{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wei Y"],"funding":["HHS | National Institutes of Health","Cecil H. and Ida Green Chair in Systems Biology Science","NIAID NIH HHS","NIGMS NIH HHS"],"pagination":["e01099-20"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8544892"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(1)"],"pubmed_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 <i>Streptococcus pneumoniae</i> and the closely related oral commensals <i>S. mitis</i> and <i>S. oralis</i> produce type IV LTAs. Herein, using liquid chromatography/mass spectrometry-based lipidomic analysis, we found that in addition to type IV LTA biosynthetic precursors, <i>S. mitis</i>, <i>S. oralis</i>, and <i>S. pneumoniae</i> also produce glycerophosphate (Gro-P)-linked dihexosyl (DH)-diacylglycerol (DAG), which is a biosynthetic precursor of type I LTA. <i>cdsA</i> and <i>pgsA</i> mutants produce DHDAG but lack (Gro-P)-DHDAG, indicating that the Gro-P moiety is derived from phosphatidylglycerol (PG), whose biosynthesis requires these genes. <i>S. mitis</i>, but not <i>S. pneumoniae</i> or <i>S. oralis</i>, encodes an ortholog of the PG-dependent type I LTA synthase, <i>ltaS</i> By heterologous expression analyses, we confirmed that <i>S. mitis</i><i>ltaS</i> confers poly(Gro-P) synthesis in both <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> and that <i>S. mitis</i><i>ltaS</i> can rescue the growth defect of an <i>S. aureus</i><i>ltaS</i> mutant. However, we do not detect a poly(Gro-P) polymer in <i>S. mitis</i> using an anti-type I LTA antibody. Moreover, Gro-P-linked DHDAG is still synthesized by an <i>S. mitis</i><i>ltaS</i> mutant, demonstrating that <i>S. mitis</i> LtaS does not catalyze Gro-P transfer to DHDAG. Finally, an <i>S. mitis</i><i>ltaS</i> mutant has increased sensitivity to human serum, demonstrating that <i>ltaS</i> confers a beneficial but currently undefined function in <i>S. mitis</i> Overall, our results demonstrate that <i>S. mitis</i>, <i>S. pneumoniae</i>, and <i>S. oralis</i> produce a Gro-P-linked glycolipid via a PG-dependent, <i>ltaS</i>-independent mechanism.<b>IMPORTANCE</b> The cell wall is a critical structural component of bacterial cells that confers important physiological functions. For pathogens, it is a site of host-pathogen interactions. In this work, we analyze the glycolipids synthesized by the mitis group streptococcal species, <i>S. pneumoniae</i>, <i>S. oralis</i>, and <i>S. mitis</i> We find that all produce the glycolipid, glycerophosphate (Gro-P)-linked dihexosyl (DH)-diacylglycerol (DAG), which is a precursor for the cell wall polymer type I lipoteichoic acid in other bacteria. We investigate whether the known enzyme for type I LTA synthesis, LtaS, plays a role in synthesizing this molecule in <i>S. mitis</i> Our results indicate that a novel mechanism is responsible. Our results are significant because they identify a novel feature of <i>S. pneumoniae</i>, <i>S. oralis</i>, and <i>S. mitis</i> glycolipid biology."],"journal":["mSphere"],"pubmed_title":["Streptococcus pneumoniae, S. mitis, and S. oralis Produce a Phosphatidylglycerol-Dependent, <i>ltaS</i>-Independent Glycerophosphate-Linked Glycolipid."],"pmcid":["PMC8544892"],"funding_grant_id":["R56 AI139105","R56AI139105","U54GM069338","R21AI130666","U54 GM069338","R21 AI130666","R01AI148366","R01 AI148366"],"pubmed_authors":["Guan Z","Wall AM","Joyce LR","Palmer KL","Wei Y"],"additional_accession":[]},"is_claimable":false,"name":"Streptococcus pneumoniae, S. mitis, and S. oralis Produce a Phosphatidylglycerol-Dependent, <i>ltaS</i>-Independent Glycerophosphate-Linked Glycolipid.","description":"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 <i>Streptococcus pneumoniae</i> and the closely related oral commensals <i>S. mitis</i> and <i>S. oralis</i> produce type IV LTAs. Herein, using liquid chromatography/mass spectrometry-based lipidomic analysis, we found that in addition to type IV LTA biosynthetic precursors, <i>S. mitis</i>, <i>S. oralis</i>, and <i>S. pneumoniae</i> also produce glycerophosphate (Gro-P)-linked dihexosyl (DH)-diacylglycerol (DAG), which is a biosynthetic precursor of type I LTA. <i>cdsA</i> and <i>pgsA</i> mutants produce DHDAG but lack (Gro-P)-DHDAG, indicating that the Gro-P moiety is derived from phosphatidylglycerol (PG), whose biosynthesis requires these genes. <i>S. mitis</i>, but not <i>S. pneumoniae</i> or <i>S. oralis</i>, encodes an ortholog of the PG-dependent type I LTA synthase, <i>ltaS</i> By heterologous expression analyses, we confirmed that <i>S. mitis</i><i>ltaS</i> confers poly(Gro-P) synthesis in both <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> and that <i>S. mitis</i><i>ltaS</i> can rescue the growth defect of an <i>S. aureus</i><i>ltaS</i> mutant. However, we do not detect a poly(Gro-P) polymer in <i>S. mitis</i> using an anti-type I LTA antibody. Moreover, Gro-P-linked DHDAG is still synthesized by an <i>S. mitis</i><i>ltaS</i> mutant, demonstrating that <i>S. mitis</i> LtaS does not catalyze Gro-P transfer to DHDAG. Finally, an <i>S. mitis</i><i>ltaS</i> mutant has increased sensitivity to human serum, demonstrating that <i>ltaS</i> confers a beneficial but currently undefined function in <i>S. mitis</i> Overall, our results demonstrate that <i>S. mitis</i>, <i>S. pneumoniae</i>, and <i>S. oralis</i> produce a Gro-P-linked glycolipid via a PG-dependent, <i>ltaS</i>-independent mechanism.<b>IMPORTANCE</b> The cell wall is a critical structural component of bacterial cells that confers important physiological functions. For pathogens, it is a site of host-pathogen interactions. In this work, we analyze the glycolipids synthesized by the mitis group streptococcal species, <i>S. pneumoniae</i>, <i>S. oralis</i>, and <i>S. mitis</i> We find that all produce the glycolipid, glycerophosphate (Gro-P)-linked dihexosyl (DH)-diacylglycerol (DAG), which is a precursor for the cell wall polymer type I lipoteichoic acid in other bacteria. We investigate whether the known enzyme for type I LTA synthesis, LtaS, plays a role in synthesizing this molecule in <i>S. mitis</i> Our results indicate that a novel mechanism is responsible. Our results are significant because they identify a novel feature of <i>S. pneumoniae</i>, <i>S. oralis</i>, and <i>S. mitis</i> glycolipid biology.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Feb","modification":"2026-06-17T06:23:57.876Z","creation":"2025-02-19T01:26:03.521Z"},"accession":"S-EPMC8544892","cross_references":{"pubmed":["33627509"],"doi":["10.1128/mSphere.01099-20"]}}