Inhibitory role for D-alanylation of wall teichoic acid in activation of insect Toll pathway by peptidoglycan of Staphylococcus aureus.

Abstract

Pathogenic bacteria mitigate host immunity to establish infections, but the mechanism of this bacterial action has not been fully elucidated. To search for cell wall components that modulate innate immune responses in host organisms, we examined Staphylococcus aureus mutants, which were deficient in components of the cell wall, for pathogenicity in Drosophila. A mutation of dltA, which is responsible for the D-alanylation of teichoic acids, brought about an increase in the survival rate of adult flies that had received a septic infection with the bacteria. The growth of dltA-deficient S. aureus in adult flies was less efficient than that of the parental strain. The level of mRNA of Toll pathway-dependent antimicrobial peptides was higher in flies infected with the dltA mutant than that observed after the infection with the parental strain. The defective phenotype associated with the mutation of dltA, reduced pathogenicity and growth, was not evident in flies lacking the Toll pathway. Finally, a fraction of peptidoglycan prepared from the dltA mutant induced the expression of mRNA of a Toll-dependent antimicrobial peptide in flies and was bound by peptidoglycan recognition protein-SA in vitro more effectively than that obtained from the parental strain, and this difference was lost after the removal of wall teichoic acid from peptidoglycan. Taken together, we conclude that D-alanylated wall teichoic acid of S. aureus mitigates a Toll-mediated humoral response in Drosophila interfering with the recognition of peptidoglycan by a pattern recognition receptor.

• Authors: Yukichika Tabuchi, Akiko Shiratsuchi, Kenji Kurokawa, Ji Hee Gong, Kazuhisa Sekimizu, Bok Luel Lee, Yoshinobu Nakanishi
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 4 Pg. 2424-31 (Aug 15 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20639481 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Drosophila Proteins
• Peptidoglycan
• Teichoic Acids
• Tl protein, Drosophila
• Toll-Like Receptors
• DRS protein, Drosophila
• Carbon-Oxygen Ligases
• Alanine

Topics

• Alanine (metabolism)
• Animals
• Bacterial Proteins (genetics, metabolism)
• Blotting, Western
• Carbon-Oxygen Ligases (genetics, metabolism)
• Cell Wall (chemistry, metabolism)
• Drosophila Proteins (genetics, metabolism)
• Drosophila melanogaster (genetics, metabolism, microbiology)
• Host-Pathogen Interactions
• Male
• Mutation
• Peptidoglycan (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Staphylococcus aureus (genetics, metabolism, physiology)
• Teichoic Acids (chemistry, metabolism)
• Time Factors
• Toll-Like Receptors (genetics, metabolism)