A novel lipopeptide from skin commensal activates TLR2/CD36-p38 MAPK signaling to increase antibacterial defense against bacterial infection

PLoS One. 2013;8(3):e58288. doi: 10.1371/journal.pone.0058288. Epub 2013 Mar 5.

Abstract

Staphylococcus epidermidis (S.epidermidis) plays important protective roles by directly producing or by stimulating hosts to produce antimicrobial peptides (AMPs) against pathogenic infections. Although several AMPs from S.epidermidis have been identified, molecules that stimulate hosts to produce AMPs remain largly unknown. Here we demonstrate that a new lipopeptide (named LP01) purified from S.epidermidis culture media has a unique structure with heneicosanoic acid (21 carbons) binding to lysine(11) of a peptide chain. In vitro LP01 increased the expression of β-defensin 2(hBD2) and hBD3 in neonatal human epidermal keratinocytes(NHEK), leading to increased capacity of cell lysates to inhibit the growth of S.aureus. In vivo LP01 induced the expression of mouse β-defensin 4(mBD4) to decrease the survival of local S.aureus in skin and systemic S.aureus survival in liver. The induction of beta-defensins by LP01 was dependent on TLR2 as Tlr2-deficient mice had decreased mBD4. Furthermore, knockdown of CD36 decreased the expression of hBD2 and hBD3, and p38 MAPK inhibitor significantly inhibited the expression of hBDs induced by LP01.Taken together, these findings demonstrate that lipopeptide LP01 from normal commensal S.epidermidis increases antimicrobial peptide hBD2 and hBD3 expression via the activation of TLR2/CD36-p38 MAPK, thus enhancing antimicrobial defense against pathogenic infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • CD36 Antigens / metabolism
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Humans
  • Keratinocytes / cytology
  • Lipopeptides / pharmacology*
  • Liver / microbiology
  • MAP Kinase Signaling System*
  • Mice
  • Skin / microbiology*
  • Staphylococcal Skin Infections / prevention & control*
  • Staphylococcus aureus / drug effects
  • Staphylococcus epidermidis / metabolism
  • Toll-Like Receptor 2 / metabolism
  • beta-Defensins / metabolism
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Bacterial Agents
  • CD36 Antigens
  • Lipopeptides
  • TLR2 protein, human
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • beta-Defensins
  • p38 Mitogen-Activated Protein Kinases

Grant support

This work was supported by National Natural Science Foundation of China grants (NSFC) 81072422, 31222021&31170867, grants 11QA1401900, 12ZZ039 to Yuping Lai, NSFC grant 31100109 to Deming Jiang, Shanghai Natural science Foundation grant11ZR1409900 to Meiling Zhang, the program for professor of Special Appointment (Eastern Scholar) at Shanghai Institutions (Yuping Lai), and the Science and Technology Commission of Shanghai Municipality grant 11DZ2260300. Part of in-vitro studies was also supported by Johnson and Johnson. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.