Microevolution during the emergence of a monophasic Salmonella Typhimurium epidemic in the United Kingdom

Microevolutionary events associated with the emergence and clonal expansion of new 27 epidemic clones of bacterial pathogens hold the key to understanding the drivers of 28 epidemiological success. We describe a comparative whole genome sequence and 29 phylogenomic analysis of monophasic Salmonella Typhimurium isolates from the UK 30 and Italy from 2005-2012. Monophasic isolates from this time formed a single clade 31 distinct from recent monophasic epidemic clones described previously from North 32 America and Spain. The current UK monophasic epidemic clones encode a novel 33 genomic island encoding resistance to heavy metals (SGI-3), and composite transposon 34 encoding antibiotic resistance genes not present in other Typhimurium isolates, that 35 may have contributed to the epidemiological success. We also report a remarkable 36 degree of genotypic variation that accumulated during clonal expansion of a UK 37 epidemic including multiple independent acquisitions of a novel prophage carrying the 38 sopE gene and multiple deletion events affecting the phase II flagellin locus.