Salmonella paratyphi C: Genetic Divergence from Salmonella choleraesuis and Pathogenic Convergence with Salmonella typhi

Abstract

BackgroundAlthough over 1400 Salmonella serovars cause usually self-limited gastroenteritis in humans, a few, e.g., Salmonella typhi and S. paratyphi C, cause typhoid, a potentially fatal systemic infection. It is not known whether the typhoid agents have evolved from a common ancestor (by divergent processes) or acquired similar pathogenic traits independently (by convergent processes). Comparison of different typhoid agents with non-typhoidal Salmonella lineages will provide excellent models for studies on how similar pathogens might have evolved.Methodologies/Principal FindingsWe sequenced a strain of S. paratyphi C, RKS4594, and compared it with previously sequenced Salmonella strains. RKS4594 contains a chromosome of 4,833,080 bp and a plasmid of 55,414 bp. We predicted 4,640 intact coding sequences (4,578 in the chromosome and 62 in the plasmid) and 152 pseudogenes (149 in the chromosome and 3 in the plasmid). RKS4594 shares as many as 4346 of the 4,640 genes with a strain of S. choleraesuis, which is primarily a swine pathogen, but only 4008 genes with another human-adapted typhoid agent, S. typhi. Comparison of 3691 genes shared by all six sequenced Salmonella strains placed S. paratyphi C and S. choleraesuis together at one end, and S. typhi at the opposite end, of the phylogenetic tree, demonstrating separate ancestries of the human-adapted typhoid agents. S. paratyphi C seemed to have suffered enormous selection pressures during its adaptation to man as suggested by the differential nucleotide substitutions and different sets of pseudogenes, between S. paratyphi C and S. choleraesuis.Conclusions S. paratyphi C does not share a common ancestor with other human-adapted typhoid agents, supporting the convergent evolution model of the typhoid agents. S. paratyphi C has diverged from a common ancestor with S. choleraesuis by accumulating genomic novelty during adaptation to man.

Host Specificity of Bacterial Pathogens

“…For example, the shdA and misL genes encode nonfimbrial adhesins that enhance intestinal colonization of S. Typhimurium (Kingsley et al 2000Dorsey et al 2005). Pseudogene formation in host-restricted Salmonella serovars has inactivated both shdA (S. Typhi, S. Paratyphi A, S. Paratyphi C, S. Dublin, and S. Gallinarum) and misL (S. Typhi) McClelland et al 2004;Thomson et al 2008;Liu et al 2009;Betancor et al 2012). Another group of intestinal colonization factors of S. Typhimurium is encoded by fimbrial operons of the chaperone usher assembly class .…”

“…Tetrathionate respiration supports growth of S. Typhimurium on ethanolamine as a carbon source in the gut lumen during gastroenteritis (Thiennimitr et al 2011). This pathway is degraded in specialists S. Paratyphi C (eutA, eutC, eutK, and eutN) and S. Choleraesuis (eutN) (Liu et al 2009). Growth on ethanolamine under anaerobic conditions necessitates biosynthesis of vitamin B12 by the cob/cbi gene cluster (Roof and Roth 1988), which contains pseudogenes in S. Typhi (cbiM, cbiK, cbiJ, and cbiC), S. Paratyphi A (cbiA), and S. Gallinarum (cobD, cbiD, and cbiC) McClelland et al 2004;Thomson et al 2008).…”

Microfluidic Chip-Based Detection and Intraspecies Strain Discrimination of Salmonella Serovars Derived from Whole Blood of Septic Mice

“…enterica serovars Typhimurium and Choleraesuis. These two serovars, the causative agents of enterocolitis and sepsis in humans, respectively, are quite closely related (homologous genes of Salmonella serovars have over 97% DNA sequence identity) and thus serve as a particularly challenging test of the specificity of our platform (41,(53)(54)(55)(56)(57)(58); reviewed in reference 59). LAMP of Salmonella-specific sequences.…”

The 3Cs provide a novel concept of bacterial species: messages from the genome as illustrated by Salmonella

“…One point that is especially worth emphasizing is that, at higher resolution, physical mapping reveals a genome structure that is common to all strains of the same lineage but entirely different from all those of other lineagesthere is no gradual drop in similarity with increasing genetic distances among the bacteria. The distinctness in genome structure is absolute even for Salmonella lineages that are as closely related as between S. paratyphi C and S. choleraesuis (Liu et al 2009;Chiu et al 2005) or between S. pullorum and S. gallinarum (Liu et al 2002;Wu et al 2005). These findings indicate that individual Salmonella lineages, resolved by serotyping or physical mapping, are genetically isolated without free flows of genes between them.…”

“…However, a common antigenic formula may be shared by several distinct Salmonella species, such as 1,9,12:-:-by Salmonella pullorum and Salmonella gallinarum, or 1,4,[5],12: b:1,2 by Salmonella paratyphi B and Salmonella java. All Salmonella species are closely related as revealed first by DNA-DNA re-association assays (Crosa et al 1973), and later by physical mapping (Liu et al 1999) and genomic sequencing (Parkhill et al 2001;McClelland et al 2001;Deng et al 2003;McClelland et al 2004;Chiu et al 2005;Liu et al 2009). As a result, in the 1980s, some people united all Salmonella species into just one or two species, Salmonella enterica and Salmonella bongori, and all the previous Salmonella species became serovars of S. enterica or S. bongori (Reeves et al 1989;Popoff et al 2004).…”