Abstract

Background: Bacteroides fragilis shows high antimicrobial resistance (AMR) rates and possesses numerous AMR mechanisms. Its carbapenem-resistant strains (metallo-β-lactamase cfiA-positive) appear as an emergent, evolving clade. Methods: This work examines the genomes, taxonomy, and phylogenetic relationships with respect to other B. fragilis genomes of two B. fragilis strains (CNM20180471 and CNM20200206) resistant to meropenem+EDTA and other antimicrobial agents. Results: Both strains possessed cfiA genes (cfiA14b and the new cfiA28), along with other AMR mechanisms. The presence of other efflux-pump genes, mexAB/mexJK/mexXY-oprM, acrEF/mdtEF-tolC, and especially cusR, which reduces the entry of carbapenem via the repression of porin OprD, may be related to meropenem–EDTA resistance. None of the detected insertion sequences were located upstream of cfiA. The genomes of these and other B. fragilis strains that clustered together in phylogenetic analyses did not meet the condition of >95% average nucleotide/amino acid identity, or >70% in silico genome-to-genome hybridization similarity, to be deemed members of the same species, although <1% difference in the genomic G+C content was seen with respect to the reference genome B. fragilis NCTC 9343T. Conclusions: Carbapenem-resistant strains may be considered a distinct clonal entity, and their surveillance is recommended given the ease with which they appear to acquire AMR.

Highlights

  • Bacteroides fragilis is a common bacterium of the human gut

  • Antimicrobial resistance surveys have reported on B. fragilis populations to show high resistance to penicillins, cephalosporins, and tetracyclines; medium resistance (5–35%) to β-lactam/β-lactamase inhibitor combinations, cephamycins, macrolidelincosamide-streptogramin B (MLSB) drugs and fluoroquinolones; and low resistance (

  • B. fragilis CNM20180471 and CNM20200206 strains were initially identified by MALDITOF/MS as B. fragilis with a score of 2.11 and 2.38, respectively

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Summary

Introduction

Bacteroides fragilis is a common bacterium of the human gut. It generally behaves as a commensal species, but under certain conditions it can cause severe intra-abdominal infections, skin and soft tissue infections, brain abscesses, surgical site infections, and anaerobic bacteraemia [1]. The main antimicrobial resistance (AMR) determinants involved are cepA for penicillins and cephalosporins, cfxA for cephamycins, cfiA for carbapenems, ermF for MLSB compounds, nimA–J for metronidazole, tetQ for tetracyclines, and gyrA point mutations and bexA/B (coding for efflux pumps) for fluoroquinolones [4,8,9,10]. Some of these traits are commonly encoded by chromosomal genes carried on integrative and conjugative elements (ICEs), including conjugative transposons (CTns), compound transposons, and mobilizable plasmids [2,3,9,10,11,12]. Conclusions: Carbapenem-resistant strains may be considered a distinct clonal entity, and their surveillance is recommended given the ease with which they appear to acquire AMR

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