, Ettefagh KA, Ehrmann BM, Kavanaugh JS et al. Quantitative analysis of autoinducing peptide I (AIP-I) from Staphylococcus aureus cultures using ultrahigh performance liquid chromatography-high resolving power mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2013; 930:7–12 [View Article] [PubMed]
     [Google Scholar]
  37. Gless BH, Bojer MS, Peng P, Baldry M, Ingmer H et al. Identification of autoinducing thiodepsipeptides from staphylococci enabled by native chemical ligation. Nat Chem 2019; 11:463–469 [View Article] [PubMed]
     [Google Scholar]
  38. Mayville P, Ji G, Beavis R, Yang H, Goger M et al. Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence. Proc Natl Acad Sci 1999; 96:1218–1223 [View Article] [PubMed]
     [Google Scholar]
  39. Malone CL, Boles BR, Horswill AR. Biosynthesis of Staphylococcus aureus autoinducing peptides by using the synechocystis DnaB mini-intein. Appl Environ Microbiol 2007; 73:6036–6044 [View Article] [PubMed]
     [Google Scholar]
  40. Malone CL, Boles BR, Lauderdale KJ, Thoendel M, Kavanaugh JS et al. Fluorescent reporters for Staphylococcus aureus. J Microbiol Methods 2009; 77:251–260 [View Article] [PubMed]
     [Google Scholar]
  41. Murray EJ, Williams P. Detection of Agr-type autoinducing peptides produced by Staphylococcus aureus. Methods Mol Biol 2018; 1673:89–96 [View Article] [PubMed]
     [Google Scholar]
  42. Blower I, Tong C, Sun X, Murray E, Luckett J et al. Gaussia Luciferase as a Reporter for Quorum Sensing in Staphylococcus aureus. Sensors 2020; 20:4305 [View Article] [PubMed]
     [Google Scholar]
  43. Zhang L, Ji G. Identification of a Staphylococcal AgrB segment(s) responsible for group-specific processing of AgrD by gene swapping. J Bacteriol 2004; 186:6706–6713 [View Article] [PubMed]
     [Google Scholar]
  44. Qiu R, Pei W, Zhang L, Lin J, Ji G. Identification of the putative Staphylococcal AgrB catalytic residues involving the proteolytic cleavage of AgrD to generate autoinducing peptide. J Biol Chem 2005; 280:16695–16704 [View Article] [PubMed]
     [Google Scholar]
  45. Thoendel M, Horswill AR. Identification of Staphylococcus aureus AgrD residues required for autoinducing peptide biosynthesis. J Biol Chem 2009; 284:21828–21838 [View Article] [PubMed]
     [Google Scholar]
  46. Wang B, Muir TW. Regulation of virulence in Staphylococcus aureus: molecular mechanisms and remaining puzzles. Cell Chem Biol 2016; 23:214–224 [View Article] [PubMed]
     [Google Scholar]
  47. Wang B, Zhao A, Novick RP, Muir TW. Key driving forces in the biosynthesis of autoinducing peptides required for Staphylococcal virulence. Proc Natl Acad Sci 2015; 112:10679–10684 [View Article] [PubMed]
     [Google Scholar]
  48. Frees D, Qazi SNA, Hill PJ, Ingmer H. Alternative roles of ClpX and ClpP in Staphylococcus aureus stress tolerance and virulence. Mol Microbiol 2003; 48:1565–1578 [View Article] [PubMed]
     [Google Scholar]
  49. Zhang L, Gray L, Novick RP, Ji G. Transmembrane topology of AgrB, the protein involved in the post-translational modification of AgrD in Staphylococcus aureus. J Biol Chem 2002; 277:34736–34742 [View Article] [PubMed]
     [Google Scholar]
  50. Thoendel M, Horswill AR. Random mutagenesis and topology analysis of the autoinducing peptide biosynthesis proteins in Staphylococcus aureus. Mol Microbiol 2013; 87:318–337 [View Article] [PubMed]
     [Google Scholar]
  51. Bardelang P, Murray EJ, Blower I, Zandomeneghi S, Goode A et al. Conformational analysis and interaction of the Staphylococcus aureus transmembrane peptidase AgrB with its AgrD propeptide substrate. Front Chem 2023; 11:1113885 [View Article] [PubMed]
     [Google Scholar]
  52. Kavanaugh JS, Thoendel M, Horswill AR. A role for type I signal peptidase in Staphylococcus aureus quorum sensing. Mol Microbiol 2007; 65:780–798 [View Article] [PubMed]
     [Google Scholar]
  53. Cosgriff CJ, White CR, Teoh WP, Grayczyk JP, Alonzo F. Control of Staphylococcus aureus quorum sensing by a membrane-embedded peptidase. Infect Immun 2019; 87:e00019-19 [View Article] [PubMed]
     [Google Scholar]
  54. Marroquin S, Gimza B, Tomlinson B, Stein M, Frey A et al. MroQ is a novel abi-domain protein that influences virulence gene expression in Staphylococcus aureus via modulation of agr activity. Infect Immun 2019; 87:e00002-19 [View Article] [PubMed]
     [Google Scholar]
  55. Pei J, Mitchell DA, Dixon JE, Grishin NV. Expansion of type II CAAX proteases reveals evolutionary origin of γ-secretase subunit APH-1. J Mol Biol 2011; 410:18–26 [View Article] [PubMed]
     [Google Scholar]
  56. Kjos M, Snipen L, Salehian Z, Nes IF, Diep DB. The Abi proteins and their involvement in bacteriocin self-immunity. J Bacteriol 2010; 192:2068–2076 [View Article] [PubMed]
     [Google Scholar]
  57. Firon A, Tazi A, Da Cunha V, Brinster S, Sauvage E et al. The Abi-domain protein Abx1 interacts with the CovS histidine kinase to control virulence gene expression in group B Streptococcus. PLoS Pathog 2013; 9:e1003179 [View Article] [PubMed]
     [Google Scholar]
  58. Stock MR, Fang L, Johnson KR, Cosgriff C, Teoh WP et al. Characterization of MroQ-dependent maturation and export of the Staphylococcus aureus accessory gene regulatory system autoinducing peptide. Infect Immun 2022; 90:e0026322 [View Article] [PubMed]
     [Google Scholar]
  59. Willing S, Schneewind O, Missiakas D. Regulated cleavage of glycan strands by the murein hydrolase SagB in S. aureus involves a direct interaction with LyrA (SpdC). J Bacteriol 2021; 203:e00014-21 [View Article] [PubMed]
     [Google Scholar]
  60. Schaefer K, Owens TW, Page JE, Santiago M, Kahne D et al. Structure and reconstitution of a hydrolase complex that may release peptidoglycan from the membrane after polymerization. Nat Microbiol 2021; 6:34–43 [View Article] [PubMed]
     [Google Scholar]
  61. Zhao A, Bodine SP, Xie Q, Wang B, Ram G et al. Reconstitution of the S. aureus agr quorum sensing pathway reveals a direct role for the integral membrane protease MroQ in pheromone biosynthesis. Proc Natl Acad Sci U S A 2022; 119:e2202661119 [View Article] [PubMed]
     [Google Scholar]
  62. Schwartz K, Sekedat MD, Syed AK, O’Hara B, Payne DE et al. The AgrD N-terminal leader peptide of Staphylococcus aureus has cytolytic and amyloidogenic properties. Infect Immun 2014; 82:3837–3844 [View Article] [PubMed]
     [Google Scholar]
  63. Gonzalez DJ, Corriden R, Akong-Moore K, Olson J, Dorrestein PC et al. N-terminal ArgD peptides from the classical Staphylococcus aureus Agr system have cytotoxic and proinflammatory activities. Chem Biol 2014; 21:1457–1462 [View Article] [PubMed]
     [Google Scholar]
  64. Dickey SW, Burgin DJ, Huang S, Maguire D, Otto M. Two transporters cooperate to secrete amphipathic peptides from the cytoplasmic and membranous milieus. Proc Natl Acad Sci 2023; 120:e2211689120 [View Article] [PubMed]
     [Google Scholar]
  65. Grebe TW, Stock JB. The histidine protein kinase superfamily. Adv Microb Physiol 1999; 41:139–227 [View Article] [PubMed]
     [Google Scholar]
  66. Srivastava SK, Rajasree K, Fasim A, Arakere G, Gopal B. Influence of the AgrC-AgrA complex on the response time of Staphylococcus aureus quorum sensing. J Bacteriol 2014; 196:2876–2888 [View Article] [PubMed]
     [Google Scholar]
  67. Xie Q, Zhao A, Jeffrey PD, Kim MK, Bassler BL et al. Identification of a molecular latch that regulates Staphylococcal virulence. Cell Chem Biol 2019; 26:548–558 [View Article] [PubMed]
     [Google Scholar]
  68. Geisinger E, George EA, Chen J, Muir TW, Novick RP. Identification of ligand specificity determinants in AgrC, the Staphylococcus aureus quorum-sensing receptor. J Biol Chem 2008; 283:8930–8938 [View Article] [PubMed]
     [Google Scholar]
  69. Geisinger E, Muir TW, Novick RP. agr receptor mutants reveal distinct modes of inhibition by staphylococcal autoinducing peptides. Proc Natl Acad Sci 2009; 106:1216–1221 [View Article] [PubMed]
     [Google Scholar]
  70. Nikolskaya AN, Galperin MY. A novel type of conserved DNA-binding domain in the transcriptional regulators of the AlgR/AgrA/LytR family. Nucleic Acids Res 2002; 30:2453–2459 [View Article] [PubMed]
     [Google Scholar]
  71. Sidote DJ, Barbieri CM, Wu T, Stock AM. Structure of the Staphylococcus aureus AgrA LytTR domain bound to DNA reveals a beta fold with an unusual mode of binding. Structure 2008; 16:727–735 [View Article] [PubMed]
     [Google Scholar]
  72. Reynolds J, Wigneshweraraj S. Molecular insights into the control of transcription initiation at the Staphylococcus aureus agr operon. J Mol Biol 2011; 412:862–881 [View Article] [PubMed]
     [Google Scholar]
  73. Queck SY, Jameson-Lee M, Villaruz AE, Bach T-HL, Khan BA 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 [View Article] [PubMed]
     [Google Scholar]
  74. Tal-Gan Y, Stacy DM, Foegen MK, Koenig DW, Blackwell HE. Highly potent inhibitors of quorum sensing in Staphylococcus aureus revealed through a systematic synthetic study of the group-III autoinducing peptide. J Am Chem Soc 2013; 135:7869–7882 [View Article] [PubMed]
     [Google Scholar]
  75. Tal-Gan Y, Ivancic M, Cornilescu G, Cornilescu CC, Blackwell HE. Structural characterization of native autoinducing peptides and abiotic analogues reveals key features essential for activation and inhibition of an AgrC quorum sensing receptor in Staphylococcus aureus. J Am Chem Soc 2013; 135:18436–18444 [View Article] [PubMed]
     [Google Scholar]
  76. Tal-Gan Y, Ivancic M, Cornilescu G, Blackwell HE. Characterization of structural elements in native autoinducing peptides and non-native analogues that permit the differential modulation of AgrC-type quorum sensing receptors in Staphylococcus aureus. Org Biomol Chem 2016; 14:113–121 [View Article] [PubMed]
     [Google Scholar]
  77. Tal-Gan Y, Ivancic M, Cornilescu G, Yang T, Blackwell HE. Highly stable, amide-bridged autoinducing peptide analogues that strongly inhibit the AgrC quorum sensing receptor in Staphylococcus aureus. Angew Chem Int Ed Engl 2016; 55:8913–8917 [View Article] [PubMed]
     [Google Scholar]
  78. Otto M, Süssmuth R, Vuong C, Jung G, Götz F. Inhibition of virulence factor expression in Staphylococcus aureus by the Staphylococcus epidermidis agr pheromone and derivatives. FEBS Lett 1999; 450:257–262 [View Article] [PubMed]
     [Google Scholar]
  79. Johnson JG, Wang B, Debelouchina GT, Novick RP, Muir TW. Increasing AIP macrocycle size reveals key features of agr activation in Staphylococcus aureus. Chembiochem 2015; 16:1093–1100 [View Article] [PubMed]
     [Google Scholar]
  80. Chan WC, Coyle BJ, Williams P. Virulence regulation and quorum sensing in Staphylococcal infections: competitive AgrC antagonists as quorum sensing inhibitors. J Med Chem 2004; 47:4633–4641 [View Article] [PubMed]
     [Google Scholar]
  81. García-Betancur J-C, Goñi-Moreno A, Horger T, Schott M, Sharan M et al. Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus. Elife 2017; 6:e28023 [View Article] [PubMed]
     [Google Scholar]
  82. Mukherjee S, Bassler BL. Bacterial quorum sensing in complex and dynamically changing environments. Nat Rev Microbiol 2019; 17:371–382 [View Article] [PubMed]
     [Google Scholar]
  83. Rudkin JK, Edwards AM, Bowden MG, Brown EL, Pozzi C 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 [View Article] [PubMed]
     [Google Scholar]
  84. Grundstad ML, Parlet CP, Kwiecinski JM, Kavanaugh JS, Crosby HA et al. Quorum sensing, virulence, and antibiotic resistance of USA100 methicillin-resistant Staphylococcus aureus isolates. mSphere 2019; 4:e00553-19 [View Article] [PubMed]
     [Google Scholar]
  85. Cheung GYC, Wang R, Khan BA, Sturdevant DE, Otto M. Role of the accessory gene regulator agr in community-associated methicillin-resistant Staphylococcus aureus pathogenesis. Infect Immun 2011; 79:1927–1935 [View Article] [PubMed]
     [Google Scholar]
  86. Geisinger E, Chen J, Novick RP. Allele-dependent differences in quorum-sensing dynamics result in variant expression of virulence genes in Staphylococcus aureus. J Bacteriol 2012; 194:2854–2864 [View Article] [PubMed]
     [Google Scholar]
  87. Sloan TJ, Murray E, Yokoyama M, Massey RC, Chan WC et al. Timing is everything: impact of naturally occurring Staphylococcus aureus AgrC cytoplasmic domain adaptive mutations on autoinduction. J Bacteriol 2019; 201:e00409-19 [View Article] [PubMed]
     [Google Scholar]
  88. Wright JS, Jin R, Novick RP. Transient interference with Staphylococcal quorum sensing blocks abscess formation. Proc Natl Acad Sci U S A 2005; 102:1691–1696 [View Article] [PubMed]
     [Google Scholar]
  89. Winson MK, Swift S, Hill PJ, Sims CM, Griesmayr G et al. Engineering the luxCDABE genes from Photorhabdus luminescens to provide a bioluminescent reporter for constitutive and promoter probe plasmids and mini-Tn 5 constructs. FEMS Microbiol Lett 1998; 163:193–202 [View Article] [PubMed]
     [Google Scholar]
  90. Sun F, Liang H, Kong X, Xie S, Cho H et al. Quorum-sensing agr mediates bacterial oxidation response via an intramolecular disulfide redox switch in the response regulator AgrA. Proc Natl Acad Sci USA 2012; 109:9095–9100 [View Article] [PubMed]
     [Google Scholar]
  91. Baković J, Yu BYK, Silva D, Baczynska M, Peak-Chew SY et al. Redox Regulation of the Quorum-sensing Transcription Factor AgrA by Coenzyme A. Antioxidants 2021; 10:841 [View Article] [PubMed]
     [Google Scholar]
  92. George SE, Hrubesch J, Breuing I, Vetter N, Korn N et al. Oxidative stress drives the selection of quorum sensing mutants in the Staphylococcus aureus population. Proc Natl Acad Sci U S A 2019; 116:19145–19154 [View Article] [PubMed]
     [Google Scholar]
  93. Peterson MM, Mack JL, Hall PR, Alsup AA, Alexander SM et al. Apolipoprotein B is an innate barrier against invasive Staphylococcus aureus infection. Cell Host Microbe 2008; 4:555–566 [View Article] [PubMed]
     [Google Scholar]
  94. James EH, Edwards AM, Wigneshweraraj S. 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 [View Article] [PubMed]
     [Google Scholar]
  95. Strobel M, Pförtner H, Tuchscherr L, Völker U, Schmidt F et al. Post-invasion events after infection with Staphylococcus aureus are strongly dependent on both the host cell type and the infecting S. aureus strain. Clin Microbiol Infect 2016; 22:799–809 [View Article] [PubMed]
     [Google Scholar]
  96. Carnes EC, Lopez DM, Donegan NP, Cheung A, Gresham H et al. Confinement-induced quorum sensing of individual Staphylococcus aureus bacteria. Nat Chem Biol 2010; 6:41–45 [View Article] [PubMed]
     [Google Scholar]
  97. Traber KE, Lee E, Benson S, Corrigan R, Cantera M et al. agr function in clinical Staphylococcus aureus isolates. Microbiology 2008; 154:2265–2274 [View Article] [PubMed]
     [Google Scholar]
  98. Shopsin B, Drlica-Wagner A, Mathema B, Adhikari RP, Kreiswirth BN et al. Prevalence of agr dysfunction among colonizing Staphylococcus aureus strains. J Infect Dis 2008; 198:1171–1174 [View Article] [PubMed]
     [Google Scholar]
  99. Shopsin B, Eaton C, Wasserman GA, Mathema B, Adhikari RP et al. Mutations in agr do not persist in natural populations of methicillin-resistant Staphylococcus aureus. J Infect Dis 2010; 202:1593–1599 [View Article] [PubMed]
     [Google Scholar]
  100. Painter KL, Krishna A, Wigneshweraraj S, Edwards AM. What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?. Trends Microbiol 2014; 22:676–685 [View Article] [PubMed]
     [Google Scholar]
  101. Young BC, Wu C-H, Gordon NC, Cole K, Price JR et al. Severe infections emerge from commensal bacteria by adaptive evolution. Elife 2017; 6:e30637 [View Article] [PubMed]
     [Google Scholar]
  102. Lee SO, Lee S, Lee JE, Song K-H, Kang CK et al. Dysfunctional accessory gene regulator (agr) as a prognostic factor in invasive Staphylococcus aureus infection: a systematic review and meta-analysis. Sci Rep 2020; 10:10:20697 [View Article] [PubMed]
     [Google Scholar]
  103. Lee JE, Lee S, Park S, Lee SO, Lee SH. Impact of agr Functionality on the outcome of patients with methicillin-susceptible Staphylococcus aureus bacteremia. Microbiol Spectr 2021; 9:e0011621 [View Article] [PubMed]
     [Google Scholar]
  104. Pader V, Hakim S, Painter KL, Wigneshweraraj S, Clarke TB et al. Staphylococcus aureus inactivates daptomycin by releasing membrane phospholipids. Nat Microbiol 2016; 2:16194 [View Article] [PubMed]
     [Google Scholar]
  105. Altman DR, Sullivan MJ, Chacko KI, Balasubramanian D, Pak TR et al. Genome Plasticity of agr-Defective Staphylococcus aureus during clinical infection. Infect Immun 2018; 86:e00331-18 [View Article] [PubMed]
     [Google Scholar]
  106. Thänert R, Goldmann O, Beineke A, Medina E. Host-inherent variability influences the transcriptional response of Staphylococcus aureus during in vivo infection. Nat Commun 2017; 8:14268 [View Article] [PubMed]
     [Google Scholar]
  107. Siegmund A, Afzal MA, Tetzlaff F, Keinhörster D, Gratani F et al. Intracellular persistence of Staphylococcus aureus in endothelial cells is promoted by the absence of phenol soluble modulins. Virulence 2021; 12:1186–1198 [View Article] [PubMed]
     [Google Scholar]
  108. Proctor R, Fischetti VA, Novick RP, Ferretti JJ, Portnoy DA et al. Respiration and small colony variants of Staphylococcus aureus. Microbiol Spectr 2019; 7: [View Article] [PubMed]
     [Google Scholar]
  109. Tuchscherr L, Löffler B, Proctor RA. Persistence of Staphylococcus aureus: multiple metabolic pathways impact the expression of virulence factors in small-colony variants (SCVs). Front Microbiol 2020; 11:1028 [View Article] [PubMed]
     [Google Scholar]
  110. Gor V, Takemura AJ, Nishitani M, Higashide M, Medrano Romero V et al. Finding of Agr phase variants in Staphylococcus aureus. mBio 2019; 10:e00796-19 [View Article] [PubMed]
     [Google Scholar]
  111. Pollitt EJ, West SA, Crusz SA, Burton-Chellew MN, Hamushan SP. Cooperation, quorum sensing, and evolution of virulence in Staphylococcus aureus. Infect Immun 2014; 82:1045–1051 [View Article] [PubMed]
     [Google Scholar]
  112. He L, Zhang F, Jian Y, Lv H, Hamushan M et al. Key role of quorum-sensing mutations in the development of Staphylococcus aureus clinical device-associated infection. Clin Transl Med 2022; 12:e801 [View Article] [PubMed]
     [Google Scholar]
  113. Laabei M, Peacock SJ, Blane B, Baines SL, Howden BP et al. Significant variability exists in the cytotoxicity of global methicillin-resistant Staphylococcus aureus lineages. Microbiology 2021; 167:001119 [View Article] [PubMed]
     [Google Scholar]
  114. Smyth DS, Kafer JM, Wasserman GA, Velickovic L, Mathema B et al. Nasal carriage as a source of agr-defective Staphylococcus aureus bacteremia. J Infect Dis 2012; 206:1168–1177 [View Article] [PubMed]
     [Google Scholar]
  115. 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 delta- and alpha haemolysins. Mol Microbiol 2006; 59:1519–1530 [View Article] [PubMed]
     [Google Scholar]
  116. Mairpady Shambat S, Siemens N, Monk IR, Mohan DB, Mukundan S et al. A point mutation in AgrC determines cytotoxic or colonizing properties associated with phenotypic variants of ST22 MRSA strains. Sci Rep 2016; 6:31360 [View Article] [PubMed]
     [Google Scholar]
  117. Fleming V, Feil E, Sewell A, Day N, Buckling A et al. Agr interference between clinical Staphylococcus aureus strains in an insect model of virulence. J Bacteriol 2006; 188:7686–7688 [View Article] [PubMed]
     [Google Scholar]
  118. Goerke C, Kümmel M, Dietz K, Wolz C. Evaluation of intraspecies interference due to agr polymorphism in Staphylococcus aureus during infection and colonization. J Infect Dis 2003; 188:250–256 [View Article]
     [Google Scholar]
  119. Goerke C, Campana S, Bayer MG, Döring G, Botzenhart K 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 [View Article] [PubMed]
     [Google Scholar]
  120. Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol 2018; 16:143–155 [View Article] [PubMed]
     [Google Scholar]
  121. Becker K, Heilmann C, Peters G. Coagulase-negative Staphylococci. Clin Microbiol Rev 2014; 27:870–926 [View Article] [PubMed]
     [Google Scholar]
  122. Nakatsuji T, Chen TH, Narala S, Chun KA, Two AM et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci Transl Med 2017; 9:eaah4680 [View Article] [PubMed]
     [Google Scholar]
  123. Brown MM, Horswill AR. Staphylococcus epidermidis - Skin friend or foe?. PLoS Pathog 2020; 16:e1009026 [View Article] [PubMed]
     [Google Scholar]
  124. Severn MM, Horswill AR. Staphylococcus epidermidis and its dual lifestyle in skin health and infection. Nat Rev Microbiol 2023; 21:97–111 [View Article] [PubMed]
     [Google Scholar]
  125. Zhou W, Spoto M, Hardy R, Guan C, Fleming E et al. Host-specific evolutionary and transmission dynamics shape the functional diversification of Staphylococcus epidermidis in human skin. Cell 2020; 180:454–470 [View Article] [PubMed]
     [Google Scholar]
  126. Dufour P, Jarraud S, Vandenesch F, Greenland T, Novick RP et al. High genetic variability of the agr locus in Staphylococcus species. J Bacteriol 2022; 184:1180–1186 [View Article] [PubMed]
     [Google Scholar]
  127. Williams MR, Costa SK, Zaramela LS, Khalil S, Todd DA et al. Quorum sensing between bacterial species on the skin protects against epidermal injury in atopic dermatitis. Sci Transl Med 2019; 11:eaat8329 [View Article] [PubMed]
     [Google Scholar]
  128. Severn MM, Williams MR, Shahbandi A, Bunch ZL, Lyon LM et al. The ubiquitous human skin commensal Staphylococcus hominis protects against opportunistic pathogens. mBio 2022; 13:e0093022 [View Article] [PubMed]
     [Google Scholar]
  129. Olson ME, Todd DA, Schaeffer CR, Paharik AE, Van Dyke MJ et al. Staphylococcus epidermidis agr quorum-sensing system: signal identification, cross talk, and importance in colonization. J Bacteriol 2014; 196:3482–3493 [View Article] [PubMed]
     [Google Scholar]
  130. Ji G, Pei W, Zhang L, Qiu R, Lin J et al. Staphylococcus intermedius produces a functional agr autoinducing peptide containing a cyclic lactone. J Bacteriol 2005; 187:3139–3150 [View Article] [PubMed]
     [Google Scholar]
  131. Chin D, Flannagan RS, Tuffs SW, Chan JK, McCormick JK et al. Staphylococcus lugdunensis uses the agr regulatory system to resist killing by host innate immune effectors. Infect Immun 2022; 90:e0009922 [View Article] [PubMed]
     [Google Scholar]
  132. Otto M, Echner H, Voelter W, Götz F. Pheromone cross-inhibition between Staphylococcus aureus and Staphylococcus epidermidis. Infect Immun 2001; 69:1957–1960 [View Article] [PubMed]
     [Google Scholar]
  133. Yang T, Tal-Gan Y, Paharik AE, Horswill AR, Blackwell HE. Structure-function analyses of a Staphylococcus epidermidis autoinducing peptide reveals motifs critical for AgrC type receptor modulation. ACS Chem Biol 2016; 11:1982–1991 [View Article] [PubMed]
     [Google Scholar]
  134. Brown MM, Kwiecinski JM, Cruz LM, Shahbandi A, Todd DA et al. Novel peptide from commensal Staphylococcus simulans blocks methicillin-resistant Staphylococcus aureus quorum sensing and protects host skin from damage. Antimicrob Agents Chemother 2020; 64:e00172-20 [View Article] [PubMed]
     [Google Scholar]
  135. Paharik AE, Parlet CP, Chung N, Todd DA, Rodriguez EI et al. Coagulase-negative Staphylococcal strain prevents Staphylococcus aureus colonization and skin infection by blocking quorum sensing. Cell Host Microbe 2017; 22:746–756 [View Article] [PubMed]
     [Google Scholar]
  136. Severn MM, Cho Y-SK, Manzer HS, Bunch ZL, Shahbandi A et al. The commensal Staphylococcus warneri makes peptide inhibitors of MRSA quorum sensing that protect skin from atopic or necrotic damage. J Invest Dermatol 2022; 142:3349–3352 [View Article] [PubMed]
     [Google Scholar]
  137. Liu H, Archer NK, Dillen CA, Wang Y, Ashbaugh AG et al. Staphylococcus aureus epicutaneous exposure drives skin inflammation via IL-36-mediated T cell responses. Cell Host Microbe 2021; 147:955–966 [View Article] [PubMed]
     [Google Scholar]
  138. Geoghegan JA, Irvine AD, Foster TJ. Staphylococcus aureus and atopic dermatitis: a complex and evolving relationship. Trends Microbiol 2018; 26:484–497 [View Article] [PubMed]
     [Google Scholar]
  139. Cau L, Williams MR, Butcher AM, Nakatsuji T, Kavanaugh JS et al. Staphylococcus epidermidis protease EcpA can be a deleterious component of the skin microbiome in atopic dermatitis. J Allergy Clin Immunol 2021; 147:955–966 [View Article] [PubMed]
     [Google Scholar]
  140. Ramsey MM, Freire MO, Gabrilska RA, Rumbaugh KP, Lemon KP. Staphylococcus aureus shifts toward commensalism in response to Corynebacterium Species. Front Microbiol 2016; 7:1230 [View Article] [PubMed]
     [Google Scholar]
  141. Nakatsuji T, Hata TR, Tong Y, Cheng YJ, Shafiq F et al. Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial. Nat Med 2021; 27:700–709 [View Article] [PubMed]
     [Google Scholar]
  142. Thoendel M, Kavanaugh JS, Flack CE, Horswill AR. Peptide signaling in the Staphylococci. Chem Rev 2011; 111:117–151 [View Article] [PubMed]
     [Google Scholar]
  143. Zhang Y. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics 2008; 9:40 [View Article] [PubMed]
     [Google Scholar]
  144. Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E et al. Scalable molecular dynamics with NAMD. J Comput Chem 2005; 26:1781–1802 [View Article] [PubMed]
     [Google Scholar]
  145. Jo S, Kim T, Iyer VG, Im W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J Comput Chem 2008; 29:1859–1865 [View Article] [PubMed]
     [Google Scholar]
  146. Buel GR, Walters KJ. Can AlphaFold2 predict the impact of missense mutations on structure?. Nat Struct Mol Biol 2022; 29:1–2 [View Article] [PubMed]
     [Google Scholar]
  147. Kozakov D, Hall DR, Xia B, Porter KA, Padhorny D et al. The ClusPro web server for protein-protein docking. Nat Protoc 2017; 12:255–278 [View Article] [PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.001381
Loading
Quorum-sensing, intra- and inter-species competition in the staphylococci
Microbiology 169, 001381 (2023); https://doi.org/10.1099/mic.0.001381
/content/journal/micro/10.1099/mic.0.001381
/content/journal/micro/10.1099/mic.0.001381
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error