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. 2021 May 12:12:660094.
doi: 10.3389/fmicb.2021.660094. eCollection 2021.

OXA-484, an OXA-48-Type Carbapenem-Hydrolyzing Class D β-Lactamase From Escherichia coli

Julian Sommer  1 , Kristina M Gerbracht  1 , Felix F Krause  1 , Florian Wild  1 , Manuela Tietgen  1   2   3 , Sara Riedel-Christ  1 , Janko Sattler  4 , Axel Hamprecht  4   5 , Volkhard A J Kempf  1   3 , Stephan Göttig  1
Affiliations

OXA-484, an OXA-48-Type Carbapenem-Hydrolyzing Class D β-Lactamase From Escherichia coli

Julian Sommer et al. Front Microbiol. .

Abstract

OXA-48-like carbapenemases are among the most frequent carbapenemases in Gram-negative Enterobacterales worldwide with the highest prevalence in the Middle East, North Africa and Europe. Here, we investigated the so far uncharacterized carbapenemase OXA-484 from a clinical E. coli isolate belonging to the high-risk clone ST410 regarding antibiotic resistance pattern, horizontal gene transfer (HGT) and genetic support. OXA-484 differs by the amino acid substitution 214G compared to the most closely related variants OXA-181 (214R) and OXA-232 (214S). The bla OXA - 484 was carried on a self-transmissible 51.5 kb IncX3 plasmid (pOXA-484) showing high sequence similarity with plasmids harboring bla OXA - 181. Intraspecies and intergenus HGT of pOXA-484 to different recipients occurred at low frequencies of 1.4 × 10-7 to 2.1 × 10-6. OXA-484 increased MICs of temocillin and carbapenems similar to OXA-232 and OXA-244, but lower compared with OXA-48 and OXA-181. Hence, OXA-484 combines properties of OXA-181-like plasmid support and transferability as well as β-lactamase activity of OXA-232.

Keywords: Enterobacterales; IncX; OXA-48; OXA-484; beta-lactamases; carbapenemases; plasmid.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Plasmid map of pOXA-484 harboring blaOXA–484. Colored arrows indicate antibiotic resistance genes blaOXA–484 (dark red) and qnrS1 (light red), insertion elements (yellow), disrupted genes (gray), replication, partitioning, plasmid stabilization, and transfer genes of the IncX3 plasmid backbone (green) and hypothetical proteins (light blue). The IncX3 plasmid backbone is marked in purple. GC content is represented by the inner green line and AT content by the inner blue line.
FIGURE 2
FIGURE 2
Genetic environment of blaOXA–484, blaOXA–181, and blaOXA–232 within pOXA-484_EC-JS316, pOXA-181_EC-2800, and pOXA-232_KP-4814. Colored arrows indicate insertion elements (yellow), fragmented genes (gray), antibiotic resistance genes (red) and genes of the plasmid backbone (green). Shaded regions between the plasmids share >99% nucleotide sequence identity.
FIGURE 3
FIGURE 3
Transconjugation frequencies during horizontal transfer of plasmids harboring blaOXA–484, blaOXA–181, and blaOXA–48 from E. coli and K. pneumoniae clinical isolates to E. coli J53 and K. quasipneumoniae subsp. quasipneumoniae PRZ. Each dot represents the frequency of a single transconjugation experiment, whereas the bars indicate the mean of all experiments. ***P < 0.0001 (Mann-Whitney U test). Transconjugation frequencies to (A) E. coli J53 and (B) K. quasipneumoniae subsp. quasipneumoniae PRZ.
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