Current Microbiology

, Volume 76, Issue 1, pp 70–77 | Cite as

Role of SigB and Staphyloxanthin in Radiation Survival of Staphylococcus aureus

  • Miri K. Pannu
  • Deborah A. Hudman
  • Neil J. Sargentini
  • Vineet K. SinghEmail author


Staphylococcus aureus is a potent human pathogen. The virulence of this bacterium depends on a multitude of factors that it produces. One such virulence factor is the golden pigment, staphyloxanthin, which has been shown to protect the bacterium from oxidative stress. Expression of the staphyloxanthin biosynthetic pathway is dependent on SigB, a global stress response regulator in S. aureus. This study investigated the role of staphyloxanthin and SigB in protection of S. aureus from radiation damage. Using stationary-phase bacterial cells, it was determined that the staphyloxanthin-deficient (crt mutant) strain was significantly sensitive to UV radiation (~ threefold), but not sensitive to X-radiation. However, a SigB-deficient S. aureus that also lacks staphyloxanthin, was significantly sensitive to both UV- and X-radiation. To confirm that protection from X-radiation was due to hydroxyl radicals, effect of 3 M glycerol, a known hydroxyl scavenger, was also investigated. Glycerol increased the survival of the S. aureus sigB mutant to the wild-type level suggesting that the X-radiation sensitivity of these mutants was due to deficiency in scavenging hydroxyl radicals. In summary, SigB is critical for protection of S. aureus cells from radiation damage.



This study was supported by the Master of Science in Biomedical Sciences program at A.T. Still University of Health Sciences, Kirksville College of Osteopathic Medicine (Grant No. 850-608).


  1. 1.
    Augustin J, Rosenstein R, Wieland B, Schneider U, Schnell N, Engelke G, Entian KD, Gotz F (1992) Genetic analysis of epidermin biosynthetic genes and epidermin-negative mutants of Staphylococcus epidermidis. Eur J Biochem 204:1149–1154CrossRefGoogle Scholar
  2. 2.
    Bischoff M, Dunman P, Kormanec J, Macapagal D, Murphy E, Mounts W, Berger-Bachi B, Projan S (2004) Microarray-based analysis of the Staphylococcus aureus sigmaB regulon. J Bacteriol 186:4085–4099CrossRefGoogle Scholar
  3. 3.
    Cadet J, Ravanat JL, TavernaPorro M, Menoni H, Angelov D (2012) Oxidatively generated complex DNA damage: tandem and clustered lesions. Cancer Lett 327:5–15CrossRefGoogle Scholar
  4. 4.
    Clauditz A, Resch A, Wieland KP, Peschel A, Gotz F (2006) Staphyloxanthin plays a role in the fitness of Staphylococcus aureus and its ability to cope with oxidative stress. Infect Immun 74:4950–4953CrossRefGoogle Scholar
  5. 5.
    Esposito S, Terranova L, Macchini F, Bianchini S, Biffi G, Vigano M, Pelucchi C, Leva E, Principi N (2018) Staphylococcus aureus colonization and risk of surgical site infection in children undergoing clean elective surgery: a cohort study. Medicine (Baltimore) 97:e11097CrossRefGoogle Scholar
  6. 6.
    Ewing D, Walton HL (1991) Do.OH scavenger secondary radicals protect by competing with oxygen for cellular target sites? Radiat Res 128:29–36CrossRefGoogle Scholar
  7. 7.
    Fiedor J, Burda K (2014) Potential role of carotenoids as antioxidants in human health and disease. Nutrients 6:466–488CrossRefGoogle Scholar
  8. 8.
    Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, Ellenberger T (2006) DNA repair and mutagenesis, 2nd edn. ASM Press, Washington DCGoogle Scholar
  9. 9.
    Gertz S, Engelmann S, Schmid R, Ziebandt AK, Tischer K, Scharf C, Hacker J, Hecker M (2000) Characterization of the sigma(B) regulon in Staphylococcus aureus. J Bacteriol 182:6983–6991CrossRefGoogle Scholar
  10. 10.
    Giachino P, Engelmann S, Bischoff M (2001) Sigma(B) activity depends on RsbU in Staphylococcus aureus. J Bacteriol 183:1843–1852CrossRefGoogle Scholar
  11. 11.
    Gorwitz RJ, Kruszon-Moran D, McAllister SK, McQuillan G, McDougal LK, Fosheim GE, Jensen BJ, Killgore G, Tenover FC, Kuehnert MJ (2008) Changes in the prevalence of nasal colonization with Staphylococcus aureus in the United States, 2001–2004. J Infect Dis 197:1226–1234CrossRefGoogle Scholar
  12. 12.
    Hall JW, Yang J, Guo H, Ji Y (2017) The Staphylococcus aureus AirSR two-component system mediates reactive oxygen species resistance via transcriptional regulation of staphyloxanthin production. Infect Immun 85:e00838–e008316CrossRefGoogle Scholar
  13. 13.
    Horsburgh MJ, Aish JL, White IJ, Shaw L, Lithgow JK, Foster SJ (2002) SigmaB modulates virulence determinant expression and stress resistance: characterization of a functional rsbU strain derived from Staphylococcus aureus 8325-4. J Bacteriol 184:5457–5467CrossRefGoogle Scholar
  14. 14.
    Hu Q, Peng H, Rao X (2016) molecular events for promotion of vancomycin resistance in vancomycin intermediate Staphylococcus aureus. Front Microbiol 7:1601Google Scholar
  15. 15.
    Kossakowska-Zwierucho M, Kazmierkiewicz R, Bielawski KP, Nakonieczna J (2016) Factors determining Staphylococcus aureus susceptibility to photoantimicrobial chemotherapy: RsbU activity, staphyloxanthin level, and membrane fluidity. Front Microbiol 7:1141CrossRefGoogle Scholar
  16. 16.
    Kreiswirth BN, Lofdahl S, Betley MJ, O’Reilly M, Schlievert PM, Bergdoll MS, Novick RP (1983) The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage. Nature 305:709–712CrossRefGoogle Scholar
  17. 17.
    Kullik I, Giachino P, Fuchs T (1998) Deletion of the alternative sigma factor sigmaB in Staphylococcus aureus reveals its function as a global regulator of virulence genes. J Bacteriol 180:4814–4820Google Scholar
  18. 18.
    Liu GY, Essex A, Buchanan JT, Datta V, Hoffman HM, Bastian JF, Fierer J, Nizet V (2005) Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity. J Exp Med 202:209–215CrossRefGoogle Scholar
  19. 19.
    Liu GY, Nizet V (2009) Color me bad: microbial pigments as virulence factors. Trends Microbiol 17:406–413CrossRefGoogle Scholar
  20. 20.
    Liu H, Shang W, Hu Z, Zheng Y, Yuan J, Hu Q, Peng H, Cai X, Tan L, Li S, Zhu J, Li M, Hu X, Zhou R, Rao X, Yang Y (2018) A novel SigB(Q225P) mutation in Staphylococcus aureus retains virulence but promotes biofilm formation. Emerg Microbes Infect 7:72CrossRefGoogle Scholar
  21. 21.
    Mainous AG 3rd, Hueston WJ, Everett CJ, Diaz VA (2006) Nasal carriage of Staphylococcus aureus and methicillin-resistant S aureus in the United States, 2001–2002. Ann Fam Med 4:132–137CrossRefGoogle Scholar
  22. 22.
    McGuinness WA, Malachowa N, DeLeo FR (2017) Vancomycin resistance in Staphylococcus aureus. Yale J Biol Med 90:269–281Google Scholar
  23. 23.
    Mishra NN, Liu GY, Yeaman MR, Nast CC, Proctor RA, McKinnell J, Bayer AS (2011) Carotenoid-related alteration of cell membrane fluidity impacts Staphylococcus aureus susceptibility to host defense peptides. Antimicrob Agents Chemother 55:526–531CrossRefGoogle Scholar
  24. 24.
    Nicholas RO, Li T, McDevitt D, Marra A, Sucoloski S, Demarsh PL, Gentry DR (1999) Isolation and characterization of a sigB deletion mutant of Staphylococcus aureus. Infect Immun 67:3667–3669Google Scholar
  25. 25.
    Oliveira D, Borges A, Simoes M (2018) Staphylococcus aureus toxins and their molecular activity in infectious diseases. Toxins (Basel) 10:252CrossRefGoogle Scholar
  26. 26.
    Pelz A, Wieland KP, Putzbach K, Hentschel P, Albert K, Gotz F (2005) Structure and biosynthesis of staphyloxanthin from Staphylococcus aureus. J Biol Chem 280:32493–32498CrossRefGoogle Scholar
  27. 27.
    Sage E, Shikazono N (2017) Radiation-induced clustered DNA lesions: repair and mutagenesis. Free Radic Biol Med 107:125–135CrossRefGoogle Scholar
  28. 28.
    Sargentini NJ, Gularte NP, Hudman DA (2016) Screen for genes involved in radiation survival of Escherichia coli and construction of a reference database. Mutat Res 793–794:1–14CrossRefGoogle Scholar
  29. 29.
    Shen F, Tang X, Cheng W, Wang Y, Wang C, Shi X, An Y, Zhang Q, Liu M, Liu B, Yu L (2016) Fosfomycin enhances phagocyte-mediated killing of Staphylococcus aureus by extracellular traps and reactive oxygen species. Sci Rep 6:19262CrossRefGoogle Scholar
  30. 30.
    Singh VK, Schmidt JL, Jayaswal RK, Wilkinson BJ (2003) Impact of sigB mutation on Staphylococcus aureus oxacillin and vancomycin resistance varies with parental background and method of assessment. Int J Antimicrob Agents 21:256–261CrossRefGoogle Scholar
  31. 31.
    Singh VK, Syring M, Singh A, Singhal K, Dalecki A, Johansson T (2012) An insight into the significance of the DnaK heat shock system in Staphylococcus aureus. Int J Med Microbiol 302:242–252CrossRefGoogle Scholar
  32. 32.
    Singh VK, Vaish M, Johansson TR, Baum KR, Ring RP, Singh S, Shukla SK, Moskovitz J (2015) Significance of four methionine sulfoxide reductases in Staphylococcus aureus. PLoS ONE 10:e0117594CrossRefGoogle Scholar
  33. 33.
    Singh VK, Sirobhushanam S, Ring RP, Singh S, Gatto C, Wilkinson BJ (2018) Roles of pyruvate dehydrogenase and branched-chain alpha-keto acid dehydrogenase in branched-chain membrane fatty acid levels and associated functions in Staphylococcus aureus. J Med Microbiol 67:570–578CrossRefGoogle Scholar
  34. 34.
    Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler VG Jr (2015) Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 28:603–661CrossRefGoogle Scholar
  35. 35.
    Vaish M, Singh VK (2013) Antioxidant functions of nitric oxide synthase in a methicillin sensitive Staphylococcus aureus. Int J Microbiol 2013:312146CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Miri K. Pannu
    • 1
  • Deborah A. Hudman
    • 1
  • Neil J. Sargentini
    • 1
  • Vineet K. Singh
    • 1
    Email author
  1. 1.Department of Microbiology and Immunology, Kirksville College of Osteopathic MedicineA.T. Still University of Health SciencesKirksvilleUSA

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