Title : Non-typhoidal Salmonella: Why Should We Care?
Non-typhoidal Salmonella (NTS) Dublin has adapted to cause invasive illness in humans. There is no vaccine against iNTS and disease management is further complicated by the emergence of multidrug resistant (MDR) strains. It is estimated that invasive non-typhoidal Salmonella (iNTS) serovars cause over 680,000 human deaths per year. We apply next generation sequencing (NGS) technologies and associated bioinformatics analyses tools to understand the genetic basis of iNTS Dublin.
Whole genome sequencing (WGS) of human S. Dublin strains revealed several virulence factors and mobile genetic elements (MGEs) that may contribute to bacterial virulence and enable the bacteria to cause invasive disease in humans including Gifsy-2 prophage, virulence plasmid and Salmonella pathogenicity islands; SPI-7 harbouring the Vi antigen, SPI-6 and SPI-19 harbouring two different T6SSs and the novel pathogenicity island ST313-GI. Understanding the genetic basis of virulence of iNTS Dublin will provide insights into developing novel therapeutics and effective vaccine against human infection.
Interestingly, NTS have developed MDR against current antibiotics including the last resort; colistin (polymexins). Bacteriophage therapy is therefore the hope for treatment of MDR bacterial infections however one of the key limitations to therapeutic use of phages, is the limited host range of many phages and the ease of development of bacterial resistance to phages. A solution is to develop one or a cocktail of engineered phage that overcome these limitations. An essential step towards this goal is understanding the complex dynamics of bacteria-phage interaction. We therefore use Anderson phage typing scheme as a valuable model system for study of phage-host interaction to characterize all bacterial antiviral systems (including clustered regularly interspaced short palindromic repeat (CRISPRs) loci and CRISPR-associated (Cas) proteins (CRISPR-Cas) immune systems, superinfection exclusion (Sie) and restriction-modification (R-M) systems) as well as phage evasion strategies (including anti-CRISPR). Understanding the dynamics of bacteria-phage interaction will provide new insights into phage biology and strategies for genetic modification of phages and designing effective broad spectrum engineered phages to overcome the limitations of bacteriophages as therapeutic agents.