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Suppression of antimicrobial peptide expression by ureaplasma species

Li Xiao1, Donna M Crabb, Yuling Dai

  • 1Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Infection and Immunity
|February 5, 2014
PubMed

Insights

Antimicrobial peptides (AMPs) show activity against Ureaplasma, but these bacteria downregulate AMP gene expression. This suppression of host defense may enable chronic Ureaplasma colonization and infection.

Area of Science:

  • Microbiology
  • Immunology
  • Genetics

Background:

  • Ureaplasma species frequently colonize the urogenital tract and are linked to serious infections in adults and neonates.
  • The mechanisms enabling chronic Ureaplasma colonization remain unclear.
  • Host innate immune responses, particularly antimicrobial peptides (AMPs), are investigated as potential factors influencing infection outcomes.

Purpose of the Study:

  • To investigate the role of host antimicrobial peptides (AMPs) in Ureaplasma infections.
  • To determine if Ureaplasma influences the expression of host defense genes, including AMPs.
  • To assess the in vitro antimicrobial activity of synthetic AMPs against Ureaplasma species.

Main Methods:

  • THP-1 cells were co-cultured with Ureaplasma parvum and U. urealyticum.
  • Gene expression of host defense genes was quantified using real-time PCR.
  • In vitro antimicrobial activity of synthetic AMPs was assessed via flow cytometry.
  • Chromatin immunoprecipitation (ChIP) and DNA methylation analysis were performed on AMP gene promoters.

Main Results:

  • Ureaplasma infection led to significant downregulation of AMP genes (DEFB1, DEFA5, DEFA6, CAMP) but upregulation of TNFA and IL-8.
  • Synthetic AMPs LL-37, hBD-3, and hBD-1 demonstrated in vitro activity against Ureaplasma species.
  • Downregulation of AMP genes correlated with altered chromatin modifications, specifically decreased histone H3K9 acetylation during U. parvum infection.
  • No changes in DNA methylation were observed in AMP promoter regions.

Conclusions:

  • Antimicrobial peptides (AMPs) exhibit direct antimicrobial effects against Ureaplasma species in vitro.
  • Ureaplasma appears to suppress host AMP gene expression, potentially through epigenetic modifications like histone acetylation.
  • This suppression of AMPs may be a critical mechanism for Ureaplasma to evade host innate immunity and establish chronic colonization or infection.

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