School of Podiatric Medicine Publications and Presentations
Document Type
Article
Publication Date
2-24-2021
Abstract
Lipoteichoic acid (LTA) is a Gram-positive bacterial cell surface polymer that participates in host-microbe interactions. It was previously reported that the major human pathogen Streptococcus pneumoniae and the closely related oral commensals S. mitis and S. oralis produce type IV LTAs. Herein, using liquid chromatography/mass spectrometry-based lipidomic analysis, we found that in addition to type IV LTA biosynthetic precursors, S. mitis, S. oralis, and S. pneumoniae also produce glycerophosphate (Gro-P)-linked dihexosyl (DH)-diacylglycerol (DAG), which is a biosynthetic precursor of type I LTA. cdsA and pgsA mutants produce DHDAG but lack (Gro-P)-DHDAG, indicating that the Gro-P moiety is derived from phosphatidylglycerol (PG), whose biosynthesis requires these genes. S. mitis, but not S. pneumoniae or S. oralis, encodes an ortholog of the PG-dependent type I LTA synthase, ltaS. By heterologous expression analyses, we confirmed that S. mitis ltaS confers poly(Gro-P) synthesis in both Escherichia coli and Staphylococcus aureus and that S. mitis ltaS can rescue the growth defect of an S. aureus ltaS mutant. However, we do not detect a poly(Gro-P) polymer in S. mitis using an anti-type I LTA antibody. Moreover, Gro-P-linked DHDAG is still synthesized by an S. mitis ltaS mutant, demonstrating that S. mitis LtaS does not catalyze Gro-P transfer to DHDAG. Finally, an S. mitis ltaS mutant has increased sensitivity to human serum, demonstrating that ltaS confers a beneficial but currently undefined function in S. mitis. Overall, our results demonstrate that S. mitis, S. pneumoniae, and S. oralis produce a Gro-P-linked glycolipid via a PG-dependent, ltaS-independent mechanism.
Recommended Citation
Wei, Y., Joyce, L. R., Wall, A. M., Guan, Z., & Palmer, K. L. (2021). Streptococcus pneumoniae, S. mitis, and S. oralis produce a phosphatidylglycerol-dependent, ltaS-independent glycerophosphate-linked glycolipid. Msphere, 6(1), 10-1128. https://doi.org/10.1128/msphere.01099-20
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
mSphere
DOI
10.1128/msphere.01099-20
Comments
© 2021 Wei et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International license.