Recent Advances in Our Understanding of the Diversity and Roles of Chaperone-Usher Fimbriae in Facilitating Salmonella Host and Tissue Tropism

Abstract

Salmonella enterica is one of the most diverse and successful pathogens, representing a species with >2,600 serovars with a variety of adaptations that enable colonization and infection of a wide range of hosts. Fimbriae, thin hair-like projections that cover the surface of Salmonella, are thought to be the primary organelles that mediate Salmonella's interaction with, and adherence to, the host intestinal epithelium, representing an important step in the infection process. The recent expansion in genome sequencing efforts has enabled the discovery of novel fimbriae, thereby providing new perspectives on fimbrial diversity and distribution among a broad number of serovars. In this review, we provide an updated overview of the evolutionary events that shaped the Salmonella chaperone-usher fimbriome in light of recent phylogenetic studies describing the population structure of Salmonella enterica. Furthermore, we discuss the complexities of the chaperone-usher fimbriae-mediated host-pathogen interactions and the apparent redundant roles of chaperone-usher fimbriae in host and tissue tropism.

Keywords: Salmonella; adhesin Salmonella; chaperone-usher; fimbriae; host-pathogen interaction.

Figure 1

An overview of the Salmonella chaperone-usher fimbriome. (A) Structure of a chaperone-usher protein complex. The structure for Fim fimbria is shown as an example (PDB accession: 4J3O) (Geibel et al., 2013) to demonstrate the chaperone-usher biogenesis pathway. The membrane embedded usher (blue; FimD) accepts folded fimbrial subunits (FimF, FimG, and FimH) from the chaperone (orange; FimC) and translocates them across the outer membrane for elongation of the fimbria on the cell surface. (B) Overview of the distribution of known chaperone-usher fimbriae in Salmonella. Blue shading indicates the proportion of isolates in a given group that encoded the fimbrial gene cluster. White squares represent fimbrial gene clusters that were not included in analyses for a given Salmonella clade. The number of isolates included for each comparison varied: S. bongori (1–3 isolates), S. enterica subsp. arizonae and diarizonae (1–7 isolates), S. enterica subsp. houtenae (2–7 isolates), S. enterica subsp. salamae (2–9 isolates), S. enterica subsp. indica (1–3 isolates), and S. enterica subsp. enterica clades D (8 isolates), C (4 isolates), B (5–138 isolates), A1 (6–67 isolates), section Typhi (3–24 isolates), and A2 (10–186 isolates). For Tcf, Agf, Bcf, Fim, Lpf, Stg, Sth, Sti, Saf, Sef, Peg, Sta, Stb, Stc, Stk, Pef, Std, Ste, and Stf fimbriae, proportions of isolates in S. enterica subsp. enterica reflect only isolates from (Worley et al., 2018); for subsp. arizonae, diarizonae, houtenae, salamae, and indica datasets from multiple studies were compiled (Yue et al., 2012; Desai et al., 2013; Worley et al., 2018) as low numbers of isolates for these subspecies were reported. For S. bongori, data were compiled from (Fookes et al., 2011; Yue et al., 2012; Desai et al., 2013). Finally, for fimbriae Sdf, Sdg, Stj, Sdd/Smf, Sde, Mrk, Peh, Sba, Sdh, Sdi, Sdj, Fae, Sbc, Sbb, Sdk, Sdi, and Sdc, data were compiled from (Fookes et al., 2011; Yue et al., 2012; Desai et al., 2013). Fimbriae were considered as “present” if at least half of the genes in the operon were detected; pseudogenes were not considered in this analysis. In the Desai et al. (2013) dataset, Fae fimbria was referred to as “Skf” and Sdc fimbria was referred to as “Sas”. (C) A closer look at the distribution of chaperone-usher fimbriae among host-restricted (Gallinarum and Typhi), host-adapted (Choleraesuis and Dublin), and broad host range (Agona, Enteritidis, Newport, and Typhimurium) serovars. Background colors show associations with hosts (host generalists are shown in red to signify that they can infect all hosts shown, host-adapted/restricted serovars are aligned with the host that they are adapted/restricted to) (Hoelzer et al., 2011). Fimbriae are represented by the pie charts behind each Salmonella, with each slice of the chart representing an individual fimbria (clockwise from top light blue slice: Bcf, Fim, Lpf, Peg, Pef, Saf, Sef, Sta, Stb, Stc, Std, Ste, Stf, Stg, Sth, Sti, Stj, and Stk); slices appear colored in if the fimbria is present (i.e. white signifies absence of the fimbria) or have lines if (i) the fimbria is predicted to include hypothetically disrupted coding sequences for the gene encoding the usher protein or (ii) if more than half of the genes in the fimbrial gene cluster are predicted to be missing or are hypothetically disrupted coding sequences (Nuccio and Bäumler, 2014). Figure is based on data from (Nuccio and Bäumler, 2014) and reflects data for S. Agona SL483, S. Enteritidis P125109, S. Newport SL476, S. Typhi CT18, S. Typhimurium LT2, S. Gallinarum 287/91, S. Choleraesuis SC-B67, and S. Dublin CT_02021853.