What does the flagellar sheath do?

A flagellum is an essential tool for any aspiring pathogen, with functions beyond mere locomotion. They are potent virulence factors, as seen in pathogens of vertebrates. Unfortunately, the difficulty in separating motility from other microbe-host interaction effects in this group has obscured any other purposes the flagellum may serve.

Though highly conserved in basic molecular structure, the bacterial flagellum is very adventurous when it comes to morphology, number and extra bits. A prominent additional feature is the flagellar sheath, present in many symbiotic groups have this membrane.

The function of this sheath is sheathed in mystery, but is posited to hide the flagellum from the host’s immune system. However there are two arguments against this idea. First of all, the flagellar sheath is made of lipopolysaccharide (LPS) which also triggers immune responses. Secondly, it is not known what the rapid spinning of the flagellum would do to the flagellar sheath; surely the membrane would fly off as small, immune-stimulatory vesicles? Both arguments hint that the flagellar sheath is involved in modifying or even encouraging host immune responses, rather than avoiding them.

To delve into this case, the beloved model symbiosis between the Hawaiian bobtail squid Euprymna scolopes and the radiant Vibrio fischeri was utilised. The initiation of this symbiosis was tracked in real time to identify any roles of the flagellar sheath in host-microbe interactions. Non-rotating flagellum mutants were compared with the wild type to observe the effect on ciliated epithelial apoptosis (CEA, see my previous blog post for more detail).

The flagellar sheath was confirmed to be involved in modulating host immune responses. The rotation of a sheathed flagellum was revealed to release LPS, inducing an immune response in the squid. LPS was shown to be a key initiator of the apoptotic tissue development in E. scolopes, indicating the role of the flagellar sheath in a specific recognition role in this symbiosis. Non-rotating mutants released less LPS and were much less successful in inducing CEA development, suggesting that the host had narrow LPS thresholds required for symbiosis development, adding a new layer of specificity to this host-microbe interaction.

Understanding the purpose of the flagellar sheath is limited by knowledge of how lipids behave. For example, how does LPS interact with the immune system? What kind of cellular receptors bind to lipids? Does LPS form vesicles, which may contain other molecules like flagellin (the main protein in flagella) and do they have a synergistic immune effect?

One issue I have with this study is that I don’t think they successfully separated the effects of flagellar motility from host development initiation. This is because the non-rotating mutants would also have been less motile and therefore worse at infiltrating the host light organ. Their reduced CEA-inducing abilities may have been due to this, rather than lower LPS immune stimulation.

By covering flagellin, perhaps LPS provides more dispersible and customisable immune stimulation. Flagellin alone cannot do this, since it is highly conserved across all bacterial groups. I think further work should look into whether certain bacteria present flagellar sheaths during specific life cycle stages or environmental conditions. Some Vibrios drastically change their flagella when near a surface, so perhaps there are sheath changes which aid in host colonization?

Brennan, C. A., Hunt, J. R., Kremer, N., Krasity, B. C., Apicella, M. A., McFall-Ngai, M. J., & Ruby, E. G. (2014). A model symbiosis reveals a role for sheathed-flagellum rotation in the release of immunogenic lipopolysaccharide.eLife, 3.