Serologic reactivity to the emerging pathogen Granulibacter bethesdensis.
BACKGROUND
Granulibacter bethesdensis is a recently described member of the Acetobacteraceae family that has been isolated from patients with chronic granulomatous disease (CGD). Its pathogenesis, environmental reservoir(s), and incidence of infection among CGD patients and the general population are unknown.


METHODS
Detected antigens were identified by mass spectroscopy after 2-dimensional electrophoresis and immunoaffinity chromatography. The prevalence of Granulibacter immunoreactivity was assessed through immunoblotting and enzyme-linked immunosorbent assay (ELISA).


RESULTS
Methanol dehydrogenase (MDH) and formaldehyde-activating enzyme were recognized during analysis of sera from infected patients. Unique patterns of immunoreactive bands were identified in Granulibacter extracts, compared with extracts of other Acetobacteraceae species. By use of criteria based on these specific bands, specimens from 79 of 175 CGD patients (45.1%) and 23 of 93 healthy donors (24.7%) reacted to all 11 bands. An ELISA that used native MDH to capture and detect immunoglobulin G was developed and revealed high-titer MDH seroreactivity in culture-confirmed cases and 5 additional CGD patients. Testing of samples collected prior to culture-confirmed infection demonstrated instances of recent seroconversion, as well as sustained seropositivity. Infection of CGD mice with G. bethesdensis confirmed acquisition of high-titer antibody-recognizing MDH.


CONCLUSIONS
These serologic tests suggest that Granulibacter immunoreactivity is more common among CGD patients and, perhaps, among healthy donors than was previously suspected. This finding raises the possibility that clinical presentations of Granulibacter infection may be underappreciated.
Laboratory of Clinical Infectious Diseases, Bethesda, MD, USA. david.greenberg@utsouthwestern.edu
David E
DE
Greenberg
Adam R
AR
Shoffner
Kimberly R
KR
Marshall-Batty
Kriti
K
Arora
Ming
M
Zhao
Raynaldo
R
Martin
Li
L
Ding
Carl H
CH
Hammer
Pamela A
PA
Shaw
Douglas B
DB
Kuhns
Harry L
HL
Malech
John I
JI
Gallin
Kol A
KA
Zarember
Steven M
SM
Holland
D016947:Acetobacteraceae / Q000201:enzymology / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D021821:Communicable Diseases, Emerging / Q000276:immunology / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D016905:Gram-Negative Bacterial Infections / Q000276:immunology / Q000382:microbiology*; D006105:Granulomatous Disease, Chronic / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D016036:Seroepidemiologic Studies; D012698:Serologic Tests; D055815:Young Adult
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D000429:Alcohol Oxidoreductases; C019641:alcohol dehydrogenase (acceptor)