Innate Immunity against Granulibacter bethesdensis, an Emerging Gram-Negative Bacterial Pathogen

Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Infection and immunity (Impact Factor: 3.73). 12/2011; 80(3):975-81. DOI: 10.1128/IAI.05557-11
Source: PubMed


Acetic acid bacteria were previously considered nonpathogenic in humans. However, over the past decade, five genera of Acetobacteraceae have been isolated from patients with inborn or iatrogenic immunodeficiencies. Here, we describe the first studies of the
interactions of the human innate immune system with a member of this bacterial family, Granulibacter bethesdensis, an emerging pathogen in patients with chronic granulomatous disease (CGD). Efficient phagocytosis of G. bethesdensis by normal and CGD polymorphonuclear leukocytes (CGD PMN) required heat-labile serum components (e.g., C3), and binding of
C3 and C9 to G. bethesdensis was detected by immunoblotting. However, this organism survived in human serum concentrations of ≥90%, indicating a high
degree of serum resistance. Consistent with the clinical host tropism of G. bethesdensis, CGD PMN were unable to kill this organism, while normal PMN, in the presence of serum, reduced the number of CFU by about
50% after a 24-h coculture. This finding, together with the observations that G. bethesdensis was sensitive to H2O2 but resistant to LL-37, a human cationic antimicrobial peptide, suggests an inherent resistance to O2-independent killing. Interestingly, 10 to 100 times greater numbers of G. bethesdensis were required to achieve the same level of reactive oxygen species (ROS) production induced by Escherichia coli in normal PMN. In addition to the relative inability of the organism to elicit production of PMN ROS, G. bethesdensis inhibited both constitutive and FAS-induced PMN apoptosis. These properties of reduced PMN activation and resistance to nonoxidative
killing mechanisms likely play an important role in G. bethesdensis pathogenesis.

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Available from: Meggan Czapiga, Jul 10, 2014
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