Abstract
The genomes of
Helicobacter
species colonizing the mammalian gastric mucosa (like
Helicobacter pylori
) contain a large number of genes annotated as iron acquisition genes but only few nickel acquisition genes, which contrasts with the central position of nickel in the urease-mediated acid resistance of these gastric pathogens. In this study we have investigated the predicted iron and nickel acquisition systems of the ferret pathogen
Helicobacter mustelae
. The expression of the outer membrane protein-encoding
frpB2
gene was iron and Fur repressed, whereas the expression of the ABC transporter genes
fecD
and
ceuE
was iron and Fur independent. The inactivation of the two
tonB
genes showed that TonB1 is required for heme utilization, whereas the absence of TonB2 only marginally affected iron-dependent growth but led to reduced cellular nickel content and urease activity. The inactivation of the
fecD
and
ceuE
ABC transporter genes did not affect iron levels but resulted in significantly reduced urease activity and cellular nickel content. Surprisingly, the inactivation of the
nixA
nickel transporter gene affected cellular nickel content and urease activity only when combined with the inactivation of other nickel acquisition genes, like
fecD
or
ceuE
. The FecDE ABC transporter is not specific for nickel, since an
fecD
mutant also showed reduced cellular cobalt levels and increased cobalt resistance. We conclude that the
H. mustelae fecDE
and
ceuE
genes encode an ABC transporter involved in nickel and cobalt acquisition, which works independently of the nickel transporter NixA, while TonB2 is required primarily for nickel acquisition, with TonB1 being required for heme utilization.