Gene/Protein
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Compound
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Gene/Protein
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Target Concepts:
Gene/Protein
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Query: UNIPROT:P43026 (
lipopolysaccharide
)
62,215
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Coxiella burnetii
, the etiologic agent of acute Q fever and
chronic endocarditis
, has a unique biphasic life cycle, which includes a metabolically active intracellular form that occupies a large lysosome-derived acidic vacuole.
C. burnetii
is the only bacterium known to thrive within such an hostile intracellular niche, and this ability is fundamental to its pathogenicity; however, very little is known about genes that facilitate
Coxiella
's intracellular growth. Recent studies indicate that
C. burnetii
evolved from a tick-associated ancestor and that the metabolic capabilities of
C. burnetii
are different from that of
Coxiella
-like bacteria found in ticks. Horizontally acquired genes that allow
C. burnetii
to infect and grow within mammalian cells likely facilitated the host shift; however, because of its obligate intracellular replication,
C. burnetii
would have lost most genes that have been rendered redundant due to the availability of metabolites within the host cell. Based on these observations, we reasoned that horizontally derived biosynthetic genes that have been retained in the reduced genome of
C. burnetii
are ideal candidates to begin to uncover its intracellular metabolic requirements. Our analyses identified a large number of putative foreign-origin genes in
C. burnetii
, including tRNA
Glu
2 that is potentially required for heme biosynthesis, and genes involved in the production of
lipopolysaccharide
-a virulence factor, and of critical metabolites such as fatty acids and biotin. In comparison to wild-type
C. burnetii
, a strain that lacks tRNA
Glu
2 exhibited reduced growth, indicating its importance to
Coxiella
's physiology. Additionally, by using chemical agents that block heme and biotin biosyntheses, we show that these pathways are promising targets for the development of new anti-
Coxiella
therapies.
...
PMID:Horizontally Acquired Biosynthesis Genes Boost
Coxiella burnetii
's Physiology. 2854 Feb 58
