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

Abstract

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.

Figure 1

Scale diagram of WEK(I/M)xxFF (yellow) and WxxxE (red) domain containing effector proteins. Data for the alignment was generated from a Position Specific Iterated-BLAST search using SifA as the query, iterated five times. While SlrP and SspH1 are shown as possessing full WxxxE domains, it is noteworthy that they lack the actual WxxxE motif that is required to mimmick the function of Ras superfamily members. Similarly, SseI and SopD2 show similarity to WxxxE domains over only a short length of sequence as indicated, and this region does not include the WxxxE motif itself. Black lines represent sequence which is not similar to either WEK(I/M)xxFF or WxxxE domains, and arrowheads shown at the right end of a line indicate that the respective protein sequence extends beyond the space of the diagram.