Single-cell sequencing provides clues about the host interactions of segmented filamentous bacteria (SFB) - PubMed (original) (raw)

Figure 6.

Proposed life cycle of segmented filamentous bacteria (SFB) in the murine intestine, and putative targets of SFB ADP-ribosyltransferases (ADPRTs). This schematic is based on the present genome sequence study, previous microscopy studies (e.g., Davis and Savage 1974; Chase and Erlandsen 1976; Koopman et al. 1987; Klaasen et al. 1992), and other SFB-related literature. (A) Migration of SFB through the mucus layer may be facilitated by chemotaxis/flagella-driven motility, and degradation of mucin by excreted alpha-_N_-acetylglucosaminidase. Attachment of holdfast cell to intestinal epithelial cell in the small intestine. Flagellin may be recognized by host determinants, trigger immune responses, and protect epithelial cells from apoptosis. SFB may obtain essential nutrients from the host and import them using a variety of transport systems. (B–D) Undifferentiated filaments; (E,F) differentiated filaments. (C–F) Filaments may be protected from phagocytosis by host cells due to their size. (B) Growth of holdfast segment cell. (C) Early stage of filament development. Anchored holdfast segment, formation of primary segment cell, and secondary segments via new transverse septa. (D) Filament growth through division of segment cells. At various stages during the life cycle, fermentation products and extracellular enzymes may be released. Released products may also be used by other microorganisms, such as “epibionts” of unknown affiliation that have been observed to be associated with SFB. (E) Initiation of differentiation of reproductive cells. Scissions and cell-shape modulation processes may be facilitated by dynamin. Tertiary traverse septum formation, and production of spherical cells, that subsequently form C-shaped cells. Differentiation of one C-shaped cell into two holdfast cells. Phage production may occur at certain stages during the SFB life cycle. (F) Differentiation of holdfasts and spores. Formation of holdfasts with condensed nuclei, and release into the environment, likely facilitated by the action of autolysins. Nonreleased holdfasts can differentiate further into spores. Two holdfasts develop into one spore. Precipitation of cortex and spore coat material around holdfasts as plaques. The size of the holdfasts decrease and they are drawn together. Cortex and spore coat increase in thickness. Release of spores, facilitated by autolysins. (G–I) Released progeny may be dispersed within the same host as well as transmitted to new hosts. Migration of holdfasts may be facilitated by flagella-driven motility and chemotaxis. (J) Induction of germination cascade in spores within the host through unknown signal (possibly, bile). (1–5) Potential targets of ADP-ribosylation by SFB ADPRT. (1) Regulation of phage production through modulation of bacterial RNA polymerase activity. (2) Modification of G-actin, and inhibition of actin polymerization. (3) ADP-ribosylation of T-cell surface proteins, and modulation of T-cell homeostasis. (4) ADP-ribosylation of defensins, and modulation of their activity. (5) ADP-ribosylation of G protein in dendritic cells, leading to up-regulation of cAMP production, and secretion of effector molecules that induce Th17 cells. (Blue circle) Essential nutrients, e.g., amino acids, vitamins, co-factors, sugars. (Gray circle) Fermentation products, such as lactate, acetate, ethanol, H2, CO2. (Red asterisk) Myosin-cross-reactive antigen (MCRA). (Gray box with arrow) Transporters for import and export of small molecules, e.g., MATE-efflux, ABC-transporters, PTS system, ion transporters. (Green circle) Extracellular and surface-located enzymes, such as proteases, bile acid hydrolase (choloylglycine hydrolase), collagenase, alpha-_N_-acetyl-glucosaminidase, fibronectin binding protein. (Red circle) Autolysin (_N_-acetylmuramoyl-L-alanine amidase). (Yellow circle) Dynamin. (Orange circle) SFB ADP-ribosyltransferase. (Gray oval) Surface modifications, such as _O_-acetylation, and polysaccharide deacetylation. (Yellow cross) Catalase. (Orange cross) Ruberythrin. (Red star) Antimicrobials, such as NO, antimicrobial peptides, lysozyme. (Gray irregular shape) Polysaccharide.