Acquisition And Loss Of Ctx-M Plasmids In Shigella Species Associated With Msm Transmission In The Uk

Shigellosis in men who have sex with men (MSM) is caused by multidrug resistant Shigellae, exhibiting resistance to anti-microbials including azithromycin, ciprofloxacin and more recently the third-generation cephalosporins. We sequenced four bla(CTX-M-27)-positive MSM Shigella isolates (2018-20) using Oxford Nanopore Technologies: three S. sonnei (identified as two MSM clade 2, one MSM clade 5) and one S. flexneri 3a, to explore AMR context. All S. sonnei isolates harboured Tn7/ Int2 chromosomal integrons, whereas S. flexneri 3a contained the Shigella Resistance Locus. All strains harboured IncFII pKSR100-like plasmids (67-83kbp); where present bla(CTX-M-27) was located on these plasmids flanked by IS26 and IS903B. however bla(CTX-M-27) was lost in S. flexneri 3a during storage between Illumina and Nanopore sequencing. IncFII AMR regions were mosaic and likely reorganised by IS26; three of the four plasmids contained azithromycin-resistance genes erm(B) and mph(A) and one harboured the pKSR100 integron. Additionally, all S. sonnei isolates possessed a large IncB/0/K/Z plasmid, two of which carried aph(3')-Ib/aph(6)-Id/sul2 and tet(A). Monitoring the transmission of mobile genetic elements with co-located AMR determinants is necessary to inform empirical treatment guidance and clinical management of MSM-associated shigellosis.