دورية أكاديمية
Comparative metabolomics revealed key pathways associated with the synergistic killing of multidrug-resistant Klebsiella pneumoniae by a bacteriophage-polymyxin combination.
العنوان: | Comparative metabolomics revealed key pathways associated with the synergistic killing of multidrug-resistant Klebsiella pneumoniae by a bacteriophage-polymyxin combination. |
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المؤلفون: | Han ML; Biomedicine Discovery Institute, Infection and Immunity Program, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia., Nang SC; Biomedicine Discovery Institute, Infection and Immunity Program, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia., Lin YW; Biomedicine Discovery Institute, Infection and Immunity Program, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia., Zhu Y; Biomedicine Discovery Institute, Infection and Immunity Program, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia., Yu HH; Biomedicine Discovery Institute, Infection and Immunity Program, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia., Wickremasinghe H; Biomedicine Discovery Institute, Infection and Immunity Program, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia., Barlow CK; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.; Monash Proteomics and Metabolomics Facility, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia., Creek DJ; Monash Proteomics and Metabolomics Facility, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia., Crawford S; Ramaciotti Centre for Cryo Electron Microscopy, Monash University, Australia., Rao G; Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA., Dai C; Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, China., Barr JJ; School of Biological Sciences, Monash University, 25 Rainforest Walk, Clayton, Victoria 3800, Australia., Chan K; Advanced Drug Delivery Group, School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia., Turner Schooley R; Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, CA, USA., Velkov T; Department of Pharmacology & Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia., Li J; Biomedicine Discovery Institute, Infection and Immunity Program, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia. |
المصدر: | Computational and structural biotechnology journal [Comput Struct Biotechnol J] 2022 Jan 06; Vol. 20, pp. 485-495. Date of Electronic Publication: 2022 Jan 06 (Print Publication: 2022). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology Country of Publication: Netherlands NLM ID: 101585369 Publication Model: eCollection Cited Medium: Print ISSN: 2001-0370 (Print) Linking ISSN: 20010370 NLM ISO Abbreviation: Comput Struct Biotechnol J Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Publication: Amsterdam : Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology Original Publication: Gothenburg, Sweden : Research Network of Computational and Structural Biotechnology |
مستخلص: | Resistance to the last-line polymyxins is emerging in multidrug-resistant Klebsiella pneumoniae and phage therapy is a promising alternative. However, phage monotherapy often rapidly causes resistance and few studies have examined antibiotic-phage combinations against K. pneumoniae . Here, we investigated the combination of polymyxin B with a novel phage pK8 against an mcr -1-carrying polymyxin-resistant clinical isolate Kp II-503 (polymyxin B MIC, 8 mg/L). The phage genome was sequenced and bacterial metabolomes were analysed at 4 and 24 h following the treatment with polymyxin B (16 mg/L), phage pK8 (10 2 PFU/mL) and their combination. Minimal metabolic changes across 24 h were observed with polymyxin B alone; whereas a significant inhibition of the citrate cycle, pentose phosphate pathway, amino acid and nucleotide metabolism occurred with the phage-polymyxin combination at both 4 and 24 h, but with phage alone only at 4 h. The development of resistance to phage alone was associated with enhanced membrane lipid and decreased amino acid biosynthesis in Kp II-503. Notably, cAMP, cGMP and cCMP were significantly enriched (3.1-6.6 log Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.) |
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معلومات مُعتمدة: | R21 AI156766 United States AI NIAID NIH HHS |
فهرسة مساهمة: | Keywords: Bacteriophage; Central carbon metabolism; Klebsiella pneumoniae; Metabolome; Polymyxin resistance |
تواريخ الأحداث: | Date Created: 20220124 Latest Revision: 20220716 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC8760530 |
DOI: | 10.1016/j.csbj.2021.12.039 |
PMID: | 35070170 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2001-0370 |
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DOI: | 10.1016/j.csbj.2021.12.039 |