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Differential Substrate Usage and Metabolic Fluxes in Francisella tularensis Subspecies holarctica and Francisella novicida
Ist Teil von
Frontiers in cellular and infection microbiology, 2017-06, Vol.7, p.275-275
Ort / Verlag
Switzerland: Frontiers Media S.A
Erscheinungsjahr
2017
Quelle
MEDLINE
Beschreibungen/Notizen
is an intracellular pathogen for many animals causing the infectious disease, tularemia. Whereas
subsp.
is highly pathogenic for humans,
is almost avirulent for humans, but virulent for mice. In order to compare metabolic fluxes between these strains, we performed
C-labeling experiments with
subsp.
wild type (beaver isolate),
subsp.
strain LVS, or
strain U112 in complex media containing either [U-
C
]glucose, [1,2-
C
]glucose, [U-
C
]serine, or [U-
C
]glycerol. GC/MS-based isotopolog profiling of amino acids, polysaccharide-derived glucose, free fructose, amino sugars derived from the cell wall, fatty acids, 3-hydroxybutyrate, lactate, succinate and malate revealed uptake and metabolic usage of all tracers under the experimental conditions with glucose being the major carbon source for all strains under study. The labeling patterns of the
subsp.
wild type were highly similar to those of the LVS strain, but showed remarkable differences to the labeling profiles of the metabolites from the
strain. Glucose was directly used for polysaccharide and cell wall biosynthesis with higher rates in
subsp.
or metabolized, with higher rates in
glycolysis and the non-oxidative pentose phosphate pathway (PPP). Catabolic turnover of glucose
gluconeogenesis was also observed. In all strains, Ala was mainly synthesized from pyruvate, although no pathway from pyruvate to Ala is annotated in the genomes of
and
. Glycerol efficiently served as a gluconeogenetic substrate in
, but only less in the
subsp.
strains. In any of the studied strains, serine did not serve as a major substrate and was not significantly used for gluconeogenesis under the experimental conditions. Rather, it was only utilized, at low rates, in downstream metabolic processes, e.g.,
acetyl-CoA in the citrate cycle and for fatty acid biosynthesis, especially in the
subsp.
strains. In summary, the data reflect differential metabolite fluxes in
subsp.
and
suggesting that the different utilization of substrates could be related to host specificity and virulence of
.