Virulence factors produced by staphylococcus aureus biofilms have a moonlighting function contributing to biofilm integrity

Molecular and Cellular Proteomics

Volumn 18, Issue 6, 2019, Pages 1036-1053

  Graf, Alexander C ^a   Leonard, Anne ^a   Schäuble, Manuel ^a   Rieckmann, Lisa M ^a   Hoyer, Juliane ^a   Maass, Sandra ^a   Lalk, Michael ^a   Becher, Dörte ^a   Pané Farré, Jan ^a   Riedel, Katharina ^a  

^a UNIVERSITY OF GREIFSWALD   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL PROTEIN; HEMOLYSIN; PROTEOME; RIBOSOME PROTEIN; TRIACYLGLYCEROL LIPASE; VIRULENCE FACTOR; ACID; BACTERIAL DNA; OXYGEN;

ACIDIFICATION; ARTICLE; BACTERIAL CELL; BACTERIAL VIRULENCE; BACTERIUM CULTURE; BIOFILM; CELL AGGREGATION; CELL SURFACE; CELLULAR DISTRIBUTION; CONTROLLED STUDY; EXTRACELLULAR MATRIX; GALLERIA MELLONELLA; HEMOLYSIS ASSAY; HOST BACTERIUM INTERACTION; NONHUMAN; OSMOTIC STRESS; PH; PRIORITY JOURNAL; STAPHYLOCOCCUS AUREUS; STATIC ELECTRICITY; ANIMAL; BIOLOGICAL MODEL; CYTOLOGY; DRUG EFFECT; LEPORIDAE; METABOLISM; METABOLOME; MICROBIOLOGY; MOTH; OSMOTIC PRESSURE; PHENOTYPE; PHYSIOLOGY; PLANKTON;

ACIDS; ANIMALS; BACTERIAL PROTEINS; BIOFILMS; DNA, BACTERIAL; EXTRACELLULAR MATRIX; METABOLOME; MODELS, BIOLOGICAL; MOTHS; OSMOTIC PRESSURE; OXYGEN; PHENOTYPE; PLANKTON; RABBITS; RIBOSOMAL PROTEINS; STAPHYLOCOCCUS AUREUS; VIRULENCE FACTORS;

EID: 85066483399     PISSN: 15359476     EISSN: 15359484     Source Type: Journal    
DOI: 10.1074/mcp.RA118.001120     Document Type: Article

References (120)

1. Costerton, J. W., Geesey, G. G., and Cheng, K. J. (1978) How bacteria stick. Sci. Am. 238, 2–11
2. Donlan, R. M. (2002) Biofilms: microbial life on surfaces. Emerg. Infect. Dis. 8, 881–890
3. Flemming, H. C., and Wingender, J. (2010) The biofilm matrix. Nat. Rev. Microbiol. 8, 1–11
4. Otto, M. (2008) Staphylococcal biofilms. Curr. Top. Microbiol. Immunol. 322, 207–228
5. Stewart, P. S., and William Costerton, J. (2001) Antibiotic resistance of bacteria in biofilms. Lancet 358, 135–138
6. Joo, H. S., and Otto, M. (2012) Molecular basis of in vivo biofilm formation by bacterial pathogens. Chem. Biol. 19, 1503–1513
7. Römling, U., and Balsalobre, C. (2012) Biofilm infections, their resilience to therapy and innovative treatment strategies. J. Int. Med. 272, 541–561
8. Lister, J. L., and Horswill, A. R. (2014) Staphylococcus aureus biofilms: recent developments in biofilm dispersal. Front Cell Infect Microbiol. 4, 1–9
9. Chatterjee, S., Maiti, P., Dey, R., Kundu, A., and Dey, R. (2014) Biofilms on indwelling urologic devices: microbes and antimicrobial management prospect. Ann. Med. Health Sci. Res. 4, 100–104
10. Kiedrowski, M. R., and Horswill, A. R. (2011) New approaches for treating staphylococcal biofilm infections. Ann. N.Y. Acad. Sci. 1241, 104–121
11. Barrett, L., and Atkins, B. (2014) The clinical presentation of prosthetic joint infection. J. Antimicrob. Chemother. 69, i25-i27
12. Parsek, M. R., and Singh, P. K. (2003) Bacterial biofilms: an emerging link to disease pathogenesis. Annu. Rev. Microbiol. 57, 677–701
13. O’Toole, G. A., Kaplan, H. B., and Kolter, R. (2000) Biofilm formation as microbial development. Annu. Rev. Microbiol. 54, 1–37
14. Moormeier, D. E., Bose, J. L., Horswill, A. R., and Bayles, K. W. (2014) Temporal and stochastic control of Staphylococcus aureus biofilm development 5, e01341-14
15. Speziale, P., Pietrocola, G., Foster, T. J., and Geoghegan, J. A. (2014) Protein-based biofilm matrices in Staphylococci. Front Cell Infect Microbiol. 4, 1–10
16. Payne, D. E., and Boles, B. R. (2016) Emerging interactions between matrix components during biofilm development. Curr. Genet. 62, 137–141
17. Paharik, A. E., and Horswill, A. R. (2016) The Staphylococcal biofilm: adhesins, regulation, and host response. Microbiol. Spectr. 4, 1–48
18. Moche, M., Schlüter, R., Bernhardt, J., Plate, K., Riedel, K., Hecker, M., and Becher, D. (2015) Time-resolved analysis of cytosolic and surface-associated proteins of Staphylococcus aureusHG001 under planktonic and biofilm conditions. J. Proteome Res. 14, 3804–3822
19. Ammons, M. C. B., Tripet, B. P., Carlson, R. P., Kirker, K. R., Gross, M. A., Stanisich, J. J., and Copié, V. (2014) Quantitative NMR Metabolite Profiling of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureusDiscriminates between Biofilm and Planktonic Phenotypes. J. Proteome Res. 13, 2973–2985
20. Atshan, S. S., Shamsudin, M. N., Sekawi, Z., Thian Lung, L. T., Barantalab, F., Liew, Y. K., Alreshidi, M. A., Abduljaleel, S. A., and Hamat, R. A. (2015) Comparative proteomic analysis of extracellular proteins expressed by various clonal types of Staphylococcus aureus and during planktonic growth and biofilm development. Front. Microbiol. 6, 1081–1089
21. Beenken, K. E., Dunman, P. M., McAleese, F., Macapagal, D., Murphy, E., Projan, S. J., Blevins, J. S., Smeltzer, M. S. (2004) Global gene expression in Staphylococcus aureus biofilms. J. Bacteriol. 186, 4665–4684
22. Bénard, L., Litzler, P. Y., Cosette, P., Lemeland, J. F., Jouenne, T., and Junter, G. A. (2009) Proteomic analysis of Staphylococcus aureus biofilms grown in vitroon mechanical heart valve leaflets. J. Biomed. Mater. Res. 88, 1069 –1078
23. Islam, N., Ross, J. M., and Marten, M. R. (2015) Proteome analyses of Staphylococcus aureus biofilm at elevated levels of NaCl. Clin. Microbiol. 4, 1–15
24. Junka, A. F., Deja, S., Smutnicka, D., Szymczyk, P., Ziółkowski, G., Bartoszewicz, M., and Młynarz, P. (2013) Differences in metabolic profiles of planktonic and biofilm cells in Staphylococcus aureus - (1)H Nuclear Magnetic Resonance search for candidate biomarkers. Acta Biochim. Pol. 60, 701–706
25. Resch, A., Leicht, S., Saric, M., Pásztor, L., Jakob, A., Götz, F., Nordheim, A. (2006) Comparative proteome analysis of S. aureus biofilm and planktonic cells and correlation with transcriptome profiling. Proteomics 6, 1867–1877
26. Resch, A., Rosenstein, R., Nerz, C., and Götz, F. (2005) Differential gene expression profiling of Staphylococcus aureus cultivated under biofilm and planktonic conditions. Appl. Environ. Microbiol. 71, 2663–2676
27. Tan, X., Qin, N., Wu, C., Sheng, J., Yang, R., Zheng, B., Ma, Z., Liu, L., Peng, X., and Jia, A. (2015) Transcriptome analysis of the biofilm formed by methicillin-susceptible Staphylococcus aureus. Sci. Rep. 5, 1–12
28. Seper, A., Pressler, K., Kariisa, A., Haid, A. G., Roier, S., Leitner, D. R., Reidl, J., Tamayo, R., and Schild, S. (2014) Identification of genes induced in Vibrio cholerae in a dynamic biofilm system. Int. J. Med. Microbiol. 304, 749–763
29. Herbert, S., Ziebandt, A. K., Ohlsen, K., Schäfer, T., Hecker, M., Albrecht, D., Novick, R., and Götz, F. (2010) Repair of global regulators in Staphylococcus aureus 8325 and comparative analysis with other clinical isolates. Infection Immunity 78, 2877–2889
30. Gertz, S., Engelmann, S., Schmid, R., Ohlsen, K., Hacker, J., and Hecker, M. (1999) Regulation of SigmaB-dependent transcription of sigB and asp23 in two different S. aureus strains. Mol Gen Genet. 61, 558–566
31. Dörries, K., and Lalk, M. (2013) Metabolic footprint analysis uncovers strain specific overflow metabolism and D-isoleucine production of Staphylococcus Aureus COL and HG001. PLOS ONE 8, e81500-9
32. Dohnt, K., Sauer, M., Müller, M., Atallah, K., Weidemann, M., Gronemeyer, P., Rasch, D., Tielen, P., and Krull, R. (2011) An in vitro urinary tract catheter system to investigate biofilm development in catheter-associated urinary tract infections. J. Microbiol. Methods 87, 302–308
33. Brady, R. A., Leid, J. G., Camper, A. K., Costerton, J. W., and Shirtliff, M. E. (2006) Identification of Staphylococcus aureus proteins recognized by the antibody-mediated immune response to a biofilm infection. Infection Immunity 74, 3415–3426
34. Toyofuku, M., Roschitzki, B., Riedel, K., and Eberl, L. (2012) Identification of proteins associated with the Pseudomonas aeruginosa biofilm extracellular matrix. J. Proteome Res. 11, 4906–4915
35. Rice, K. C., Mann, E. E., Endres, J. L., Weiss, E. C., Cassat, J. E., Smeltzer, M. S., and Bayles, K. W. (2007) The cidA murein hydrolase regulator contributes to DNA release and biofilm development in Staphylococcus aureus. Proc. Natl. Acad. Sci. U.S.A. 104, 8113– 8118
36. Bose, J. L., Lehman, M. K., Fey, P. D., and Bayles, K. W. (2012) Contribution of the Staphylococcus aureus Atl AM and GL murein hydrolase activities in cell division, autolysis, and biofilm formation. PLOS ONE 7, e42244-11
37. Becher, D., Hempel, K., Sievers, S., Zühlke, D., Pané-Farré, J., Otto, A., Fuchs, S., Albrecht, D., Bernhardt, J., Engelmann, S., Völker, U., van Dijl, J. M., and Hecker, M. (2009) A proteomic view of an important human pathogen - towards the quantification of the entire Staphylococcus aureus proteome. PLOS ONE 4, e8176-12
38. Zühlke, D., Dörries, K., Bernhardt, J., Maa, S., Muntel, J., Liebscher, V., Pané-Farré, J., Riedel, K., Lalk, M., Völker, U., Engelmann, S., Becher, D., Fuchs, S., and Hecker, M. (2016) Costs of life - Dynamics of the protein inventory of Staphylococcus aureus during anaerobiosis. Sci. Rep. 6, 1–13
39. Bonn, F., Bartel, J., Büttner, K., Hecker, M., Otto, A., and Becher, D. (2014) Picking vanished proteins from the void: how to collect and ship/share extremely dilute proteins in a reproducible and highly efficient manner. Anal. Chem. 86, 7421–7427
40. Bradford, M. M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254
41. Smith, P. K., Krohn, R. I., Hermanson, G. T., and Mallia, A. K. (1985) Measurement of protein using bicinchoninic acid. Anal. Biochem. 150, 76–85
42. Laemmli, U. K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685
43. Neuhoff, V., Arold, N., Taube, D., and Ehrhardt, W. (1988) Improved staining of proteins in polyacrylamide gels including isoelectric focusing gels with clear background at nanogram sensitivity using Coomassie Brilliant Blue G-250 and R-250. Electrophoresis 9, 255–262
44. Cox, J., and Mann, M. (2008) MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367–1372
45. Cox, J., Neuhauser, N., Michalski, A., Scheltema, R. A., Olsen, J. V., and Mann, M. (2011) Andromeda: a peptide search engine integrated into the MaxQuant environment. J. Proteome Res. 10, 1794–1805
46. Cox, J., Hein, M.Y., Luber, C.A., Paron, I., Nagaraj, N., and Mann, M. (2014) Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ. Mol. Cell. Proteomics 13, 2513–2526
47. Tyanova, S., Temu, T., and Cox, J. (2016) The MaxQuant computational platform for mass spectrometry-based shotgun proteomics. Nat. Protocols 11, 2301–2319
48. Bernhardt, J., Funke, S., Hecker, M., and Siebourg, J. Visualizing gene expression data via Voronoi treemaps. 2009 Sixth International Symposium on Voronoi Diagrams, pp. 233–241, Copenhagen
49. Liebermeister, W., Noor, E., Flamholz, A., Davidi, D., Bernhardt, J., and Milo, R. (2014) Visual account of protein investment in cellular functions. Proc. Natl. Acad. Sci. U.S.A. 111, 8488 – 8493
50. Overbeek, R. (2005) The subsystems approach to genome annotation and its use in the project to annotate 1000 genomes. Nucleic Acids Res. 33, 5691–5702
51. Otto, A., Bernhardt, J. O. R., Meyer, H., Schaffer, M., Herbst, F. A., Siebourg, J., Mader, U., Lalk, M., Hecker, M., and Becher, D. 2010. Systems-wide temporal proteomic profiling in glucose-starved Bacillus subtilis. Nat. Communications 1, 137–139
52. Yu, N. Y., Wagner, J. R., Laird, M. R., Melli, G., Rey, S., Lo, R., Dao, P., Sahinalp, S. C., Ester, M., Foster, L. J., Brinkman, F. S. L. (2010) PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all pro-karyotes. Bioinformatics 26, 1608–1615
53. Fuchs, S., Mehlan, H., Bernhardt, J., Hennig, A., Michalik, S., Surmann, K., Pané-Farré, J., Giese, A., Weiss, S., Backert, L., Herbig, A., Nieselt, K., Hecker, M., Völker, U., and Mäder, U. (2017) AureoWiki - The repository of the Staphylococcus aureus research and annotation community. Int. J. Med. Microbiol. 308, 558 –568
54. Zhou, M., Boekhorst, J., Francke, C., and Siezen, R. J. (2008) LocateP: Genome-scale subcellular-location predictor for bacterial proteins. BMC Bioinformatics 9, 173–117
55. Petersen, T. N., Brunak, S., Heijne von, G., and Nielsen, H. (2011) SignalP 4.0: discriminating signal peptides from transmembrane regions. Nat. Rev. Microbiol. 8, 785–786
56. Sternberg, C., and Tolker-Nielsen, T. (2006) Growing and analyzing biofilms in flow cells. Curr. Protoc. Microbiol. Chapter 1:Unit 1B.2–1B.2.15
57. Seidl, K., Goerke, C., Wolz, C., Mack, D., Berger-Bachi, B., and Bischoff, M. (2008) Staphylococcus aureus CcpA affects biofilm formation. infection and immunity. Infect. Immun. 76, 2044–2050
58. Hill, L., Veli, N., and Coote, P.J. (2014) Evaluation of Galleria mellonella larvae for measuring the efficacy and pharmacokinetics of antibiotic therapies against Pseudomonas aeruginosa infection. Int. J. Antimicrobial Agents 43, 254–261
59. Lauderdale, K. J., Boles, B. R., Cheung, A. L., and Horswill, A. R. (2009) Interconnections between Sigma B, agr, and proteolytic activity in Staphylococcus aureus biofilm maturation. Infection Immunity 77, 1623–1635
60. Stoodley, P., Sauer, K., Davies, D. G., and Costerton, J. W. (2002) Biofilms as complex differentiated communities. Annu. Rev. Microbiol. 56, 187–209
61. Spoering, A. L., and Lewis, K. (2001) Biofilms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimi-crobials. J. Bacteriol. 183, 6746–6751
62. Waite, R. D., Papakonstantinopoulou, A., Littler, E., and Curtis, M. A. (2005) Transcriptome analysis of Pseudomonas aeruginosa growth: comparison of gene expression in planktonic cultures and developing and mature biofilms. J. Bacteriol. 187, 6571–6576
63. Folsom, J. P., Richards, L., Pitts, B., Roe, F., Ehrlich, G. D., Parker, A., Mazurie, A., and Stewart, P. S. (2010) Physiology of Pseudomonas aeruginosa in biofilms as revealed by transcriptome analysis. BMC Microbiol. 10, 294
64. Boles, B. R., and Horswill, A. R. (2008) agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog. 4, e1000052-13
65. Egeter, O., and Bruckner, R. (1996) Catabolite repression mediated by the catabolite control protein CcpA in Staphylococcus xylosus. Mol. Microbiol. 21, 739–749
66. Geiger, T., and Wolz, C. (2014) Intersection of the stringent response and the CodY regulon in low GC Gram-positive bacteria. Int. J. Med. Microbiol. 304, 150–155
67. Soutourina, O., Poupel, O., Coppée, J. Y., Danchin, A., Msadek, T., and Martin-Verstraete, I. (2009) CymR, the master regulator of cysteine metabolism in Staphylococcus aureus, controls host sulphur source utilization and plays a role in biofilm formation. Mol. Microbiol. 73, 194–211
68. Prigent-Combaret, C., Vidal, O., Dorel, C., and Lejeune, P. (1999) Abiotic surface sensing and biofilm-dependent regulation of gene expression in Escherichia coli. J. Bacteriol. 181, 5993–6002
69. Borriello, G., Werner, E., Roe, F., Kim, A. M., Ehrlich, G. D., and Stewart, P. S. (2004) Oxygen limitation contributes to antibiotic tolerance of Pseudomonas aeruginosa in biofilms. Antimicrobial Agents Chemother. 48, 2659 –2664
70. Sønderholm, M., Bjarnsholt, T., Alhede, M., Kolpen, M., Jensen, P., Kühl, M., and Kragh, K. (2017) The consequences of being in an infectious biofilm: microenvironmental conditions governing antibiotic tolerance. IJMS 18, 2688–2614
71. Kinkel, T. L., Roux, C. M., Dunman, P. M., and Fang, F. C. (2013) The Staphylococcus aureus SrrAB two-component system promotes resistance to nitrosative stress and hypoxia. mBio 4, e00696-13
72. Foulston, L., Elsholz, A. K. W., DeFrancesco, A. S., and Losick, R. (2014) The extracellular matrix of Staphylococcus aureus biofilms comprises cytoplasmic proteins that associate with the cell surface in response to decreasing pH. Mbio 5, e01667-14
73. Dengler, V., Foulston, L., DeFrancesco, A. S., and Losick, R. (2015) An electrostatic net model for the role of extracellular DNA in biofilm formation by Staphylococcus aureus. J. Bacteriol. 197, 3779–3787
74. Xu, Y., Maltesen, R. G., Larsen, L. H., Schønheyder, H. C., Le, V. Q., Nielsen, J. L., Nielsen, P. H., Thomsen, T. R., and Nielsen, K. L. (2016) In vivo gene expression in a Staphylococcus aureus prosthetic joint infection characterized by RNA sequencing and metabolomics: a pilot study. BMC Microbiol. 16, 1–12
75. Li, Y. H., Chen, Y. Y. M., and Burne, R. A. (2000) Regulation of urease gene expression by Streptococcus salivarius growing in biofilms. Environmental Microbiol. 2, 169 –177
76. Lassek, C., Burghartz, M., Chaves-Moreno, D., Otto, A., Hentschker, C., Fuchs, S., Bernhardt, J., Jauregui, R., Neubauer, R., Becher, D., Pieper, D. H., Jahn, M., Jahn, D., and Riedel, K. (2015) A metaproteomics approach to elucidate host and pathogen protein expression during catheter-associated urinary tract infections (CAUTIs). Mol. Cell. Proteomics 14, 989–1008
77. Ebner, P., Prax, M., Nega, M., Koch, I., Dube, L., Yu, W., Rinker, J., Popella, P., Flötenmeyer, M., and Götz, F. (2015) Excretion of cytoplasmic proteins (ECP) in Staphylococcus aureus. Mol. Microbiol. 97, 775–789
78. Ebner, P., Rinker, J., Nguyen, M. T., Popella, P., Nega, M., Luqman, A., Schittek, B., Di Marco, M., Stevanovic, S., and Götz, F. (2016) Excreted cytoplasmic proteins contribute to pathogenicity in Staphylococcus aureus. Infection Immunity 84, 1672–1681
79. Houston, P., Rowe, S. E., Pozzi, C., Waters, E. M., and O’Gara, J.P. (2011) Essential role for the major autolysin in the fibronectin-binding protein-mediated Staphylococcus aureus biofilm phenotype. Infection Immunity 79, 1153–1165
80. Mashruwala, A.A., van de Guchte, A., and Boyd, J.M. (2017) Impaired respiration elicits SrrAB-dependent programmed cell lysis and biofilm formation in Staphylococcus aureus. eLife 6, e23845
81. Pásztor, L., Ziebandt, A. K., Nega, M., Schlag, M., Haase, S., Franz-Wachtel, M., Madlung, J., Nordheim, A., Heinrichs, D. E., and Götz, F. (2010) Staphylococcal major autolysin (Atl) is involved in excretion of cytoplasmic proteins. J. Biol. Chem. 285, 36794–36803
82. Dinges, M. M., Orwin, P. M., and Schlievert, P. M. (2000) Exotoxins of Staphylococcus aureus. Clin. Microbiol. Rev. 13, 16–34
83. Peschel, A., and Otto, M. (2013) Phenol-soluble modulins and staphylococcal infection. Nat. Rev. Microbiol. 11, 667–673
84. Alonzo, F., and Torres, V. J. (2014) The bicomponent pore-forming leu-cocidins of Staphylococcus aureus. Microbiol. Mol. Biol. Rev. 78, 199–230
85. Nguyen, M. T., Luqman, A., Bitschar, K., Hertlein, T., Dick, J., Ohlsen, K., Bröker, B., Schittek, B., and Götz, F. (2017) Staphylococcal (phos-pho)lipases promote biofilm formation and host cell invasion. Int. J. Med. Microbio. 308, 1–11
86. Scherr, T. D., Hanke, M. L., Huang, O., James, D. B. A., Horswill, A. R., Bayles, K. W., Fey, P. D., Torres, V. J., and Kielian, T. (2015) Staphylococcus aureus biofilms induce macrophage dysfunction through leuko-cidin AB and alpha-toxin. mBio 6, e01021-15-13
87. Reijer den, P. M., Haisma, E. M., Lemmens-den Toom, N. A., Willemse, J., Koning, R. A., Demmers, J. A. A., Dekkers, D. H. W., Rijkers, E., Ghalbzouri El, A., Nibbering, P. H., and van Wamel, W. (2016) Detection of alpha-toxin and other virulence factors in biofilms of Staphylococcus aureus on polystyrene and a human epidermal model. PLOS ONE 11, e0152544
88. Lei, M. G., Gupta, R. K., and Lee, C. Y. (2017) Proteomics of Staphylococcus aureus biofilm matrix in a rat model of orthopedic implant-associated infection. PLOS ONE 12, e0187981
89. Bayer, M. G., Heinrichs, J. H., and Cheung, A. L. (1996) The molecular architecture of the sar locus in Staphylococcus aureus. J. Bacteriol. 178, 4563–4570
90. Sonohara, R., Muramatsu, N., Ohshima, H., and Kondo, T. (1995) Difference in surface-properties between Escherichia-coli and Staphylococcus-aureus as revealed by electrophoretic mobility measurements. Bio-phys. Chem. 55, 273–277
91. Nostro, A., Cellini, L., Di Giulio, M., D’Arrigo, M., Marino, A., Blanco, A. R., Favaloro, A., Cutroneo, G., and Bisignano, G. (2012) Effect of alkaline pH on staphylococcal biofilm formation. APMIS 120, 733–742
92. Jennings, L. K., Storek, K. M., Ledvina, H. E., Coulon, C., Marmont, L. S., Sadovskaya, I., Secor, P. R., Tseng, B. S., Scian, M., Filloux, A., Wozniak, D. J., Howell, P. L., and Parsek, M. R. (2015) Pel is a cationic exopolysaccharide that cross-links extracellular DNA in the Pseudomonas aeruginosabiofilm matrix. Proc. Natl. Acad. Sci. U.S.A. 112, 11353–11358
93. Beenken, K. E., Blevins, J. S., and Smeltzer, M. S. (2003) Mutation of sarA in Staphylococcus aureus limits biofilm formation. infection and immunity. Infect. Immun. 71, 4206–4211
94. O’Neill, E., Pozzi, C., Houston, P., Smyth, D., Humphreys, H., Robinson, D. A., and O’Gara, J. P. 2007. Association between methicillin susceptibility and biofilm regulation in Staphylococcus aureus isolates from device-related infections. J. Clin. Microbiol. 45, 1379–1388
95. Lauderdale, K. J., Malone, C. L., Boles, B. R., Morcuende, J., and Horswill, A. R. (2009) Biofilm dispersal of community-associated methicillin-resistant Staphylococcus aureuson orthopedic implant material. J. Or-thop. Res. 81, 55– 61
96. Tsang, L. H., Cassat, J. E., Shaw, L. N., Beenken, K. E., and Smeltzer, M. S. (2008) Factors Contributing to the Biofilm-Deficient Phenotype of Staphylococcus aureus sarA Mutants. PLOS ONE 3, e3361
97. O’Neill, E., Pozzi, C., Houston, P., Humphreys, H., Robinson, D. A., Loughman, A., Foster, T. J., and O’Gara, J. P. (2008) A novel Staphylococcus aureus biofilm phenotype mediated by the fibronectin-binding proteins, FnBPA and FnBPB. J. Bacteriol. 190, 3835–3850
98. Boles, B. R., Thoendel, M., Roth, A. J., Horswill, A. R. (2010) Identification of genes involved in polysaccharide-independent Staphylococcus aureus biofilm formation. PLOS ONE 5, e10146
99. Foster, T.J., Geoghegan, J.A., Ganesh, V.K., and Höök, M. (2014) Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat. Rev. Microbiol. 12, 49 – 62
100. Mann, E. E., Rice, K. C., Boles, B. R., Endres, J. L., Ranjit, D., Chandramo-han, L., Tsang, L. H., Smeltzer, M. S., Horswill, A. R., and Bayles, K. W. (2009) Modulation of eDNA release and degradation affects Staphylococcus aureus biofilm maturation. PLOS ONE 4, e5822
101. Peschel, A., Otto, M., Jack, R. W., Kalbacher, H., Jung, G., and Götz, F. (1999) Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J. Biol. Chem. 274, 8405–8410
102. Tsai, M., Ohniwa, R. L., Kato, Y., Takeshita, S. L., Ohta, T., Saito, S., Hayashi, H., and Morikawa, K. (2011) Staphylococcus aureus requires cardiolipin for survival under conditions of high salinity. BMC Microbiol. 11, 13
103. Gries, C. M., Bose, J. L., Nuxoll, A. S., Fey, P. D., and Bayles, K. W. (2013) The Ktr potassium transport system in Staphylococcus aureus and its role in cell physiology, antimicrobial resistance and pathogenesis. Mol. Microbiol. 89, 760–773
104. Price-Whelan, A., Poon, C. K., Benson, M. A., Eidem, T. T., Roux, C. M., Boyd, J. M., Dunman, P. M., Torres, V. J., and Krulwich, T. A. (2013) Transcriptional profiling of Staphylococcus aureus during growth in 2 M NaCl leads to clarification of physiological roles for Kdp and Ktr K uptake systems. MBio 4, e00407
105. Jonsson, P., and Wadström, T. (1984) Cell-surface hydrophobicity of Staphylococcus-aureus measured by the salt aggregation test (Sat). Curr. Microbiol. 10, 203–209
106. Rachid, S., Ohlsen, K., Wallner, U., Hacker, J., Hecker, M., and Ziebuhr, W. (2000) Alternative transcription factor sigma(B) is involved in regulation of biofilm expression in a Staphylococcus aureus mucosal isolate. J. Bacteriol. 182, 6824–6826
107. Seminara, A., Angelini, T. E., Wilking, J. N., Vlamakis, H., Ebrahim, S., Kolter, R., Weitz, D. A., and Brenner, M. P. 2012. Osmotic spreading of Bacillus subtilis biofilms driven by an extracellular matrix. Proc. Natl. Acad. Sci. U.S.A. 109, 1116–1121
108. Yan, J., Nadell, C. D., Stone, H. A., Wingreen, N. S., and Bassler, B. L. (2017) Extracellular-matrix-mediated osmotic pressure drives Vibrio cholerae biofilm expansion and cheater exclusion. Nat. Commun. 8, 1–11
109. Freeman, Z. N., Dorus, S., and Waterfield, N. R. (2013) The KdpD/KdpE two-component system: integrating K homeostasis and virulence. PLoS Pathog. 9, e1003201
110. Xue, T., You, Y., Hong, D., Sun, H., and Sun, B. (2011) The Staphylococcus aureus KdpDE two-component system couples extracellular K sensing and Agr signaling to infection programming. Infection Immunity 79, 2154 –2167
111. Zhao, L., Xue, T., Shang, F., Sun, H., and Sun, B. (2010) Staphylococcus aureus AI-2 quorum sensing associates with the KdpDE two-component system to regulate capsular polysaccharide synthesis and virulence. Infection Immunity 78, 3506–3515
112. Coelho, L. R., Souza, R. R., Ferreira, F. A., Guimaraes, M. A., Ferreira-Carvalho, B. T., and Figueiredo, A. M. S. (2008) agr RNAIII divergently regulates glucose-induced biofilm formation in clinical isolates of Staphylococcus aureus. Microbiology 154, 3480–3490
113. Queck, S. Y., Jameson-Lee, M., Villaruz, A. E., Bach, T. H. L., Khan, B. A., Sturdevant, D. E., Ricklefs, S. M., Li, M., and Otto, M. (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, 150–158
114. Said-Salim, B., Dunman, P. M., McAleese, F. M., Macapagal, D., Murphy, E., McNamara, P. J., Arvidson, S., Foster, T. J., Projan, S. J., and Kreiswirth, B. N. (2003) Global regulation of Staphylococcus aureus genes by Rot. J. Bacteriol. 185, 610–619
115. Majerczyk, C. D., Sadykov, M. R., Luong, T. T., Lee, C., Somerville, G. A., and Sonenshein, A. L. (2008) Staphylococcus aureus CodY negatively regulates virulence gene expression. J. Bacteriol. 190, 2257–2265
116. Mrak, L. N., Zielinska, A. K., Beenken, K. E., Mrak, I. N., Atwood, D. N., Griffin, L. M., Lee, C. Y., and Smeltzer, M. S. (2012) saeRS and sarA act synergistically to repress protease production and promote biofilm formation in Staphylococcus aureus. PLOS ONE 7, e38453
117. Rogasch, K., Ruhmling, V., Pané-Farré, J., Hoper, D., Weinberg, C., Fuchs, S., Schmudde, M., Broker, B.M., Wolz, C., Hecker, M., and Engelmann, S. (2006) Influence of the two-component system SaeRS on global gene expression in two different Staphylococcus aureus strains. J. Bacteriol. 188, 7742–7758
118. Pragman, A. A., Yarwood, J. M., Tripp, T. J., and Schlievert, P. M. (2004) Characterization of virulence factor regulation by SrrAB, a two-component system in Staphylococcus aureus. J. Bacteriol. 186, 2430–2438
119. Fournier, B., and Hooper, D. C. (2000) A new two-component regulatory system involved in adhesion, autolysis, and extracellular proteolytic activity of Staphylococcus aureus. J. Bacteriol. 182, 3955–3964
120. Vizcaíno, A., Côté, R.G., Csordas, A., Dianes, J.A., Fabregat, A., Foster, J.M., Griss, J., Alpi, E., Birim, M., Contell, J., O’Kelly, G., Schoenegger, A., Ovelleiro, D., Pérez-Riverol, Y., Reisinger, F., Ríos, D., Wang, R., and Hermjakob, H. (2012) The proteomics identifications (PRIDE) database and associated tools: status in 2013. Nucleic Acids Res. 41, D1063–D1069