A novel bacterium associated with lymphadenitis in a patient with chronic granulomatous disease.

David E. Greenberg, Li Ding, Adrian M. Zelazny, Frida Stock, Alexandra Wong, Victoria L. Anderson, Georgina Miller, David E. Kleiner, Allan R. Tenorio, Lauren Brinster, David W. Dorward, Patrick R. Murray, Steven M. Holland

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system causing defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections. We identified a novel gram-negative rod in excised lymph nodes from a patient with CGD. Gram-negative rods grew on charcoal-yeast extract, but conventional tests could not identify it. The best 50 matches of the 16S rRNA (using BLAST) were all members of the family Acetobacteraceae, with the closest match being Gluconobacter sacchari. Patient serum showed specific band recognition in whole lysate immunoblot. We used mouse models of CGD to determine whether this organism was a genuine CGD pathogen. Intraperitoneal injection of gp91(phox -/-) (X-linked) and p47 (phox -/-) (autosomal recessive) mice with this bacterium led to larger burdens of organism recovered from knockout compared with wild-type mice. Knockout mouse lymph nodes had histopathology that was similar to that seen in our patient. We recovered organisms with 16S rRNA sequence identical to the patient's original isolate from the infected mice. We identified a novel gram-negative rod from a patient with CGD. To confirm its pathogenicity, we demonstrated specific immune reaction by high titer antibody, showed that it was able to cause similar disease when introduced into CGD, but not wild-type mice, and we recovered the same organism from pathologic lesions in these mice. Therefore, we have fulfilled Koch's postulates for a new pathogen. This is the first reported case of invasive human disease caused by any of the Acetobacteraceae. Polyphasic taxonomic analysis shows this organism to be a new genus and species for which we propose the name Granulobacter bethesdensis.

Original languageEnglish (US)
JournalPLoS Pathogens
Volume2
Issue number4
DOIs
StatePublished - Apr 2006

Fingerprint

Chronic Granulomatous Disease
Lymphadenitis
Bacteria
Acetobacteraceae
Gluconobacter
Lymph Nodes
NADPH Oxidase
Poisons
Charcoal
Phagocytes
Rare Diseases
Intraperitoneal Injections
Knockout Mice
Names
Virulence
Yeasts
Oxygen
Antibodies
Infection
Serum

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

A novel bacterium associated with lymphadenitis in a patient with chronic granulomatous disease. / Greenberg, David E.; Ding, Li; Zelazny, Adrian M.; Stock, Frida; Wong, Alexandra; Anderson, Victoria L.; Miller, Georgina; Kleiner, David E.; Tenorio, Allan R.; Brinster, Lauren; Dorward, David W.; Murray, Patrick R.; Holland, Steven M.

In: PLoS Pathogens, Vol. 2, No. 4, 04.2006.

Research output: Contribution to journalArticle

Greenberg, DE, Ding, L, Zelazny, AM, Stock, F, Wong, A, Anderson, VL, Miller, G, Kleiner, DE, Tenorio, AR, Brinster, L, Dorward, DW, Murray, PR & Holland, SM 2006, 'A novel bacterium associated with lymphadenitis in a patient with chronic granulomatous disease.', PLoS Pathogens, vol. 2, no. 4. https://doi.org/10.1371/journal.ppat.0020028
Greenberg, David E. ; Ding, Li ; Zelazny, Adrian M. ; Stock, Frida ; Wong, Alexandra ; Anderson, Victoria L. ; Miller, Georgina ; Kleiner, David E. ; Tenorio, Allan R. ; Brinster, Lauren ; Dorward, David W. ; Murray, Patrick R. ; Holland, Steven M. / A novel bacterium associated with lymphadenitis in a patient with chronic granulomatous disease. In: PLoS Pathogens. 2006 ; Vol. 2, No. 4.
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AU - Anderson, Victoria L.

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AU - Kleiner, David E.

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