Staphylococcus aureus exploits lipoic acid salvage to combat host oxidative stress
Summary: Phagocytic leukocytes employ reactive oxygen species to defend against pathogenic microorganisms. The bacterial pathogen Staphylococcus aureus adapts to oxidative stress by producing antioxidant enzymes and small molecules to protect proteins, nucleic acids, and other essential cellular com...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725008666 |
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| author | Iván C. Acosta Andrew Albers Liwei Fang Gustavo Serrato Wei Ping Teoh David G. Glanville Francis Alonzo, III |
| author_facet | Iván C. Acosta Andrew Albers Liwei Fang Gustavo Serrato Wei Ping Teoh David G. Glanville Francis Alonzo, III |
| author_sort | Iván C. Acosta |
| collection | DOAJ |
| description | Summary: Phagocytic leukocytes employ reactive oxygen species to defend against pathogenic microorganisms. The bacterial pathogen Staphylococcus aureus adapts to oxidative stress by producing antioxidant enzymes and small molecules to protect proteins, nucleic acids, and other essential cellular components. Here, we show that the lipoic acid carrier protein GcvH-L promotes S. aureus resistance to oxidative stress. The gene encoding GcvH-L lies within a conserved operon in several pathogenic microorganisms. The operon also encodes LplA2, a redox-responsive lipoyl ligase, and SirTM, an ADP-ribosyltransferase. We demonstrate that ADP-ribosylation of lipoyl-GcvH-L protects lipoic acid from oxidation and regulates its transfer from GcvH-L to enzyme complexes needed for central metabolism. A ΔgcvH-L mutant is attenuated during infection and is more sensitive to phagocyte respiratory burst, phenotypes that are abrogated in NADPH oxidase-deficient mice. Thus, ADP-ribosylation and lipoylation converge on GcvH-L to promote S. aureus resistance to oxidative stress. |
| format | Article |
| id | doaj-art-83ce02c721074338aeb5ea00ee61c12d |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-83ce02c721074338aeb5ea00ee61c12d2025-08-20T03:32:58ZengElsevierCell Reports2211-12472025-08-0144811609510.1016/j.celrep.2025.116095Staphylococcus aureus exploits lipoic acid salvage to combat host oxidative stressIván C. Acosta0Andrew Albers1Liwei Fang2Gustavo Serrato3Wei Ping Teoh4David G. Glanville5Francis Alonzo, III6Department of Microbiology and Immunology, University of Illinois at Chicago – College of Medicine, Chicago, IL, USADepartment of Microbiology and Immunology, University of Illinois at Chicago – College of Medicine, Chicago, IL, USADepartment of Microbiology and Immunology, University of Illinois at Chicago – College of Medicine, Chicago, IL, USADepartment of Microbiology and Immunology, University of Illinois at Chicago – College of Medicine, Chicago, IL, USA; Department of Microbiology and Immunology, Loyola University Chicago – Stritch School of Medicine, Maywood, IL, USADepartment of Microbiology and Immunology, Loyola University Chicago – Stritch School of Medicine, Maywood, IL, USADepartment of Microbiology and Immunology, Loyola University Chicago – Stritch School of Medicine, Maywood, IL, USADepartment of Microbiology and Immunology, University of Illinois at Chicago – College of Medicine, Chicago, IL, USA; Corresponding authorSummary: Phagocytic leukocytes employ reactive oxygen species to defend against pathogenic microorganisms. The bacterial pathogen Staphylococcus aureus adapts to oxidative stress by producing antioxidant enzymes and small molecules to protect proteins, nucleic acids, and other essential cellular components. Here, we show that the lipoic acid carrier protein GcvH-L promotes S. aureus resistance to oxidative stress. The gene encoding GcvH-L lies within a conserved operon in several pathogenic microorganisms. The operon also encodes LplA2, a redox-responsive lipoyl ligase, and SirTM, an ADP-ribosyltransferase. We demonstrate that ADP-ribosylation of lipoyl-GcvH-L protects lipoic acid from oxidation and regulates its transfer from GcvH-L to enzyme complexes needed for central metabolism. A ΔgcvH-L mutant is attenuated during infection and is more sensitive to phagocyte respiratory burst, phenotypes that are abrogated in NADPH oxidase-deficient mice. Thus, ADP-ribosylation and lipoylation converge on GcvH-L to promote S. aureus resistance to oxidative stress.http://www.sciencedirect.com/science/article/pii/S2211124725008666CP: MicrobiologyCP: Molecular biology |
| spellingShingle | Iván C. Acosta Andrew Albers Liwei Fang Gustavo Serrato Wei Ping Teoh David G. Glanville Francis Alonzo, III Staphylococcus aureus exploits lipoic acid salvage to combat host oxidative stress Cell Reports CP: Microbiology CP: Molecular biology |
| title | Staphylococcus aureus exploits lipoic acid salvage to combat host oxidative stress |
| title_full | Staphylococcus aureus exploits lipoic acid salvage to combat host oxidative stress |
| title_fullStr | Staphylococcus aureus exploits lipoic acid salvage to combat host oxidative stress |
| title_full_unstemmed | Staphylococcus aureus exploits lipoic acid salvage to combat host oxidative stress |
| title_short | Staphylococcus aureus exploits lipoic acid salvage to combat host oxidative stress |
| title_sort | staphylococcus aureus exploits lipoic acid salvage to combat host oxidative stress |
| topic | CP: Microbiology CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725008666 |
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