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Silkworm apolipophorin protein inhibits Staphylococcus aureus virulence

Yuichi Hanada1, Kazuhisa Sekimizu, Chikara Kaito

  • 1Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 3-1, 7-chome, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

The Journal of Biological Chemistry
|September 23, 2011
PubMed

Insights

Silkworm hemolymph contains apolipophorin (ApoLp), which inhibits Staphylococcus aureus hemolysin production. This finding suggests ApoLp plays a role in insect immunity and has conserved functions in mammals.

Area of Science:

  • Insect immunity
  • Microbial pathogenesis
  • Biochemistry

Background:

  • Staphylococcus aureus produces hemolysins, virulence factors contributing to infection.
  • Silkworm hemolymph possesses antimicrobial properties.
  • The specific components and mechanisms of silkworm hemolymph's antimicrobial activity require elucidation.

Purpose of the Study:

  • To identify and characterize the factor in silkworm hemolymph that inhibits Staphylococcus aureus hemolysin production.
  • To investigate the mechanism by which this factor affects S. aureus virulence gene expression.
  • To explore the potential conserved function of this factor in mammalian systems.

Main Methods:

  • Purification of inhibitory factor from silkworm hemolymph using protein fractionation techniques.
  • N-terminal amino acid sequencing to identify purified proteins.
  • Quantitative analysis of S. aureus virulence gene expression (hla, hlb, saeRS, RNAIII) via RT-qPCR.
  • Experimental infection models involving silkworm hemolymph injection and anti-ApoLp antibody administration.
  • In vitro assays using hog gastric mucin to assess its effect on S. aureus virulence genes.

Main Results:

  • Apolipophorin (ApoLp), composed of apolipophorin I and II, was identified as the primary inhibitor of hemolysin production.
  • Purified ApoLp significantly decreased the expression of S. aureus genes hla, hlb, saeRS, and RNAIII.
  • Silkworms injected with anti-ApoLp antibodies showed increased susceptibility to S. aureus infection.
  • Hog gastric mucin, a mammalian homologue, also reduced S. aureus hla and hlb expression.

Conclusions:

  • Apolipophorin in silkworm hemolymph acts as a key component in the innate immune defense against Staphylococcus aureus by suppressing hemolysin production.
  • The identified mechanism involves downregulating critical virulence and regulatory genes in S. aureus.
  • The conserved inhibitory activity of apolipophorin and its mammalian homologue, mucin, highlights a potentially ancient defense mechanism against bacterial pathogens.

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