Granulibacter spp. isolates obtained from different chronic granulomatous disease patients are heterogeneous in responses to innate immune defenses

Wednesday, September 24, 2014 — Poster Session IV
10:00 a.m. –12:00 p.m.	FAES Academic Center	NIAID	MICROBIO-1

Authors

• J. Chu
• A.M. Pettinato
• S.M. Holland
• K.A. Zarember
• J.I. Gallin

Abstract

Granulibacter bethesdensis, a member of the Acetobacteraceae family, causes recurrent infections in patients with Chronic Granulomatous Disease (CGD), a deficiency in the NADPH oxidase. Nine isolates of this organism have been obtained from seven NIH CGD patients and two lethal cases in Spain and Portugal. We previously demonstrated that isolate NIH1.1 was killed by normal, but not CGD, polymorphonuclear leukocytes (PMN) and monocytes and persisted in CGD monocyte-derived macrophages. To further characterize Granulibacter and dissect potential differences between the available isolates (NIH1-7, Portuguese), we examined bacterial growth rates, ultrastructure, sensitivities to normal PMN and monocyte killing, and activation of serum complement and the normal PMN respiratory burst. Growth of the lethal Portuguese isolate was faster than NIH isolates and differences in capsule thickness and carbohydrate content were observed amongst the isolates. Interestingly, the Portuguese isolate did not bind complement proteins C3 and C9 and failed to stimulate a respiratory burst, yet could be killed by normal PMN. Isolate NIH4.1 was resistant to normal PMN killing and isolate NIH4.1 and the Portuguese isolate were resistant to normal monocyte killing. These studies indicate that the lethal Portuguese isolate differed from NIH isolates by less stimulation of innate immune responses.

back to top