دورية أكاديمية
The Phospholipase A1 Activity of Glycerol Ester Hydrolase (Geh) Is Responsible for Extracellular 2-12( S )-Methyltetradecanoyl-Lysophosphatidylglycerol Production in Staphylococcus aureus.
العنوان: | The Phospholipase A1 Activity of Glycerol Ester Hydrolase (Geh) Is Responsible for Extracellular 2-12( S )-Methyltetradecanoyl-Lysophosphatidylglycerol Production in Staphylococcus aureus. |
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المؤلفون: | Subramanian C; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Frank MW; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Yun MK; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Rock CO; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. |
المصدر: | MSphere [mSphere] 2023 Apr 20; Vol. 8 (2), pp. e0003123. Date of Electronic Publication: 2023 Mar 28. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101674533 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2379-5042 (Electronic) Linking ISSN: 23795042 NLM ISO Abbreviation: mSphere Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, DC : American Society for Microbiology, [2015]- |
مواضيع طبية MeSH: | Staphylococcus aureus* , Staphylococcal Infections*, Humans ; Phospholipases A1/metabolism ; Glycerol/metabolism ; Lysophospholipids/metabolism ; Esterases/metabolism ; Lipase/genetics ; Lipase/metabolism ; Phosphatidylglycerols ; Esters |
مستخلص: | Phosphatidylglycerol (PG) is the major membrane phospholipid of Staphylococcus aureus and predominately consists of molecular species with ≥16-carbon acyl chains in the 1-position and anteiso 12( S )-methyltetradecaonate (a15) esterified at the 2-position. The analysis of the growth media for PG-derived products shows S. aureus releases essentially pure 2-12( S )-methyltetradecanoyl- sn -glycero-3-phospho-1'- sn -glycerol (a15:0-LPG) derived from the hydrolysis of the 1-position of PG into the environment. The cellular lysophosphatidylglycerol (LPG) pool is dominated by a15-LPG but also consists of ≥16-LPG species arising from the removal of the 2-position. Mass tracing experiments confirmed a15-LPG was derived from isoleucine metabolism. A screen of candidate secreted lipase knockout strains pinpointed glycerol ester hydrolase ( geh ) as the gene required for generating extracellular a15-LPG, and complementation of a Δ geh strain with a Geh expression plasmid restored extracellular a15-LPG formation. Orlistat, a covalent inhibitor of Geh, also attenuated extracellular a15-LPG accumulation. Purified Geh hydrolyzed the 1-position acyl chain of PG and generated only a15-LPG from a S. aureus lipid mixture. The Geh product was 2-a15-LPG, which spontaneously isomerizes with time to a mixture of 1- and 2-a15-LPG. Docking PG in the Geh active site provides a structural rationale for the positional specificity of Geh. These data demonstrate a physiological role for Geh phospholipase A1 activity in S. aureus membrane phospholipid turnover. IMPORTANCE Glycerol ester hydrolase, Geh, is an abundant secreted lipase whose expression is controlled by the accessory gene regulator (Agr) quorum-sensing signal transduction pathway. Geh is thought to have a role in virulence based on its ability to hydrolyze host lipids at the infection site to provide fatty acids for membrane biogenesis and substrates for oleate hydratase, and Geh inhibits immune cell activation by hydrolyzing lipoprotein glycerol esters. The discovery that Geh is the major contributor to the formation and release of a15-LPG reveals an unappreciated physiological role for Geh acting as a phospholipase A1 in the degradation of S. aureus membrane phosphatidylglycerol. The role(s) for extracellular a15-LPG in S. aureus biology remain to be elucidated. |
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معلومات مُعتمدة: | P30 CA021765 United States CA NCI NIH HHS; R01 GM034496 United States GM NIGMS NIH HHS; R37 GM034496 United States GM NIGMS NIH HHS; GM034496 United States GM NIGMS NIH HHS |
فهرسة مساهمة: | Keywords: Staphylococcus aureus; fatty acids; glycerol ester hydrolase; membrane; phospholipase A1; phospholipid; phospholipids; virulence |
المشرفين على المادة: | 0 (lysophosphatidylglycerol) EC 3.1.1.32 (Phospholipases A1) PDC6A3C0OX (Glycerol) 0 (Lysophospholipids) EC 3.1.- (Esterases) EC 3.1.1.3 (Lipase) 0 (Phosphatidylglycerols) 0 (Esters) |
تواريخ الأحداث: | Date Created: 20230328 Date Completed: 20230424 Latest Revision: 20240522 |
رمز التحديث: | 20240522 |
مُعرف محوري في PubMed: | PMC10117073 |
DOI: | 10.1128/msphere.00031-23 |
PMID: | 36976028 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2379-5042 |
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DOI: | 10.1128/msphere.00031-23 |