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Nosocomial Bacteria Inhibition with Polymyxin B: In Silico Gene Mining and In Vitro Analysis.
Chunduru, Jayendra; LaRoe, Nicholas; Garza, Jeremy; Hamood, Abdul N; Paré, Paul W.
Affiliation
  • Chunduru J; Chemistry & Biochemistry Department, Texas Tech University, Lubbock, TX 79409, USA.
  • LaRoe N; Chemistry & Biochemistry Department, Texas Tech University, Lubbock, TX 79409, USA.
  • Garza J; Department of Immunology & Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Hamood AN; Department of Immunology & Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Paré PW; Chemistry & Biochemistry Department, Texas Tech University, Lubbock, TX 79409, USA.
Antibiotics (Basel) ; 13(8)2024 Aug 08.
Article in En | MEDLINE | ID: mdl-39200045
ABSTRACT
Multidrug-resistant bacteria present a significant public health challenge; such pathogens exhibit reduced susceptibility to conventional antibiotics, limiting current treatment options. Cationic non-ribosomal peptides (CNRPs) such as brevicidine and polymyxins have emerged as promising candidates to block Gram-negative bacteria. To investigate the capability of bacteria to biosynthesize CNRPs, and specifically polymyxins, over 11,000 bacterial genomes were mined in silico. Paenibacillus polymyxa was identified as having a robust biosynthetic capacity, based on multiple polymyxin gene clusters. P. polymyxa biosynthetic competence was confirmed by metabolite characterization via HPLC purification and MALDI TOF/TOF analysis. When grown in a selected medium, the metabolite yield was 4 mg/L with a 20-fold specific activity increase. Polymyxin B (PMB) was assayed with select nosocomial pathogens, including Pseudomonas aeruginosa, Klebsiella pneumonia, and Acinetobacter baumaii, which exhibited minimum inhibitory concentrations of 4, 1, and 1 µg/mL, respectively.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Antibiotics (Basel) Year: 2024 Document type: Article Affiliation country: United States Country of publication: Switzerland

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Antibiotics (Basel) Year: 2024 Document type: Article Affiliation country: United States Country of publication: Switzerland