Abstract
Shigellosis in men who have sex with men (MSM) is caused by multidrug resistant Shigellae, exhibiting resistance to antimicrobials 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/O/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.
Highlights
Shigella is a Gram-negative genus comprising four species; Shigella dysenteriae, Shigella boydii, Shigella sonnei and Shigella flexneri, all etiological agents of shigellosis [1]
As few CTX-M plasmids have been described, we apply a combination of shortand long-read sequencing with Illumina and MinION technologies to assemble complete plasmids in four Shigella isolates associated with men who have sex with men (MSM) transmission in the United Kingdom to investigate the location of antimicrobial resistance (AMR) genes
We find blaCTX-M-27 is inserted into plasmids with high identity to known plasmids which have previously driven shigellosis epidemics worldwide and typically carry azithromycin resistance elements
Summary
Shigella is a Gram-negative genus comprising four species; Shigella dysenteriae, Shigella boydii, Shigella sonnei and Shigella flexneri, all etiological agents of shigellosis [1]. Shigellosis accounts for a significant proportion of the global diarrhoea burden; despite mortality decreases since the 1990s, ~125 m estimated cases occur annually, mainly in children
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