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Volume 8, Issue 12

Genetic diversity of wall teichoic acid glycosyltransferases affects immune recognition Open Access

Abstract

is a leading cause of skin and soft tissue infections and systemic infections. Wall teichoic acids (WTAs) are cell wall-anchored glycopolymers that are important for nasal colonization, phage-mediated horizontal gene transfer, and antibiotic resistance. WTAs consist of a polymerized ribitol phosphate (RboP) chain that can be glycosylated with -acetylglucosamine (GlcNAc) by three glycosyltransferases: TarS, TarM, and TarP. TarS and TarP modify WTA with β-linked GlcNAc at the C-4 (β1,4-GlcNAc) and the C-3 position (β1,3-GlcNAc) of the RboP subunit, respectively, whereas TarM modifies WTA with α-linked GlcNAc at the C-4 position (α1,4-GlcNAc). Importantly, these WTA glycosylation patterns impact immune recognition and clearance of . Previous studies suggest that is near-universally present within the population, whereas a smaller proportion co-contain either or . To gain more insight into the presence and genetic variation of , and in the population, we analysed a collection of 25 652 . genomes within the PubMLST database. Over 99 % of isolates contained . Co-presence of / or / occurred in 37 and 7 % of isolates, respectively, and was associated with specific clonal complexes. We also identified 26 isolates (0.1 %) that contained all three glycosyltransferase genes. At sequence level, we identified alleles with amino acid substitutions in critical enzymatic residues or with premature stop codons. Several variants were expressed in a -negative strain. Analysis using specific monoclonal antibodies and human langerin showed that WTA glycosylation was severely attenuated or absent. Overall, our data provide a broad overview of the genetic diversity of the three WTA glycosyltransferases in the population and the functional consequences for immune recognition.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): glycosylation , PubMLST , Staphylococcus aureus , tar glycosyltransferases and wall teichoic acid
Funding
This study was supported by the:
  • Wellcome Trust
    • Principle Award Recipient: ApplicableNot
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Award 09150181910001)
    • Principle Award Recipient: M. van SorgeNina
© 2022 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2022-12-07
2024-04-19
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Genetic diversity of Staphylococcus aureus wall teichoic acid glycosyltransferases affects immune recognition
M Gen 8, 000902 (2022); https://doi.org/10.1099/mgen.0.000902
/content/journal/mgen/10.1099/mgen.0.000902
/content/journal/mgen/10.1099/mgen.0.000902
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