Global clonal spread of mcr-3-carrying MDR ST34 Salmonella enterica serotype Typhimurium and monophasic 1,4,[5],12:i:− variants from clinical isolates

Abstract

Objectives To investigate the prevalence and transmission of mcr-3 among Salmonella enterica serotype Typhimurium and 1,4,[5],12:i:−. Methods A total of 4724 clinical Salmonella isolates were screened for the presence of mcr-3 in China during 2014–19. The clonal relationship of the mcr-3-positive isolates and their plasmid contents and complete sequence were also characterized based on WGS data from the Illumina and MinION platforms. Results We identified 10 mcr-3-positive isolates, and all were MDR, mostly resistant to colistin, cefotaxime, ciprofloxacin, doxycycline and florfenicol. mcr-3 was co-present with blaCTX-M-55-qnrS1 on hybrid ST3-IncC-FII conjugatable plasmids (n = 6) and an ST3-IncC non-conjugatable plasmid (n = 1) and embedded into a pCHL5009T-like IncFII plasmid on the Salmonella chromosome (n = 3). Four distinctive genetic contexts surrounded mcr-3 and all but one were closely related to each other and to the corresponding region of IncFII plasmid pCHL5009T. IS15DI was most likely the vehicle for integration of mcr-3-carrying IncFII plasmids into ST3-IncC plasmids and the chromosome and for shaping the MDR regions. In addition, a phylogenetic tree based on the core genome revealed a unique Salmonella lineage (≤665 SNPs) that contained these 10 mcr-3-positive isolates and another 38 (33 from patients) mcr-3-positive Salmonella from five countries. In particular, most of the 51 mcr-3-positive isolates belonged to ST34 and harboured diverse antibiotic resistance genes (ARGs), including mcr-3-blaCTX-M-55-qnrS1, and possessed similar ARG profiles. Conclusions Our findings revealed global clonal spread of MDR ST34 Salmonella from clinical isolates co-harbouring mcr-3 with blaCTX-M-55 and qnrS1 and a flexibility of mcr-3 co-transmittance with other ARGs mediated by mobile genetic elements.

Occurrence of mcr-mediated colistin resistance in Salmonella clinical isolates in Thailand

“…Thus, it should be noted that the mcr gene, especially mcr-3.1 , has already spread in Thailand since at least 2007, the earliest isolation time point of the mcr -harbouring isolates among our collection of Salmonella clinical isolates. Currently, the mcr-3 gene has become more widespread and prevalent in Salmonella , S. Typhimurium, and a monophasic variant of S. Typhimurium in particular 21 , 24 , 25 . The clonal spread of the MDR ST34 S. Typhimurium (including monophasic variants) was observed in China during 2014–2019, during which time the global distribution was confirmed by the high similarity between the genomes of mcr-3 -harboring Salmonella isolated from across four continents 25 .…”

“…Currently, the mcr-3 gene has become more widespread and prevalent in Salmonella , S. Typhimurium, and a monophasic variant of S. Typhimurium in particular 21 , 24 , 25 . The clonal spread of the MDR ST34 S. Typhimurium (including monophasic variants) was observed in China during 2014–2019, during which time the global distribution was confirmed by the high similarity between the genomes of mcr-3 -harboring Salmonella isolated from across four continents 25 . Interestingly, most patients with mcr-3 -positive Salmonella infections from Denmark, Canada, USA, and Australia had a travel history to Thailand, Vietnam, or China, during 2013–2016 25 .…”

“…Moreover, we found some AMR plasmids supporting the dissemination of the mcr-3 gene among diverse genetic backgrounds, including the IncA/C, IncHI2, IncFII, and IncA/C-IncFIIs plasmids. These plasmids have been described in E. coli and in few serotypes of Salmonella that have mostly been recovered from food animal isolates 25 . Remarkably, two distinct monophasic variants of S. Typhimurium isolates carried the mcr-1.9 gene on IncX4 plasmids with an identical size of 33 kb.…”

Plasmid-borne colistin resistance gene mcr-1 in a multidrug resistant Salmonella enterica serovar Typhimurium isolate from an infant with acute diarrhea in China

“…For example, the ASSuT tetra-(ampicillin, streptomycin, sulfonamides, and tetracycline) and ACSSuT (ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline) penta-resistant patterns are the most commonly reported (Mellor et al, 2019;Thung et al, 2016;Wang et al, 2019). Salmonella 4, [5],12:i:-, a monophasic variant of Salmonella Typhimurium, progressively became an emerging multidrug resistant clade carrying plasmid-mediated resistance genes (Elnekave et al, 2018;Mourao et al, 2014) and the sequence types mostly are ST19 and ST34 (Elnekave et al, 2018;Pernille Gymoese et al, 2017;Sun et al, 2020). The antimicrobial resistance (AMR) of Salmonella has become a matter of concern worldwide.…”

Plasmid Dynamics of mcr-1-Positive Salmonella spp. in a General Hospital in China

“…After Salmonella species carrying mcr-1 were detected in the United Kingdom in 2016, the level of occurrence of mcr-1 in Salmonella among livestock and humans, but also the environment, is increasing worldwide (Cui et al, 2017;Yi et al, 2017b). In addition, although another five mcr variants (mcr-2, mcr-3, mcr-4, mcr-5, and mcr-9) have been identified in Salmonella species (Carattoli et al, 2018;Garcia-Graells et al, 2018;Borowiak et al, 2019;Carroll et al, 2019;Sun et al, 2020), mcr-1 is still the most common mcr gene found in COL-resistant Salmonella spp. (Borowiak et al, 2020).…”