The Non-Flagellar Type III Secretion System Evolved from the Bacterial Flagellum and Diversified into Host-Cell Adapted Systems

Abstract

Type 3 secretion systems (T3SSs) are essential components of two complex bacterial machineries: the flagellum, which drives cell motility, and the non-flagellar T3SS (NF-T3SS), which delivers effectors into eukaryotic cells. Yet the origin, specialization, and diversification of these machineries remained unclear. We developed computational tools to identify homologous components of the two systems and to discriminate between them. Our analysis of >1,000 genomes identified 921 T3SSs, including 222 NF-T3SSs. Phylogenomic and comparative analyses of these systems argue that the NF-T3SS arose from an exaptation of the flagellum, i.e. the recruitment of part of the flagellum structure for the evolution of the new protein delivery function. This reconstructed chronology of the exaptation process proceeded in at least two steps. An intermediate ancestral form of NF-T3SS, whose descendants still exist in Myxococcales, lacked elements that are essential for motility and included a subset of NF-T3SS features. We argue that this ancestral version was involved in protein translocation. A second major step in the evolution of NF-T3SSs occurred via recruitment of secretins to the NF-T3SS, an event that occurred at least three times from different systems. In rhizobiales, a partial homologous gene replacement of the secretin resulted in two genes of complementary function. Acquisition of a secretin was followed by the rapid adaptation of the resulting NF-T3SSs to multiple, distinct eukaryotic cell envelopes where they became key in parasitic and mutualistic associations between prokaryotes and eukaryotes. Our work elucidates major steps of the evolutionary scenario leading to extant NF-T3SSs. It demonstrates how molecular evolution can convert one complex molecular machine into a second, equally complex machine by successive deletions, innovations, and recruitment from other molecular systems.

Type III secretion systems: the bacterial flagellum and the injectisome

“…They are distributed independently of the phylogeny of the respective species, and have probably been frequently transferred between species [38,55,60]. Latest analyses suggest that the ancestral T3SS was used for locomotion and was similar to current-day flagella, while modern injectisomes were derived through a series of gene losses and subsequent acquisitions via a non-flagellar ancestor that did not translocate proteins, leading to a protein translocation machinery [38] (figure 2). Within the injectisomes, eight subfamilies can be distinguished (table 2).…”

“…While, as mentioned above, there is no clear correlation between the phylogenetic tree of bacteria and their injectisome, injectisome subfamilies do confer host specificity. While the Ysc, SPI-1, SPI-2 and Chlamydia subfamilies target animal cells, Hrp1, Hrp2 and Rhizobia have plant host cells, and the more distantly related Myxococcus subfamily is present in free-living, non-pathogenic or symbiotic bacteria [12,38]. The Myxococcus subgroup lacks the secretin ring in the OM and any detectable needle subunit [38,56,61].…”

“…While the Ysc, SPI-1, SPI-2 and Chlamydia subfamilies target animal cells, Hrp1, Hrp2 and Rhizobia have plant host cells, and the more distantly related Myxococcus subfamily is present in free-living, non-pathogenic or symbiotic bacteria [12,38]. The Myxococcus subgroup lacks the secretin ring in the OM and any detectable needle subunit [38,56,61]. While it might form a fully functional T3SS by associating with a secretin of one of the type II secretion systems present in Myxococcus, it was also proposed to belong to an intermediate ancestral form of T3SS (figure 2) specialized in transport across the IM [38,61].…”

Structural Characterization at the Atomic Level of a Molecular Nano-Machine: The State of the Art of <i>Helicobacter Pylori</i> Flagellum Organization

“…It allows the assembly of the flagellum hook and of the filament beyond the membrane layer (Minamino and Macnab, 1999). It must be mentioned that flagellar systems and T3SS are evolutionary related each other (Abby and Rocha, 2012).…”

New Frontiers in Type III Secretion Biology: the Chlamydia Perspective

“…These observations led to an early hypothesis that the chlamydial T3S may represent the primordial system from which all others arose (2, 3). More detailed phylogenetic comparisons of T3SSs have led to a model where the NF-T3SS arose from flagella by loss of flagellar genes imparting a motility function (4). Additional genes were subsequently acquired and included those for an outer membrane secretin and secreted translocon.…”