Abstract
Cat scratch fever (also known as cat scratch disease and bartonellosis) is an infectious disease caused by the proteobacterium Bartonella henselae following a cat scratch. Although the infection usually resolves spontaneously without treatment in healthy adults, bartonellosis may lead to severe complications in young children and immunocompromised patients, and there is new evidence suggesting that B. henselae may be associated with a broader range of clinical symptoms then previously believed. The genome of B. henselae contains genes for two putative Nudix hydrolases, BH02020 and BH01640 (KEGG). Nudix proteins play an important role in regulating the intracellular concentration of nucleotide cofactors and signaling molecules. The amino-acid sequence of BH02020 is similar to that of the prototypical member of the Nudix superfamily, Escherichia coli MutT, a protein that is best known for its ability to neutralize the promutagenic compound 7,8-dihydro-8-oxoguanosine triphosphate. Here, the crystal structure of BH02020 (Bh-MutT) in the Mg(2+)-bound state was determined at 2.1 Å resolution (PDB entry 3hhj). As observed in all Nudix hydrolase structures, the α-helix of the highly conserved `Nudix box' in Bh-MutT is one of two helices that sandwich a four-stranded mixed β-sheet with the central two β-strands parallel to each other. The catalytically essential divalent cation observed in the Bh-MutT structure, Mg(2+), is coordinated to the side chains of Glu57 and Glu61. The structure is not especially robust; a temperature melt obtained using circular dichroism spectroscopy shows that Bh-MutT irreversibly unfolds and precipitates out of solution upon heating, with a T(m) of 333 K.
Highlights
Cat scratch fever is a bacterial infection characterized by a bump or blister at the original site of entry, swollen lymph nodes, headaches and overall general discomfort
As techniques to diagnosis the presence of B. henselae have improved, there is a new concern that it may be responsible for a broader range of clinical symptoms, including prolonged fever of unknown origin (Florin et al, 2008)
The crystal structure of Bh-MutT is similar to the structures reported for other Nudix hydrolases
Summary
Cat scratch fever ( known as cat scratch disease and bartonellosis) is a bacterial infection characterized by a bump or blister at the original site of entry, swollen lymph nodes, headaches and overall general discomfort. The etiological agents responsible for the disease are bacteria from the fastidious hemotropic Gram-negative genus Bartonella (Chomel & Kasten, 2010). This genus contains 19 species, of which six have been associated with the human disease (Florin et al, 2008). As the name of the disease suggests, the chief reservoir for B. henselae is the domestic cat, with the bacteria being transmitted to humans primarily via scratches (Florin et al, 2008) It is debatable whether cats themselves become ill owing to B. henselae infection (Chomel et al, 1996). Owing to the widening spectrum of B. henselae infections and the widespread presence of B. henselae
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