Identification of novel FosX family determinants from diverse environmental samples.

IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES
Nicolas Kieffer, Maria-Elisabeth Böhm, Fanny Berglund, Nachiket P Marathe, Michael R Gillings, D G Joakim Larsson
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引用次数: 0

Abstract

Objectives: This study aimed to identify novel fosfomycin resistance genes across diverse environmental samples, ranging in levels of anthropogenic pollution. We focused on fosfomycin resistance, and given its increasing clinical importance, explored the prevalence of these genes within different environmental contexts.

Methods: Metagenomic DNA was extracted from wastewater and sediment samples collected from sites in India, Sweden, and Antarctica. Class 1 integron gene cassette libraries were prepared, and resistant clones were selected on fosfomycin-supplemented media. Long-read sequencing was performed followed by bioinformatics analysis to identify novel fosfomycin resistance genes. The genes were cloned and functionally characterized in E. coli, and the impact of phosphonoformate on the enzymes was assessed.

Results: Four novel fosfomycin resistance genes were identified. Phylogenetic analysis placed these genes within the FosX family, a group of metalloenzymes that hydrolyse fosfomycin without thiol conjugation. The genes were subsequently renamed fosE2, fosI2, fosI3, and fosP. Functional assays confirmed that these genes conferred resistance to fosfomycin in E. coli, with MIC ranging from 32 μg/ml to 256 μg/ml. Unlike FosA/B enzymes, these FosX-like proteins were resistant to phosphonoformate inhibitory action. A fosI3 homolog was identified in Pseudomonas aeruginosa, highlighting potential clinical relevance.

Conclusions: This study expands the understanding of fosfomycin resistance by identifying new FosX family members across diverse environments. The lack of phosphonoformate inhibition underscores the clinical importance of these poorly studied enzymes, which warrant further investigation, particularly in pathogenic contexts.

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来源期刊
Journal of global antimicrobial resistance
Journal of global antimicrobial resistance INFECTIOUS DISEASES-PHARMACOLOGY & PHARMACY
CiteScore
8.70
自引率
2.20%
发文量
285
审稿时长
34 weeks
期刊介绍: The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes. JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR). Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.
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