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Arginine catabolism is essential to polymyxin dependence in Acinetobacter baumannii.
Han, Mei-Ling; Alsaadi, Yasser; Zhao, Jinxin; Zhu, Yan; Lu, Jing; Jiang, Xukai; Ma, Wendong; Patil, Nitin A; Dunstan, Rhys A; Le Brun, Anton P; Wickremasinghe, Hasini; Hu, Xiaohan; Wu, Yimin; Yu, Heidi H; Wang, Jiping; Barlow, Christopher K; Bergen, Phillip J; Shen, Hsin-Hui; Lithgow, Trevor; Creek, Darren J; Velkov, Tony; Li, Jian.
Afiliação
  • Han ML; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia. Electronic address: meiling.han@monash.edu.
  • Alsaadi Y; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Zhao J; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Zhu Y; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Lu J; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Jiang X; National Glycoengineering Research Centre, Shandong University, Qingdao 266237, China.
  • Ma W; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Patil NA; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Dunstan RA; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Le Brun AP; Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2232, Australia.
  • Wickremasinghe H; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Hu X; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Wu Y; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Yu HH; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Wang J; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Barlow CK; Monash Proteomics and Metabolomics Facility, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
  • Bergen PJ; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Shen HH; Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Clayton, VIC 3800, Australia.
  • Lithgow T; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
  • Creek DJ; Monash Proteomics and Metabolomics Facility, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
  • Velkov T; Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
  • Li J; Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia. Electronic address: jian.li@monash.edu.
Cell Rep ; 43(7): 114410, 2024 Jul 23.
Article em En | MEDLINE | ID: mdl-38923457
ABSTRACT
Polymyxins are often the only effective antibiotics against the "Critical" pathogen Acinetobacter baumannii. Worryingly, highly polymyxin-resistant A. baumannii displaying dependence on polymyxins has emerged in the clinic, leading to diagnosis and treatment failures. Here, we report that arginine metabolism is essential for polymyxin-dependent A. baumannii. Specifically, the arginine degradation pathway was significantly altered in polymyxin-dependent strains compared to wild-type strains, with critical metabolites (e.g., L-arginine and L-glutamate) severely depleted and expression of the astABCDE operon significantly increased. Supplementation of arginine increased bacterial metabolic activity and suppressed polymyxin dependence. Deletion of astA, the first gene in the arginine degradation pathway, decreased phosphatidylglycerol and increased phosphatidylethanolamine levels in the outer membrane, thereby reducing the interaction with polymyxins. This study elucidates the molecular mechanism by which arginine metabolism impacts polymyxin dependence in A. baumannii, underscoring its critical role in improving diagnosis and treatment of life-threatening infections caused by "undetectable" polymyxin-dependent A. baumannii.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article