Rapid Increase of CTX-M-Producing Shigella sonnei Isolates in Switzerland: Spread of Common Plasmids and International Clones

The Swiss Centre for Antibiotic Resistance (ANRESIS) has recently noted an increase of extended-spectrum cephalosporin-resistant (ESC-R) S. sonnei isolates nationwide (3.8% in 2016 vs. 37.5% in 2019). To understand this phenomenon, we analyzed 25 representative isolates (of which 14 ESC-R) collected in Switzerland during 2016-2019. Whole-genome sequencing was achieved using both Illumina and Nanopore platforms. Both ESC-R and susceptible isolates belonged to ST152. The ESC-R isolates carried blaCTX-M-3 in IncI1-pST57 (n=5), blaCTX-M-15 in IncFII (F2:A-:B-) (n=5), blaCTX-M-15 in IncI1-pST16, and blaCTX-M-27, blaCTX-M-55, or blaCTX-M-134 in other IncFII plasmids (n=1 each). Plasmids having the same bla and Inc group exhibited high genetic identity to each other, but also to plasmids previously reported in other Enterobacterales. Core-genome analysis showed that there were 4 main clusters, each of which included strains that differed by <58 SNVs, both blaCTX-M-positive and blaCTX-M-negative isolates. Moreover, most isolates belonging to the same cluster shared an identical cgST. For instance, cluster-1 included 4 isolates of cgST113036, of which only 3 harbored the IncI1-pST57 blaCTX-M-3-positive plasmid. The 25 S. sonnei isolates were also subjected to phylogenetic comparison with deposited international strains. As a result, matching isolates (same cgST and differing by <8 SNVs) have been reported in the UK, USA, France, and the Netherlands. Overall, our results suggest that some common S. sonnei clusters can spread between continents and can be imported into other nations after international trips. Such clusters include, in part, isolates that do not possess blaESBL-harboring plasmids, indicating their tendency to acquire them from other Enterobacterales.