Comparison Of Genome Sequence And Pathogenicity Between Salmonella Serovars

Salmonella are important human and animal pathogens.Taxonomically, Salmonella organisms are considered as a single species,known as Salmonella enterica,which includes more than 2,500 different serovars.Different serovars have distinct host range and clinical performance.While most serovars,e.g.,Typhimurium, are host-generalists and can cause self-limited gastroenteritis in human,a few serovars,including Typhi and Paratyphi A,are specifically adapted to human and can elicit typhoid fever,a serious systemic infection with high mortality rates.A few serovars,such as Choleraesuis,are most adapted to single animal species and only occasionally infect humans.To date,complete genome sequences of several serovars have been available in public database,but two core issues in the filed of Salmonella research,i.e.,the genetic basis of host range and typhoid pathogenicity,remain unknown.To better elucidate the two issues,three individual studies that compared different serovars were carried out in this doctoral dissertation.The first study reported the genome sequence of serovar Paratyphi C and compared it with that of other typhoid and non-typhoid serovars.Paratyphi C is another human-adapted typhoid serovar but belongs to serogroup C as well as Choleraesuis.Through comparison of the whole genome sequence,we found that Paratyphi C is highly related to Choleraesuis other than Typhi and Paratyphi A, demonstrating the separate ancestries and evolutionary convergence of these human-adapted typhoid agents.The pseudogene composition also showed how Paratyphi C lost unnecessary functions convergently with Typhi and Paratyphi A and divergently from Choleraesuis,revealing a potential selection pressure produced during the bacteria adapted to their respective host.We did not found any genes exclusively present in human typhoidal strains.Thus typhoid-related genes may exist in many serovars,yet the host range restricts their functions within human body.The second study described Salmonella virulence plasmid with respect to their transmission mode.Only eight serovars except Typhi and Paratyphi A are known to harbor virulence plasmid,thus the virulence plasmid is not prerequisite to typhoid fever.Partial or entire deletion of tra operon made the virulence plasmid lose the capability of lateral transmission.The sequence divergence of virulence plasmid between serovars is congruent with that of chormosome,also suggesting the vertical transmission mode.The serovar Dublin houses two virulence plasmids of different size:pSDVr and pSDVu.Sequence analysis showed that pSDVr was a recombinant product of pSDVu and a conjugative plasmid pOU1114.More important is that pSDVr has gained a weak conjugative ability after recombination.The last study analyzed the interaction between Salmonella and amoebae. Amoebae is a type of protozoan commonly found in soil,aquatic systems and even within animal intestines,and feeds mainly on bacteria and fungi by phagocytosis. However,Salmonella are able to survive and replicate in an amoebic intracellular environment and therefore can escape from the predation.Our experiment showed that the number of intracellular bacteria increased at 6 hour post-infection,and the viability of amoebae was significantly reduced at 24 hour post-infection.DNA ladder was not identified in amoebic cell death,indicating an apoptosis-like cell death in Salmonella-infected amoebae.Strains from three serovars,i.e.,Typhimurium,Typhi and Choleraesuis,were used in the experiment,and no difference was observed in terms of their growth within amoebae over time.