Genome Sequence Analysis of the Emerging Human Pathogenic Acetic Acid Bacterium Granulibacter bethesdensis

Chronic granulomatous disease (CGD) is an inherited immune deficiency characterized by increased susceptibility to infection withStaphylococcus , certain gram-negative bacteria, and fungi.Granulibacter bethesdensis , a newly described genus and species within the familyAcetobacteraceae , was recently isolated from four CGD patients residing in geographically distinct locales who presented with fever and lymphadenitis. We sequenced the genome of the reference strain ofGranulibacter bethesdensis , which was isolated from lymph nodes of the original patient. The genome contains 2,708,355 base pairs in a single circular chromosome, in which 2,437 putative open reading frames (ORFs) were identified, 1,470 of which share sequence similarity with ORFs in the nonpathogenic but relatedGluconobacter oxydans genome. Included in the 967 ORFs that are unique toG. bethesdensis are ORFs potentially important for virulence, adherence, DNA uptake, and methanol utilization. GC% values and best BLAST analysis suggested that some of these unique ORFs were recently acquired. Comparison ofG. bethesdensis to other known CGD pathogens demonstrated conservation of some putative virulence factors, suggesting possible common mechanisms involved in pathogenesis in CGD. Genotyping of the four patient isolates by use of a custom microarray demonstrated genome-wide variations in regions encoding DNA uptake systems and transcriptional regulators and in hypothetical ORFs.G. bethesdensis is a genetically diverse emerging human pathogen that may have recently acquired virulence factors new to this family of organisms.