Whole genome sequencing provides insights into the genetic determinants of invasiveness in Salmonella Dublin

Abstract

Salmonella enterica subsp. enterica serovar Dublin (S. Dublin) is one of the non-typhoidal Salmonella (NTS); however, a relatively high proportion of human infections are associated with invasive disease. We applied whole genome sequencing to representative invasive and non-invasive clinical isolates of S. Dublin to determine the genomic variations among them and to investigate the underlying genetic determinants associated with invasiveness in S. Dublin. Although no particular genomic variation was found to differentiate in invasive and non-invasive isolates four virulence factors were detected within the genome of all isolates including two different type VI secretion systems (T6SS) encoded on two Salmonella pathogenicity islands (SPI), including SPI-6 (T6SSSPI-6) and SPI-19 (T6SSSPI-19), an intact lambdoid prophage (Gifsy-2-like prophage) that contributes significantly to the virulence and pathogenesis of Salmonella serotypes in addition to a virulence plasmid. These four virulence factors may all contribute to the potential of S. Dublin to cause invasive disease in humans.

Keywords: Comparative genomics; Salmonella Dublin; invasiveness.

Fig. 1.

Phylogenetic tree of Salmonella Dublin isolates based on single nucleotide polymorphisms determined from whole genome sequence. Invasive isolates (highlighted in light blue) and faecal isolates (highlighted in yellow) are intermixed. The generalized time-reversible model of nucleotide substitution for each position was used.

Fig. 2.

Complete genome alignment of different Salmonella serovars (including the draft genome of representatives of clinical Irish isolates of S. Dublin sequenced in this study) generated using BRIG [27]. S. Dublin strain CT_02021853 genome is used as a reference. The gene cluster of SPI-6 T6SS (gene range SeD_A0289–SeD_A0326) is also included in the alignment. The genome of clinical S. Dublin isolates (including invasive and gastroenteritis isolates) and other invasive serovars including S. Choleraesuis, S. Typhimurium, S. Typhi and S. Paratyphi A harbours SPI-6 T6SS while it is absent from S. Enteritidis.

Fig. 3.

Complete genome alignment of different Salmonella serovars (including the draft genome of representatives of clinical Irish isolates of S. Dublin sequenced in this study) generated using BRIG [27]. S. Dublin strain CT_02021853 genome is used as a reference. The gene cluster of SPI-19 T6SS (gene range SeD_A1212–SeD_A1243) is also included in the alignment. The genome of S. Dublin clinical isolates (including invasive and gastroenteritis isolates), S. Agona and the poultry-adapted serovars including S. Gallinarum and S. Pullorum harbours SPI-19T6SS while it is absent from S. Enteritidis.

Fig. 4.

Complete genome alignment of different Salmonella serovars (including the draft genome of representatives of clinical Irish isolates of S. Dublin sequenced in this study) generated using BRIG [27]. S. Dublin strain CT_02021853 genome is used as a reference. Prophage Gifsy-2 genome is also included in the alignment. The genome of clinical S. Dublin isolates (including invasive and gastroenteritis isolates), S. Typhimurium and S. Newport harbours Gifsy-2 prophage while Gifsy-2 is defective in S. Enteritidis PT4.