Nature 563, 705–709 (2018)

Methicillin-resistant Staphylococcus aureus (MRSA) strains are thought to succeed by evading the host immune system. Though humans have antibodies against S. aureus, a successful vaccine has not been developed. Most of these host antibodies are directed against wall teichoic acid (WTA), a ribitol-phosphate (RboP) surface polymer modified by N-acetylglucosamine (GlcNAc). To better understand the basis of increased fitness and pathogenicity, Gerlach et al. examined S. aureus genomes for paralogs of WTA biosynthesis genes and found a protein, TarP, encoded by three S. aureus prophages with similarity to the standard WTA glycosyltransferase TarS. TarP is sufficient for WTA glycosylation and for conferring several WTA functional properties, although it catalyzes glycosylation of RboP at a different site compared to TarS. A structural study of TarP with WTA could explain this alternate WTA glycosylation and a reduced affinity of TarS for WTA compared to TarP. Finally, the authors found that, compared to TarP, TarS more strongly increases IgG binding and immunogenicity. These results suggest that TarP-expressing S. aureus are less susceptible to detection and elimination by the host immune system and reveal a new target for vaccines and for small molecule inhibition.

Credit: Nature