One-year multicenter surveillance of Fosfomycin resistance Enterobacterales: the rise of FosA3-producing P. mirabilis
- David Ojcius
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Highlights
One-year multicenter survey of fosfomycin-resistant Enterobacterales in Czech Republic hospitals.
FosA3-producing Proteus mirabilis predominates.
FosA3-positive P. mirabilis ST185 forms a local clonal cluster while E. coli clones are heterogeneous.
Transporter defects (GlpT/UhpT) are widespread; most fosA strains carry ESBL genes.
Molecular surveillance is crucial to monitor and contain emerging fosfomycin resistance.
Abstract
The global rise of antimicrobial resistance has renewed interest in fosfomycin (FOS), an old antibiotic with activity against multidrug-resistant Enterobacterales. However, resistance to FOS is increasing, driven by impaired drug uptake, target modification, and by fosA-encoded enzymatic inactivation. This study assessed the prevalence and molecular basis of FOS resistance among Enterobacterales collected in Czech tertiary care hospitals in 2024. A total of 211 preliminary FOS-resistant isolates were obtained from nine hospitals across the Czech Republic, predominantly Proteus mirabilis (n=149) and Escherichia coli (n=57). All isolates showed elevated FOS MICs, and the PPF test identified FosA activity in 34/211 isolates. Carbon-source growth testing demonstrated widespread impairment of GlpT and UhpT transporters (93.8% affecting both). PCR confirmed fosA genes in 14 isolates (9 P. mirabilis, 5 E. coli). WGS revealed fosA3 as the dominant variant (85.7%), followed by fosA4 (14.3%). P. mirabilis isolates primarily belonged to ST185 and ST135, forming two Czech-specific fosA3 clusters with limited relatedness to international genomes. FosA-producing E. coli displayed broader diversity (ST69, ST58, ST550, ST1308). FosA4 was detected exclusively in E. coli. Most fosA-positive strains co-harbored ESBL genes, predominantly blaCTX-M-65. SNP-based phylogenies indicated local clonal circulation of fosA3-positive P. mirabilis ST185, whereas E. coli isolates showed heterogeneous international linkages. Analysis of GlpT/UhpT/MurA identified numerous amino acid substitutions, though only a minority were predicted to affect protein function. This study documents the first broader emergence of plasmid-mediated FOS resistance in Czech Enterobacterales and underscores the importance of continuous genomic surveillance of fosA-mediated resistance.
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