Modified Intracellular-Associated Phenotypes in a Recombinant Salmonella Typhi Expressing S. Typhimurium SPI-3 Sequences

Abstract

A bioinformatics comparison of Salmonella Pathogenicity Island 3 sequences from S. Typhi and S. Typhimurium serovars showed that ten genes are highly conserved. However three of them are pseudogenes in S. Typhi. Our aim was to understand what functions are lost in S. Typhi due to pseudogenes by constructing a S. Typhi genetic hybrid carrying the SPI-3 region of S. Typhimurium instead of its own SPI-3. We observed that under stressful conditions the hybrid strain showed a clear impairment in resistance to hydrogen peroxide and decreased survival within U937 culture monocytes. We hypothesized that the marT-fidL operon, encoded in SPI-3, was responsible for the new phenotypes because marT is a pseudogen in S. Typhi and has a demonstrated role as a transcriptional regulator in S. Typhimurium. Therefore we cloned and transferred the S. Typhimurium marT-fidL operon into S. Typhi and confirmed that invasion of monocytes was dramatically decreased. Finally, our findings suggest that the genomic and functional differences between SPI-3 sequences have implications in the host specificity of Typhi and Typhimurium serovars.

Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis

“…Typhi with the SPI3 genes (with unknown functions) from S . Typhimurium dramatically reduced the invasion of monocytes [51]. Comparative genomics also reveals repeated loss of metabolic pathways in some species.…”

“…Missing metabolic pathways in genomes from pathogens has also been dismissed as the result of lack of selection due to the nutrient-rich environment in the host. However, new data suggest that this loss might be advantageous for virulence [50, 51]. Future studies could focus on those bacterial metabolic genes possibly involved in host-pathogen interactions.…”

Helicobacter and Salmonella Persistent Infection Strategies

“…The molecular bases for S. Typhi's host restriction and unique pathogenic attributes are just beginning to be understood, but they are believed to be the result of a combination of genome degradation and the acquisition of new genetic information (Retamal et al 2010;Sabbagh et al 2010;Trombert et al 2011;Spano and Galan 2012;Song et al 2013). For example, the proteolytic targeting of a host GTPase, Rab29, by an effector protein, GtgE, that is present in S. Typhimurium and not S. Typhi distinguishes the intracellular compartments of human-adapted Typhi and the broad-host S. Typhimurium (Spano and Galan 2012).…”

“…For example, the proteolytic targeting of a host GTPase, Rab29, by an effector protein, GtgE, that is present in S. Typhimurium and not S. Typhi distinguishes the intracellular compartments of human-adapted Typhi and the broad-host S. Typhimurium (Spano and Galan 2012). Several functional studies indicate that S. Typhi pseudogenes contribute to its adaptation to humans (Retamal et al 2010;Trombert et al 2011). Perhaps the role of sseI is similar.…”

A review of the ecology, colonization and genetic characterization of Salmonella enterica serovar Sofia, a prolific but avirulent poultry serovar in Australia

“…It is suggested that mutations within these genes in S. Sofia may render them unable to fulfill their role within the T3SS of SPI-2 although analysis of their functionality should be undertaken. SPI-3 contains 10 genes that encode proteins whose functions have not all been experimentally characterized (Retamal, Castillo-Ruiz, Villagra, Morgado, & Mora, 2010). Of these five genes were considered to have changes that may affect protein function (Gan et al, in press).…”