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

Kazue Takahashi,Elahna Paul,Jang-Hyun An,Patience Moyo,Lorencia Chigweshe,Bok Luel Lee,Kenji Kurokawa,Dong-Jun Jung,Michael Otto

doi:10.1371/journal.pone.0069739

Kazue Takahashi, Elahna Paul + Show 7 more

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https://doi.org/10.1371/journal.pone.0069739

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Abstract

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.

Highlights

Staphylococcus aureus, a Gram-positive bacterium, is a common commensal organism on skin and mucosa that can cause serious infections in the skin and other soft tissues, bones and blood [1]
The morbidity and mortality of S. aureus infection have greatly increased with the rapid emergence of a much more virulent and antibiotic resistant strain that is identified by its resistance to the antibiotic methicillin, and which is known as methicillinresistant S. aureus (MRSA) [1,2,3]
These results demonstrate that the kidney is susceptible to abscess formation, and that mannose-binding lectin (MBL) has a variable role depending on the S. aureus strain, in that MBL deficiency has little effect on COL HA-MRSA infection whereas it contributes to decreased MW2 CA-MRSA infection [10]

Summary

Introduction

Staphylococcus aureus, a Gram-positive bacterium, is a common commensal organism on skin and mucosa that can cause serious infections in the skin and other soft tissues, bones and blood [1]. All strains of S. aureus, including MRSA, are covered by a thick cell wall containing peptidoglycan, lipoteichoic acid (LTA) and wall teichoic acid (WTA) [4,5]. WTA of S. aureus is a glycopolymer that covalently links to peptidoglycan. It is composed of an N-acetylmannosamine (ManNAc)-(b-1,3)-Nacetylglucosamine (GlcNAc) disaccharide with two glycerol phosphates, followed by 10 to 40 ribitol phosphate repeating units [4,6]. WTA has been identified as an adhesion molecule that binds to host cells and promotes bacterial colonization and tissue invasion [7,8,9,10]

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