Intradermal Immunization with Wall Teichoic Acid (WTA) Elicits and Augments an Anti-WTA IgG Response that Protects Mice from Methicillin-Resistant Staphylococcus aureus Infection Independent of Mannose-Binding Lectin Status
نویسندگان
چکیده
The objectives of this study were to investigate the immune response to intradermal immunization with wall teichoic acid (WTA) and the effect of MBL deficiency in a murine model of infection with methicillin-resistant Staphylococcus aureus (MRSA). WTA is a bacterial cell wall component that is implicated in invasive infection. We tested susceptibility to MRSA infection in wild type (WT) and MBL deficient mice using two strains of MRSA: MW2, a community-associated MRSA (CA-MRSA); and COL, a healthcare-associated MRSA (HA-MRSA). We also performed in vitro assays to investigate the effects of anti-WTA IgG containing murine serum on complement activation and bacterial growth in whole blood. We found that MBL knockout (KO) mice are relatively resistant to a specific MRSA strain, MW2 CA-MRSA, compared to WT mice, while both strains of mice had similar susceptibility to a different strain, COL HA-MRSA. Intradermal immunization with WTA elicited and augmented an anti-WTA IgG response in both WT and MBL KO mice. WTA immunization significantly reduced susceptibility to both MW2 CA-MRSA and COL HA-MRSA, independent of the presence of MBL. The protective mechanisms of anti-WTA IgG are mediated at least in part by complement activation and clearance of bacteria from blood. The significance of these findings is that 1) Intradermal immunization with WTA induces production of anti-WTA IgG; and 2) This anti-WTA IgG response protects from infection with both MW2 CA-MRSA and COL HA-MRSA even in the absence of MBL, the deficiency of which is common in humans.
منابع مشابه
Specific serum Ig recognizing staphylococcal wall teichoic acid induces complement-mediated opsonophagocytosis against Staphylococcus aureus.
Wall teichoic acid (WTA) of Staphylococcus aureus is a major cell envelope-associated glycopolymer that is a key molecule in promoting colonization during S. aureus infection. The complement system plays a key role in the opsonization and clearance of pathogens. We recently reported that S. aureus WTA functions as a ligand of human serum mannose-binding lectin (MBL), a recognition molecule of t...
متن کاملAn accessory wall teichoic acid glycosyltransferase protects Staphylococcus aureus from the lytic activity of Podoviridae
Many Staphylococcus aureus have lost a major genetic barrier against phage infection, termed clustered regularly interspaced palindromic repeats (CRISPR/cas). Hence, S. aureus strains frequently exchange genetic material via phage-mediated horizontal gene transfer events, but, in turn, are vulnerable in particular to lytic phages. Here, a novel strategy of S. aureus is described, which protects...
متن کاملWall teichoic acid protects Staphylococcus aureus against antimicrobial fatty acids from human skin.
Skin-colonizing gram-positive bacteria produce wall teichoic acids (WTAs) or related glycopolymers for unclear reasons. Using a WTA-deficient Staphylococcus aureus mutant, we demonstrated that WTA confers resistance to antimicrobial fatty acids from human sebaceous glands by preventing fatty acid binding. Thus, WTA is probably important for bacterial skin colonization.
متن کاملDisruption of d-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the β-lactam resistance modifier (−)-epicatechin gallate
OBJECTIVES The naturally occurring polyphenol (-)-epicatechin gallate (ECg) increases oxacillin susceptibility in mecA-containing strains of Staphylococcus aureus. Decreased susceptibility to lysostaphin suggests alterations to the wall teichoic acid (WTA) content of ECg-grown bacteria. Changes in WTA structure in response to ECg were determined. METHODS Nuclear magnetic resonance spectroscop...
متن کاملWall Teichoic Acid Glycosylation Governs Staphylococcus aureus Nasal Colonization
UNLABELLED Nasal colonization by the human pathogen Staphylococcus aureus is a major risk factor for hospital- and community-acquired infections. A key factor required for nasal colonization is a cell surface-exposed zwitterionic glycopolymer, termed wall teichoic acid (WTA). However, the precise mechanisms that govern WTA-mediated nasal colonization have remained elusive. Here, we report that ...
متن کامل