In silico biosynthesis of virenose, a methylated deoxy-sugar unique to Coxiella burnetii lipopolysaccharide
1 Department of Rickettsiology, Institute of Virology, Slovak Academy of Sciences, Dubravska cesta, 9, Bratislava, 845 05, Slovakia
2 Laboratory of Protein Evolution, Institute of Molecular Biology, Slovak Academy of Sciences, Bratislava, 845 51, Slovakia
3 USDA, Agricultural Research Service, Plant Genetics Research Unit, Columbia, MO, 65211, USA
4 Interdisciplinary Plant Group, University of Missouri, Columbia, MO, 65211, USA
5 Department of Biochemistry, University of Missouri, Columbia, MO, 65211, USA
6 Centre for Molecular Medicine, Slovak Academy of Sciences, Bratislava, 831 01, Slovakia
Proteome Science 2012, 10:67 doi:10.1186/1477-5956-10-67Published: 15 November 2012
Coxiella burnetii is Gram-negative bacterium responsible for the zoonosis Q-fever. While it has an obligate intracellular growth habit, it is able to persist for extended periods outside of a host cell and can resist environmental conditions that would be lethal to most prokaryotes. It is these extracellular bacteria that are the infectious stage encountered by eukaryotic hosts. The intracellular form has evolved to grow and replicate within acidified parasitophorous vacuoles. The outer coat of C. burnetii comprises a complex lipopolysaccharide (LPS) component that includes the unique methylated-6-deoxyhexose, virenose. Although potentially important as a biomarker for C. burnetii, the pathway for its biosynthesis remains obscure.
The 6-deoxyhexoses constitute a large family integral to the LPS of many eubacteria. It is believed that precursors of the methylated-deoxyhexoses traverse common early biosynthetic steps as nucleotide-monosaccharides. As a prelude to a full biosynthetic characterization, we present herein the results from bioinformatics-based, proteomics-supported predictions of the pathway for virenose synthesis. Alternative possibilities are considered which include both GDP-mannose and TDP-glucose as precursors.
We propose that biosynthesis of the unique C. burnetii biomarker, virenose, involves an early pathway similar to that of other C-3’-methylated deoxysugars which then diverges depending upon the nucleotide-carrier involved. The alternatives yield either the D- or L-enantiomers of virenose. Both pathways require five enzymatic steps, beginning with either glucose-6-phosphate or mannose-6-phosphate. Our in silico results comprise a model for virenose biosynthesis that can be directly tested. Definition of this pathway should facilitate the development of therapeutic agents useful for treatment of Q fever, as well as allowing improvements in the methods for diagnosing this highly infectious disease.