Serologic Reactivity to the Emerging Pathogen Granulibacter bethesdensis

Abstract

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.

Chronic Granulomatous Disease

“…It can have latent and active phases, similar to tuberculosis and has been identified from the United States, Panama, and Spain, suggesting wide distribution. Interestingly, while the rate of seropositivity for this organism is about 50% in CGD patients, the majority of whom have not had recognized infections, the rate of seropositivity is around 25% in normals, suggesting broad exposure and the possibility of a clinical syndrome yet to be identified (34). …”

Fulminant Sepsis Due to Granulibacter bethesdensis in a 4-Year-Old Boy With X-Linked Chronic Granulomatous Disease

“…Although it has been reported that 25% of healthy donors and 45% of patients with CGD have a serologic response to G. bethesdensis , 5 it is unclear if this bacterium can cause disease in healthy individuals or persist in a latent form. The primary mechanism of elimination of this organism is through reactive oxygen species production by polymorphonuclear neutrophils.…”

Methylotroph Infections and Chronic Granulomatous Disease

“…It also reduces nitrate and assimilates malate ( 10 ). Methanol dehydrogenase serology is currently under investigation as a potential supportive diagnostic or prognostic tool for tracking methylotroph infections, particularly those caused by G. bethesdensis ( 14 ).…”