Detection of a new Extended-Spectrum β-Lactamase (ESBL) Family: SED-2 in Citrobacter sedlakii
2Sackler Faculty of Medicine, Tel Aviv University, Israel
Extended-spectrum β-lactamases (ESBLs) are class A beta lactamases that can hydrolyze broad spectrum cephalosporins, penicilins, and monobactams. They are the leading acquired resistance mechanism to these classes and are the main mechanism responsible to worldwide resistance among Enterobacterales. The ESBL genes are often carried on genetic transferable elements, which can spread between clones and species. Here we report on a new family of ESBL arising from SED-1 a class A narrow spectrum beta-lactamase (which does not confer resistance to broad-spectrum cephalosporins), reported previously in Citrobacter sedlakii.
We detected a C. sedlakii isolate resistant to broad spectrum cephalosporins, with positive phenotypic test for carbapenem hydrolysis and performed whole genome sequencing. We identified a new variant of blaSed-1 which differs by 6 nucleotide resulting in one amino acid substitution (uncharged Glutamine residue with a positively charged Argenine), and named this enzyme SED-2. Sed-2 gene was cloned into E. coli and the transformant strain, acquired resistance to first, second, and third generation cephalosporins. This activity was not inhibited by clavulanic acid and tazobactam, but was inhibited by avibactam. Interestingly, despite not conferring resistance to carbapenems, the mCIM test was positive. Growth analysis revealed that growth was not inhibited by broad spectrum cephalosporins, and was inhibited by carbapenems only after 4 hours of growth.
Sed-2 shows characteristics of an inhibitor-resistant ESBL, thus belongs to the 2br group. The detection of a new family of ESBL, which is inhibitor resistant is worrisome as it may spread and add to the overall burden of antimicrobial resistance.