Potential origins and horizontal transfer of type III secretion systems and effectors

A major virulence mechanism used by pathogenic Gram-negative bacteria is the delivery of effector proteins from the bacterial cytoplasm into host cells by type III secretion. Typically, genes encoding type III secretion systems (T3SS) and effectors have been horizontally acquired by the bacteria that employ them. In proteobacteria, and especially Salmonella, and attaching and effacing (A/E) pathogens, the genetic structure of these systems presents as a large locus encoding a T3SS with a small number of effectors, plus numerous small unlinked loci encoding additional individual effectors. We discuss the generation of novel effectors, and the evolution of G+C content following acquisition. We also consider the currently held view that each locus has been acquired individually, as well as propose an alternative where recombination may have redistributed and broken up clusters of effectors. It is clear that the evolution of this virulence strategy is highly complex and challenging to analyze.