Clonal/subclonal changes and accumulation of CTX-M-type β-lactamase genes in fluoroquinolone-resistant Escherichia coli ST131 and ST1193 strains isolated during the past 12 years, Japan

ABSTRACT: Objectives: Fluoroquinolone (FQ)- and third-generation cephalosporin-resistant Escherichia coli are increasing in Japan. In the early 2000s, the FQ-resistant E. coli clone ST131 increased in clinical settings worldwide. It frequently produces extended-spectrum β-lactamases (ESBLs) such as CTX-M. This study aimed to explore the characteristics of FQ-resistant E. coli isolated in Japan during 2008–2009 and 2020. Methods: We compared FQ-resistant E. coli clinical isolates from urine samples collected in 2020 (151 isolates) with a FQ-resistant E. coli collection isolated in 2008–2009 (42 isolates). Identification of E. coli ST131 clades and blaCTX-M were determined by multiplex PCR. Sequence types of non-ST131 isolates were determined by whole-genome sequencing. Results: Although the prevalence of ST131 was comparable in 2020 (74.2%) and 2008–2009 (78.6%), the subclades differed during the two time periods (C1-nM27: 40.2% in 2008–2009 vs. 78.8% in 2020; C1-M27: 32.1% in 2008–2009 vs. 9.1% in 2020). The incidence of blaCTX-M among ST131 isolates increased from 27.3% in 2008–2009 to 64.3% in 2020. blaCTX-M was found in 80.6% and 93.8% of C1-M27 and C2 in 2020, respectively, and blaCTX-M possession in C1-nM27 increased from 19.2% in 2008–2009 to 40% in 2020. FQ-resistant ST1193 was detected only in 2020 (17.9% of 151 isolates, of which 14.8% possessed blaCTX-M). Conclusion: Increased resistance of E. coli to FQs and third-generation cephalosporins in Japan can be attributed to the accumulation of blaCTX-M in C1-nM27 and the increase of C1-M27 and C2 clades with high blaCTX-M possession, alongside the spread of ST1193.