Characterisation of a cointegrate plasmid harbouring bla_NDM-1 in a clinical Salmonella Lomita strain

This study aimed to characterise the molecular events underlying formation and evolution of a cointegrate plasmid harbouring bla_NDM-1 and bla_CMY-2 in a clinical Salmonella Lomita (S. Lomita) strain. The Salmonella strain SL131 was found to harbour two multidrug resistant (MDR) plasmids. One plasmid, pSL131_IncHI2, is a typical IncHI2 plasmid containing bla_OXA-1, catB3, arr-3, sul1, qnrB4 and bla_DHA-1 in a complex class 1 integron. The other plasmid, pSL131_IncA/C-IncX3, is a bla_NDM-1-bearing cointegrate plasmid consisting of IncX3 and IncA/C backbones, the formation of which is mediated by IS26. Stability assay showed that the cointegrate plasmid was highly stable in its natural host – S. Lomita – but would readily resolve into single plasmids upon conjugation, during which the IncX3 bla_NDM-1-bearing plasmid could be transferred to Escherichia coli strain EC600. Plasmid evolution through integration of two or more MDR plasmids would not only expand the resistance profile of the resultant plasmid, but also broaden the host spectrum of such resistance-encoding mobile elements. Better understanding of the underlying and triggering mechanisms of cointegration may facilitate development of intervention measures to curb formation and dissemination of such elements.