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Abstract

Bacterial flagellar motility plays an important role in many processes
that occur at surfaces or in hydrogels, including adhesion, biofilm
formation, and bacterium-host interactions. Consequently, expression of
flagellar genes, as well as genes involved in biofilm formation and
virulence, can be regulated by the surface contact. In a few bacterial
species, flagella themselves are known to serve as mechanosensors, where
an increased load on flagella experienced during surface contact or
swimming in viscous media controls gene expression. In this study, we
show that gene regulation by motility-dependent mechanosensing is common
among pathogenic Escherichia coli strains. This regulatory mechanism
requires flagellar rotation, and it enables pathogenic E. coli to
repress flagellar genes at low loads in liquid culture, while activating
motility in porous medium (soft agar) or upon surface contact. It also
controls several other cellular functions, including metabolism and
signaling. The mechanosensing response in pathogenic E. coli depends on
the negative regulator of motility, RflP (YdiV), which inhibits basal
expression of flagellar genes in liquid. While no conditional inhibition
of flagellar gene expression in liquid and therefore no upregulation in
porous medium was observed in the wild-type commensal or laboratory
strains of E. coli, mechanosensitive regulation could be recovered by
overexpression of RflP in the laboratory strain. We hypothesize that
this conditional activation of flagellar genes in pathogenic E. coli
reflects adaptation to the dual role played by flagella and motility
during infection.
IMPORTANCE Flagella and motility are widespread virulence factors among
pathogenic bacteria. Motility enhances the initial host colonization,
but the flagellum is a major antigen targeted by the host immune system.
Here, we demonstrate that pathogenic E. coli strains employ a
mechanosensory function of the flagellar motor to activate flagellar
expression under high loads, while repressing it in liquid culture. We
hypothesize that this mechanism allows pathogenic E. coli to regulate
its motility dependent on the stage of infection, activating flagellar
expression upon initial contact with the host epithelium, when motility
is beneficial, but reducing it within the host to delay the immune
response.