Study of plasmidal transmissions of mcr-1 in a large tertiary hospital in the Netherlands. Intrapatient interspecific transmission of mcr-1-carrying plasmid and other plasmidal transmission cases

Background. The global spread of colistin resistance poses a healthcare threat. However, the epidemiology of mcr-1-carrying-plasmids in a local healthcare setting is largely unknown. In this study, we aim to characterize plasmids and their transmission in mcr-1 positive isolates identified from a large hospital in the Netherlands.Methods. We retrospectively included all clinical mcr-1-carrying isolates from patients hospitalized in years 2010-2018. In principle, extracted plasmids from mcr-1 positive isolates were sequenced using a combination of short (iSeq) and long (MinION) reads chemistries. The plasmid hybrid assemblies had their incompatibility type (Inc type) and genetic background characterized. A comparison was performed of the detected plasmids with all public available mcr-1-carrying-plasmids. Results. We confirmed the presence of the mcr-1 in 22 isolates, derived from 14 patients. We identified 21 plasmids, which were described with incompatibility type of IncX4, IncI2, IncHI2 and double Inc types; IncHI2/IncN and IncHI2/IncQ. Additionally, the mcr-1 was identified in the chromosome of a prevalent strain of K. pneumoniae (ST147). Genomic analysis of available mcr-1-carrying-plasmids indicated plasmidal transmission in the hospital through patients and species. Conclusion. In a small collection of isolates, we observed multiple plasmidal transmission cases such as intrapatient-interspecific and among patients hospitalized in different years. Mcr-1 plasmids have a diverse genetic background which can corelate with the Inc type. Plasmid enrichment, and genetic background in all available plasmids contributed in defining transmissions. Understanding the transmission of mcr-1-carrying plasmids, the spread of the mcr-1 gene can be observed, studied and hopefully limited in a local tertiary care center and eventually globally.