Francisella tularensis
is the causative agent of tularemia. Because of its extreme infectivity and high mortality rate, this pathogen was classified as a biothreat agent.
Francisella
spp are strict aerobe and ubiquinone (UQ) has been previously identified in these bacteria. While the UQ biosynthetic pathways were extensively studied in
Escherichia coli
allowing the identification of fifteen Ubi-proteins to date, little is known about
Francisella
spp. In this study, and using
Francisella novicida
as a surrogate organism, we first identified UQ
8
as the major quinone found in the membranes of this bacterium. Then, we characterized the UQ biosynthetic pathway in
F. novicida
using a combination of bioinformatics, genetics and biochemical approaches. Our analysis disclosed the presence in
Francisella
of ten putative Ubi-proteins and we confirmed eight of them by heterologous complementation in
E. coli
. The UQ biosynthetic pathways from
F. novicida
and
E. coli
share a similar pattern. However, differences were highlighted: the decarboxylase remains unidentified in
Francisella
spp and homologs of the Ubi-proteins involved in the O
2
-independent UQ pathway are not present. This is in agreement with the strictly aerobic niche of this bacterium. Then,
via
two approaches, i.e. the use of an inhibitor (3-amino-4-hydroxybenzoic acid) and a transposon mutant, which both strongly impair the synthesis of UQ, we demonstrated that UQ is essential for the growth of
F. novicida
in a respiratory medium and contributes to its pathogenicity in
Galleria mellonella
used as an alternative animal model.
Importance
Francisella tularensis
is the causative bacterium of tularemia and is classified as a biothreat agent. Using multidisciplinary approaches, we investigated the ubiquinone (UQ) biosynthetic pathway that operates in
F. novicida
used as a surrogate. We showed that UQ
8
is the major quinone identified in the membranes of
Francisella novicida
. We identified a new competitive inhibitor, which strongly decreased the biosynthesis of UQ. Our demonstration of the crucial role of UQ for the respiratory metabolism of
F. novicida
and for the involving in its pathogenicity in the
Galleria mellonella
model should stimulate the search for selective inhibitors of bacterial UQ biosynthesis.