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Constitutive and inflammation-dependent antimicrobial peptides produced by epithelium are differentially processed

Inga-Maria Frick1, Sara L Nordin, Maria Baumgarten

  • 1Section for Infection Medicine, Department of Clinical Sciences, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.

Journal of Immunology (Baltimore, Md. : 1950)
|September 16, 2011
PubMed

Insights

This study reveals how the skin bacterium Finegoldia magna survives antimicrobial peptides (AMPs) like midkine (MK) and BRAK/CXCL14. F. magna uses its protease SufA to degrade these AMPs, while also producing FAF to neutralize them, aiding its survival.

Area of Science:

  • Microbiology
  • Immunology
  • Biochemistry

Background:

  • Epithelial barriers produce antimicrobial peptides (AMPs) like midkine (MK) and BRAK/CXCL14 to maintain host defense.
  • The skin commensal Finegoldia magna and the pathogen Streptococcus pyogenes inhabit environments rich in these AMPs.
  • Inflammation alters the expression of MK and BRAK/CXCL14, impacting the local antimicrobial milieu.

Purpose of the Study:

  • To investigate the interactions between F. magna, S. pyogenes, and host antimicrobial peptides (AMPs) in the skin.
  • To determine the mechanisms by which F. magna survives exposure to MK and BRAK/CXCL14.
  • To compare the strategies employed by a commensal and a pathogen in combating host defenses.

Main Methods:

  • Bactericidal assays using MK, BRAK/CXCL14, human beta-defensins (hBD)-2, and hBD-3 against F. magna and S. pyogenes.
  • Enzymatic degradation studies using F. magna protease SufA and S. pyogenes protease SpeB on AMPs.
  • Neutralization assays using F. magna protein FAF and S. pyogenes protein SIC.
  • Immunoelectron microscopy for quantitation and colocalization of molecules in biological samples.

Main Results:

  • MK and BRAK/CXCL14, along with hBD-2 and hBD-3, exhibited bactericidal activity against both F. magna and S. pyogenes.
  • F. magna's protease SufA degraded MK and BRAK/CXCL14, with fragments showing enhanced activity against S. pyogenes.
  • F. magna's protein FAF and S. pyogenes' SpeB protease neutralized AMPs, with FAF being more effective; SpeB degraded all tested AMPs.
  • Significant levels and interactions of these molecules were observed in vivo and ex vivo samples.

Conclusions:

  • F. magna employs sophisticated strategies, including protease degradation and protein neutralization of host AMPs, to ensure its survival.
  • The differential degradation and neutralization of AMPs by F. magna and S. pyogenes highlight distinct survival tactics.
  • These findings provide insights into the complex interplay between commensal bacteria, pathogens, and host immune defenses in the skin microbiome.

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