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Region Hovedstaden - en del af Københavns Universitetshospital

The Soil Microbiota Harbors a Diversity of Carbapenem-Hydrolyzing ß-Lactamases of Potential Clinical Relevance

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The origin of carbapenem-hydrolyzing metallo-ß-lactamases (MBLs) acquired by clinical bacteria is largely unknown. We investigated frequency, host range, diversity and functionality of MBLs in the soil microbiota. Twenty-five soil samples of different type and geographical origin were analyzed by antimicrobial selective culture followed by phenotypic testing and expression of MBL-encoding genes in Escherichia coli, and whole genome sequencing of MBL-producing strains was performed. Carbapenemase activity was detected in 29 bacterial isolates from 13 soil samples, leading to identification of seven new MBLs in presumptive Pedobacter roseus (PEDO-1), Pedobacter borealis (PEDO-2), Pedobacter kyungheensis (PEDO-3), Chryseobacterium piscium (CPS-1), Epilithonimonas tenax (ESP-1), Massilia oculi (MSI-1) and Sphingomonas sp. (SPG-1). Carbapenemase production was likely an intrinsic feature in Chryseobacterium and Epilithonimonas as it occurred in reference strains of different species within these genera. The amino acid identity to MBLs described in clinical bacteria ranged between 40 and 69%. Remarkable features of the new MBLs included prophage integration of the encoding gene (PEDO-1), an unusual amino acid residue at a key position for MBL structure and catalysis (CPS-1), and overlap with putative OXA ß-lactamase (MSI-1). Heterologous expression of PEDO-1, CPS-1 and ESP-1in E. coli increased significantly the MICs of ampicillin, ceftazidime, cefpodoxime, cefoxitin and meropenem. Our study shows that MBL producers are widespread in soil and include four genera that were previously not known to produce MBLs. The MBLs produced by these bacteria are distantly related to MBLs identified in clinical samples but constitute resistance determinants of clinical relevance if acquired by pathogenic bacteria.

TidsskriftAntimicrobial Agents and Chemotherapy
Sider (fra-til)151-160
Antal sider9
StatusUdgivet - 19 okt. 2015

ID: 45716884