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Serine deamination by human serine racemase synergizes with antibiotics to curtail the replication of Chlamydia trachomatis.
Mott, Patricia D; Zea, Arnold H; Lewis, Jamiya; Mirzalieva, Oygul; Aiyar, Ashok A.
Afiliación
  • Mott PD; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. Electronic address: pdehon@lsuhsc.edu.
  • Zea AH; Department of Microbiology, Immunology, & Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
  • Lewis J; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
  • Mirzalieva O; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
  • Aiyar AA; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. Electronic address: aaiyar@lsuhsc.edu.
J Biol Chem ; 300(6): 107350, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38718865
ABSTRACT
The obligate intracellular bacterium, Chlamydia trachomatis, has evolved to depend on its human host for many metabolites, including most amino acids and three of the four nucleotides. Given this, it is not surprising that depletion of a single amino acid in the host cell growth medium blocks chlamydial replication. Paradoxically, supra-normal levels of some amino acids also block productive replication of Chlamydia. Here, we have determined how elevated serine levels, generated by exogenous supplementation, impede chlamydial inclusion development and reduce the generation of infectious progeny. Our findings reveal that human serine racemase, which is broadly expressed in multiple tissues, potentiates the anti-chlamydial effect of elevated serine concentrations. In addition to reversibly converting l-serine to d-serine, serine racemase also deaminates serine via ß-elimination. We have determined that d-serine does not directly impact Chlamydia; rather, ammonia generated by serine deamination limits the productive chlamydial replication. Our findings imply that ammonia produced within host cells can traverse the chlamydial inclusion membrane. Further, this property of serine deaminase can be exploited to sensitize Chlamydia to concentrations of doxycycline that are otherwise not bactericidal. Because exogenously elevated levels of serine can be tolerated over extended periods, the broad expression pattern of serine racemase indicates it to be a host enzyme whose activity can be directed against multiple intracellular bacterial pathogens. From a therapeutic perspective, demonstrating host metabolism can be skewed to generate an anti-bacterial metabolite that synergizes with antibiotics, we believe our results provide a new approach to target intracellular pathogens.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Serina / Chlamydia trachomatis / Antibacterianos Límite: Humans Idioma: En Revista: J Biol Chem Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
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: Serina / Chlamydia trachomatis / Antibacterianos Límite: Humans Idioma: En Revista: J Biol Chem Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos