ABSTRACT
The enterohepatic
Helicobacter
species
Helicobacter hepaticus
colonizes the murine intestinal and hepatobiliary tract and is associated with chronic intestinal inflammation, gall stone formation, hepatitis, and hepatocellular carcinoma. Thus far, the role of
H. hepaticus
motility and flagella in intestinal colonization is unknown. In other, closely related bacteria, late flagellar genes are mainly regulated by the sigma factor FliA (σ
28
). We investigated the function of the
H. hepaticus
FliA in gene regulation, flagellar biosynthesis, motility, and murine colonization. Competitive microarray analysis of the wild type versus an isogenic
fliA
mutant revealed that 11 genes were significantly more highly expressed in wild-type bacteria and 2 genes were significantly more highly expressed in the
fliA
mutant. Most of these were flagellar genes, but four novel FliA-regulated genes of unknown function were identified.
H. hepaticus
possesses two identical copies of the gene encoding the FliA-dependent major flagellin subunit FlaA (open reading frames HH1364 and HH1653). We characterized the phenotypes of mutants in which
fliA
or one or both copies of the
flaA
gene were knocked out.
flaA
_
1 flaA
_
2
double mutants and
fliA
mutants did not synthesize detectable amounts of FlaA and possessed severely truncated flagella. Also, both mutants were nonmotile and unable to colonize mice. Mutants with either
flaA
gene knocked out produced flagella morphologically similar to those of wild-type bacteria and expressed FlaA and FlaB.
flaA
_
1
mutants which had flagella but displayed reduced motility did not colonize mice, indicating that motility is required for intestinal colonization by
H. hepaticus
and that the presence of flagella alone is not sufficient.
