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Granulibacter bethesdensis can infect patients with chronic granulomatous disease, an immunodeficiency caused by reduced phagocyte NADPH oxidase function. Intact G. bethesdensis ( Gb ) is hypostimulatory compared to Escherichia coli , i.e., cytokine production in human blood requires 10-100 times more G. bethesdensis CFU/mL than E. coli . To better understand the pathogenicity of G. bethesdensis , we isolated its lipopolysaccharide ( Gb LPS) and characterized its lipid A. Unlike with typical Enterobacteriaceae , the release of presumptive Gb lipid A from its LPS required a strong acid. NMR and mass spectrometry demonstrated that the carbohydrate portion of the isolated glycolipid consists of α-Man p -(1→4)-β-Glc p N3N-(1→6)-α-Glc p N-(1⇿1)-α-Glc p A tetra-saccharide substituted with five acyl chains: the amide-linked N-3' 14:0(3-OH), N-2' 16:0(3-O16:0), and N-2 18:0(3-OH) and the ester-linked O-3 14:0(3-OH) and 16:0. The identification of glycero-d-talo-oct-2-ulosonic acid (Ko) as the first constituent of the core region of the LPS that is covalently attached to GlcpN3N of the lipid backbone may account for the acid resistance of Gb LPS. In addition, the presence of Ko and only five acyl chains may explain the >10-fold lower proinflammatory potency of Gb Ko-lipidA compared to E. coli lipid A, as measured by cytokine induction in human blood. These unusual structural properties of the G.bethesdensis Ko-lipid A glycolipid likely contribute to immune evasion during pathogenesis and resistance to antimicrobial peptides.

Purpose: Adenitis for which no causative organism can be isolated is a common occurrence in patients with chronic granulomatous disease (CGD). Here we identify Acidomonas methanolica as a pathogen associated with adenitis in a patient with CGD., Methods: The causative pathogen was obtained after prolonged incubation of an excised lymph node in thioglycolate broth. Identification was carried out by sequencing the 16s rRNA. Immunoblots were prepared utilizing protein extracts from the case patient's A. methanolica isolate, an ATCC type strain of A. methanolica and G. bethesdensis., Results: Fastidious gram-negative rods grew after prolonged incubation of an excised lymph node in thioglycolate broth. Sequencing of the 16s rRNA identified the organism as A. methanolica. Immunoblot confirmed the pathogen's role in the patient's adenitis by showing the patient's specific immune response to the organism., Conclusions: A. methanolica is the second member of the family, Acetobacteaceae to be associated with adenitis in patients with CGD.

Chronic granulomatous disease (CGD) is characterized by frequent infections, most of which are curable. Granulibacter bethesdensis is an emerging pathogen in patients with CGD that causes fever and necrotizing lymphadenitis. However, unlike typical CGD organisms, this organism can cause relapse after clinical quiescence. To better define whether infections were newly acquired or recrudesced, we use comparative bacterial genomic hybridization to characterize 11 isolates obtained from 5 patients with CGD from North and Central America. Genomic typing showed that 3 patients had recurrent infection months to years after apparent clinical cure. Two patients were infected with the same strain as previously isolated, and 1 was infected with a genetically distinct strain. This organism is multidrug resistant, and therapy required surgery and combination antimicrobial drugs, including long-term ceftriaxone. G. bethesdensis causes necrotizing lymphadenitis in CGD, which may recur or relapse.

Chronic granulomatous disease was diagnosed in a 10-year-old boy who, after some weeks' decline, developed acute respiratory distress leading to multiple organ failure and death. All microbiological analyses were negative, except two blood cultures from which the novel bacterium Granulibacter bethesdensis was isolated.

A Gram-negative, aerobic, coccobacillus to rod-shaped bacterium was isolated from three patients with chronic granulomatous disease. The organism was subjected to a polyphasic taxonomic study. A multilocus phylogenetic analysis based on the 16S rRNA gene, the internal transcribed spacer (ITS) region and the RecA protein demonstrated that the organism belongs to a new sublineage within the acetic acid bacteria in the family Acetobacteraceae. Phenotypic features are summarized as follows: the organism grew at an optimum temperature of 35-37 degrees C and optimum pH of 5.0-6.5. It produced a yellow pigment, oxidized lactate and acetate, the latter weakly, produced little acetic acid from ethanol and could use methanol as a sole carbon source. The two major fatty acids were a straight-chain unsaturated acid (C18:1omega7c) and C16:0. The DNA base composition was 59.1 mol% G+C. The very weak production of acetic acid from ethanol, the ability to use methanol, the yellow pigmentation and high optimum temperature for growth distinguished this organism from other acetic acid bacteria. The unique phylogenetic and phenotypic characteristics suggest that the bacterium should be classified within a separate genus, for which the name Granulibacter bethesdensis gen. nov., sp. nov. is proposed. The type strain is CGDNIH1T (=ATCC BAA-1260T=DSM 17861T).