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

Dereje Dadi Gudeta, Valeria Bortolaia, Greg Amos, Elizabeth M. H. Wellington, Kristian Koefoed Brandt, Laurent Poirel, Jesper Boye Nielsen, Henrik Westh, Luca Guardabassi

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Abstract

The origin of carbapenem-hydrolyzing metallo-beta-lactamases (MBLs) acquired by clinical bacteria is largely unknown. We investigated the frequency, host range, diversity, and functionality of MBLs in the soil microbiota. Twenty-five soil samples of different types and geographical origins 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 a putative OXA beta-lactamase (MSI-1). Heterologous expression of PEDO-1, CPS-1, and ESP-1in E. coli significantly increased 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.
Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number1
Pages (from-to)151-160
Number of pages10
ISSN0066-4804
DOIs
Publication statusPublished - 2016
Externally publishedYes

Keywords

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases
  • amino acid
  • ampicillin
  • beta lactamase
  • carbapenem
  • carbapenemase
  • cefazolin
  • cefepime
  • cefotaxime
  • cefoxitin
  • cefpodoxime
  • ceftazidime
  • ceftriaxone
  • clavulanic acid
  • meropenem
  • metallo beta lactamase
  • piperacillin plus tazobactam
  • antibiotic resistance
  • Article
  • bacterial strain
  • bacterium isolate
  • catalysis
  • Chryseobacterium
  • Chryseobacterium balustinum
  • Chryseobacterium piscium
  • Chryseobacterium scophthalmum
  • enzyme activity
  • enzyme structure
  • enzyme synthesis
  • Epilithonimonas lactis
  • Epilithonimonas tenax
  • Escherichia coli
  • gene frequency
  • gene sequence
  • genetic variability
  • Gram negative bacterium
  • heterologous expression
  • host range
  • Janthinobacterium
  • Janthinobacterium lividum
  • Massilia oculi
  • Massilia timonae
  • minimum inhibitory concentration
  • nonhuman
  • nucleotide sequence
  • Pedobacter
  • Pedobacter africanus
  • Pedobacter agri
  • Pedobacter borealis
  • Pedobacter boryungensis
  • Pedobacter heparinus
  • Pedobacter kyungheensis
  • Pedobacter roseus
  • Pedobacter saltans
  • phenotype
  • priority journal
  • prophage
  • soil microflora
  • Sphingomonas
  • Sphingomonas adhaesiva
  • Sphingomonas aquatilis
  • Sphingomonas echinoides
  • Sphingomonas hankookensis
  • Sphingomonas jaspsi
  • Sphingomonas maltophilia
  • Sphingomonas paucimobilis
  • Amino Acid Sequence
  • Anti-Bacterial Agents
  • Carbapenems
  • Cloning, Molecular
  • Europe
  • Gene Expression
  • Hydrolysis
  • Molecular Sequence Data
  • Recombinant Proteins
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Soil Microbiology
  • beta-Lactam Resistance
  • beta-Lactamases
  • Mechanisms of Resistance
  • MICROBIOLOGY
  • PHARMACOLOGY
  • PSEUDOMONAS-AERUGINOSA
  • BIOCHEMICAL-CHARACTERIZATION
  • ANTIBIOTIC-RESISTANCE
  • 3-DIMENSIONAL STRUCTURE
  • RAPID DETECTION
  • ENTEROBACTERIACEAE
  • BACTERIA
  • ISOLATE
  • RESISTOME
  • INTEGRON
  • Genetics - General
  • Biochemistry studies - General
  • Biochemistry studies - Proteins, peptides and amino acids
  • Pathology - Therapy
  • Pharmacology - General
  • Physiology and biochemistry of bacteria
  • Genetics of bacteria and viruses
  • Chemotherapy - General, methods and metabolism
  • Chemotherapy - Antibacterial agents
  • metallo-beta-lactamase
  • Bacteria, Eubacteria, Microorganisms
  • Microorganisms
  • species diversity
  • GenBank sequence data

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