Abstract
We isolated and characterized a carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical strain from blood carrying a novel blaOXA gene, blaOXA–926, and belonging to ST29, an uncommon CRKP type. The strain, 130002, was genome sequenced using both short- and long-read sequencing and has a 94.9-kb self-transmissible IncFII plasmid carrying blaKPC–2. K. pneumoniae genomes of the ST29 complex (ST29 and its single-allele variants) were retrieved and were subjected to single nucleotide polymorphism-based phylogenomic analysis. A total of 157 genomes of the ST29 complex were identified. This complex is commonly associated with extended-spectrum β-lactamase-encoding genes, in particular, blaCTX–M–15 but rarely has carbapenemase genes. The novel plasmid-encoded β-lactamase-encoding gene blaOXA–926 was identified on a 117.8-kb IncFIA-IncFII plasmid, which was transferrable in the presence of the blaKPC–2-carrying plasmid. blaOXA–926 was cloned and MICs of β-lactams in the transformants were determined using microdilution. OXA-926 has a narrow spectrum conferring reduced susceptibility only to piperacillin, piperacillin-tazobactam, and cephalothin. Avibactam cannot fully inhibit OXA-926. blaOXA–926 and its variants have been seen in Klebsiella strains in Asia and Brazil. OXA-926 is the closest in sequence identity (89.9%) to a chromosome-encoding OXA-type enzyme of Variovorax guangxiensis. In conclusion, OXA-926 is novel plasmid-borne narrow-spectrum β-lactamase that cannot be fully inhibited by avibactam. It is likely that blaOXA–926 originates from a species closely related to V. guangxiensis and was introduced into Klebsiella > 10 years ago.
Highlights
Resistance to β-lactam agents such as penicillins, cephalosporins, and carbapenems in the Enterobacteriaceae, one of the most common human pathogens, is mainly due to the production of hydrolyzing enzymes called β-lactamases. β-Lactamases can be divided into classes A, B, C, and D based on amino acid homology (Hall and Barlow, 2005)
Strain 130002 was resistant to aztreonam, ceftazidime, cefepime, ertapenem, imipenem, meropenem, and piperacillin-tazobactam but was susceptible to ceftazidime-avibactam and was intermediate to colistin (Table 2)
As ST29 is an uncommon type of carbapenem-resistant Klebsiella pneumoniae (CRKP), we retrieved all genomes of K. pneumoniae belonging to the ST29 complex including ST29 and its single-allele variants (ST193, 465, 711, 723, 985, 1161, and 1271) from GenBank
Summary
Resistance to β-lactam agents such as penicillins, cephalosporins, and carbapenems in the Enterobacteriaceae, one of the most common human pathogens, is mainly due to the production of hydrolyzing enzymes called β-lactamases. β-Lactamases can be divided into classes A, B, C, and D based on amino acid homology (Hall and Barlow, 2005). Resistance to β-lactam agents such as penicillins, cephalosporins, and carbapenems in the Enterobacteriaceae, one of the most common human pathogens, is mainly due to the production of hydrolyzing enzymes called β-lactamases. OXA (oxacillinase) is a large group of class D β-lactamases with a remarkably varied spectrum against β-lactam agents from narrow-spectrum (hydrolyzing penicillins only, e.g., OXA-1) to extended-spectrum (with ability to hydrolyze 3rd generation cephalosporins, e.g., OXA-11) and carbapenemases (e.g., OXA23 and OXA-48) (Evans and Amyes, 2014). We found a blaOXA gene encoding a novel OXA enzyme in a carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical strain and determined its active spectrum. We analyzed all available genomes of ST29 and found that this ST is commonly associated with the carriage of extended-spectrum β-lactamase-encoding genes rather than carbapenemases genes
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