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In Staphylococcus aureus, the acyl-CoA synthetase MbcS supports branched-chain fatty acid synthesis from carboxylic acid and aldehyde precursors.
Dos Santos Ferreira, Marcelle C; Pendleton, Augustus; Yeo, Won-Sik; Málaga Gadea, Fabiana C; Camelo, Danna; McGuire, Maeve; Brinsmade, Shaun R.
Afiliación
  • Dos Santos Ferreira MC; Department of Biology, Georgetown University, Washington, District of Columbia, USA.
  • Pendleton A; Department of Biology, Georgetown University, Washington, District of Columbia, USA.
  • Yeo WS; Department of Biology, Georgetown University, Washington, District of Columbia, USA.
  • Málaga Gadea FC; Department of Biology, Georgetown University, Washington, District of Columbia, USA.
  • Camelo D; Department of Biology, Georgetown University, Washington, District of Columbia, USA.
  • McGuire M; Department of Biology, Georgetown University, Washington, District of Columbia, USA.
  • Brinsmade SR; Department of Biology, Georgetown University, Washington, District of Columbia, USA.
Mol Microbiol ; 121(5): 865-881, 2024 05.
Article en En | MEDLINE | ID: mdl-38366323
ABSTRACT
In the human pathogen Staphylococcus aureus, branched-chain fatty acids (BCFAs) are the most abundant fatty acids in membrane phospholipids. Strains deficient for BCFAs synthesis experience auxotrophy in laboratory culture and attenuated virulence during infection. Furthermore, the membrane of S. aureus is among the main targets for antibiotic therapy. Therefore, determining the mechanisms involved in BCFAs synthesis is critical to manage S. aureus infections. Here, we report that the overexpression of SAUSA300_2542 (annotated to encode an acyl-CoA synthetase) restores BCFAs synthesis in strains lacking the canonical biosynthetic pathway catalyzed by the branched-chain α-keto acid dehydrogenase (BKDH) complex. We demonstrate that the acyl-CoA synthetase activity of MbcS activates branched-chain carboxylic acids (BCCAs), and is required by S. aureus to utilize the isoleucine derivative 2-methylbutyraldehyde to restore BCFAs synthesis in S. aureus. Based on the ability of some staphylococci to convert branched-chain aldehydes into their respective BCCAs and our findings demonstrating that branched-chain aldehydes are in fact BCFAs precursors, we propose that MbcS promotes the scavenging of exogenous BCCAs and mediates BCFA synthesis via a de novo alternative pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Staphylococcus aureus / Coenzima A Ligasas / Ácidos Grasos Idioma: En Revista: Mol Microbiol Asunto de la revista: BIOLOGIA MOLECULAR / MICROBIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Staphylococcus aureus / Coenzima A Ligasas / Ácidos Grasos Idioma: En Revista: Mol Microbiol Asunto de la revista: BIOLOGIA MOLECULAR / MICROBIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido