Johnson R, Byrne A, Berger CN, Klemm E, Crepin VF, Dougan G, Frankel G
Salmonella enterica serovars causes gastroenteritis or typhoid fever in humans, with virulence depending on the action of two type III secretion systems (SPI-1 and SPI-2). SptP is a Salmonella SPI-1 effector, involved in mediating recovery of the host cytoskeleton post-infection. SptP requires a chaperone, SicP, for stability and secretion. SptP has 94% identity between S Typhimurium and S Typhi; direct comparison of the protein sequences revealed that S Typhi SptP has numerous amino acid changes within its chaperone-binding domain. Subsequent comparison of ΔsptP S Typhi and S Typhimurium strains demonstrated that unlike S Typhimurium, SptP in S Typhi was not involved in invasion or cytoskeletal recovery post-infection. Investigating if the observed amino acid changes within SptP of S Typhi affected its function revealed that S Typhi SptP was unable to complement S. Typhimurium ΔsptP due to an absence of secretion. We further demonstrated that whilst S Typhimurium SptP is stable intracellularly within S Typhi, S Typhi SptP is unstable, although stability could be recovered following replacement of the chaperone-binding domain with that of S Typhimurium. Direct assessment of the strength of interaction between SptP and SicP of both serovars via bacterial two hybrid demonstrated that S Typhi SptP has a significantly weaker interaction with SicP than the equivalent proteins in S Typhimurium. Taken together our results suggest that changes within the chaperone-binding domain of SptP in S Typhi hinder binding to its chaperone, resulting in instability and preventing translocation, and therefore restricting the intracellular activity of this effector.
Studies investigating Salmonella pathogenesis typically rely on Salmonella Typhimurium, despite Salmonella Typhi causing the more severe disease in humans. As such, an understanding of S. Typhi pathogenesis is lacking. Differences within the type III secretion system effector, SptP, between typhoidal and non-typhoidal serovars led us to characterise this effector within S Typhi. Our results suggest that SptP is not translocated from typhoidal serovars, despite loss of sptP resulting in virulence defects in S Typhimurium. Although SptP is just one effector, our results exemplify that the behaviour of these serovars are significantly different, and genes identified as important for S. Typhimurium virulence may not translate to S Typhi.
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