Longitudinal proliferation mapping in vivo reveals NADPH oxidase-mediated dampening of Staphylococcus aureus growth rates within neutrophils.

Elena A Seiß, Anna Krone, Pauline Formaglio, Oliver Goldmann, Susanne Engelmann, Burkhart Schraven, Eva Medina, Andreas J Müller
Author Information
  1. Elena A Seiß: Institute of Molecular and Clinical Immunology, Health Campus Immunology Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University, Leipziger Strasse 44, 39120, Magdeburg, Germany. elena.seiss@med.ovgu.de.
  2. Anna Krone: Institute of Molecular and Clinical Immunology, Health Campus Immunology Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University, Leipziger Strasse 44, 39120, Magdeburg, Germany.
  3. Pauline Formaglio: Institute of Molecular and Clinical Immunology, Health Campus Immunology Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University, Leipziger Strasse 44, 39120, Magdeburg, Germany.
  4. Oliver Goldmann: Infection Immunology, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany.
  5. Susanne Engelmann: Microbial Proteomics, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany.
  6. Burkhart Schraven: Institute of Molecular and Clinical Immunology, Health Campus Immunology Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University, Leipziger Strasse 44, 39120, Magdeburg, Germany.
  7. Eva Medina: Infection Immunology, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany.
  8. Andreas J Müller: Institute of Molecular and Clinical Immunology, Health Campus Immunology Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University, Leipziger Strasse 44, 39120, Magdeburg, Germany. andreas.mueller@med.ovgu.de. ORCID

Abstract

Upon the onset of inflammatory responses, bacterial pathogens are confronted with altered tissue microenvironments which can critically impact on their metabolic activity and growth. Changes in these parameters have however remained difficult to analyze over time, which would be critical to dissect the interplay between the host immune response and pathogen physiology. Here, we established an in vivo biosensor for measuring the growth rates of Staphylococcus aureus (S. aureus) on a single cell-level over days in an ongoing cutaneous infection. Using intravital 2-photon imaging and quantitative fluorescence microscopy, we show that upon neutrophil recruitment to the infection site and bacterial uptake, non-lethal dampening of S. aureus proliferation occurred. This inhibition was supported by NADPH oxidase activity. Therefore, reactive oxygen production contributes to pathogen containment within neutrophils not only by killing S. aureus, but also by restricting the growth rate of the bacterium.

References

  1. PLoS Pathog. 2018 Oct 22;14(10):e1007374 [PMID: 30346994]
  2. Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3746-51 [PMID: 20133586]
  3. Dev Cell. 2018 Mar 12;44(5):542-553 [PMID: 29533770]
  4. Immunity. 2014 Jul 17;41(1):63-74 [PMID: 24981853]
  5. N Engl J Med. 2000 Dec 7;343(23):1703-14 [PMID: 11106721]
  6. Cell. 2014 Aug 14;158(4):722-733 [PMID: 25126781]
  7. Nat Immunol. 2014 Jan;15(1):45-53 [PMID: 24270515]
  8. Transfusion. 1997 Apr;37(4):423-35 [PMID: 9111281]
  9. J Immunol. 2000 Apr 1;164(7):3713-22 [PMID: 10725730]
  10. Infect Immun. 2007 Feb;75(2):1017-24 [PMID: 17118986]
  11. Antimicrob Agents Chemother. 2013 Apr;57(4):1648-53 [PMID: 23335744]
  12. Front Immunol. 2018 Jun 27;9:1468 [PMID: 30013554]
  13. Appl Environ Microbiol. 2013 Dec;79(23):7116-21 [PMID: 24038684]
  14. Nat Methods. 2015 May;12(5):445-52 [PMID: 25775045]
  15. J Exp Med. 2016 Jun 27;213(7):1141-51 [PMID: 27325887]
  16. Nature. 2011 May 22;474(7351):385-9 [PMID: 21602824]
  17. Nat Microbiol. 2017 Jan 23;2:16268 [PMID: 28112722]
  18. mBio. 2018 Jul 17;9(4): [PMID: 30018109]
  19. Am J Pathol. 2012 Oct;181(4):1327-37 [PMID: 22885107]
  20. Immunity. 2012 Aug 24;37(2):351-63 [PMID: 22683126]
  21. Infect Immun. 2012 Apr;80(4):1455-66 [PMID: 22252868]
  22. Transfusion. 2000 Dec;40(12):1503-7 [PMID: 11134571]
  23. J Innate Immun. 2010;2(6):560-75 [PMID: 20587998]
  24. PLoS One. 2008;3(12):e3944 [PMID: 19079591]
  25. Curr Opin Microbiol. 2015 Feb;23:42-8 [PMID: 25461571]
  26. EMBO Mol Med. 2011 Mar;3(3):129-41 [PMID: 21268281]
  27. Blood. 2008 Dec 15;112(13):5202-11 [PMID: 18755982]
  28. Semin Immunopathol. 2012 Mar;34(2):237-59 [PMID: 22080185]
  29. Cell Microbiol. 2016 Apr;18(4):514-35 [PMID: 26408990]

MeSH Term

Animals
Cell Proliferation
Host-Pathogen Interactions
Mice
NADPH Oxidases
Neutrophil Infiltration
Neutrophils
Reactive Oxygen Species
Staphylococcal Infections
Staphylococcus aureus

Chemicals

Reactive Oxygen Species
NADPH Oxidases

Word Cloud

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