Methylotroph Infections and Chronic Granulomatous Disease

E. Liana Falcone; Jennifer R. Petts; Mary Beth Fasano; Bradley Ford; William M. Nauseef; João Farela Neves; Maria João Simões; Millard L. Tierce IV; M. Teresa de la Morena; David E. Greenberg; Christa S. Zerbe; Adrian M. Zelazny; Steven M. Holland


Emerging Infectious Diseases. 2016;22(3):404-409. 

In This Article

Abstract and Introduction


Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in production of phagocyte-derived reactive oxygen species, which leads to recurrent infections with a characteristic group of pathogens not previously known to include methylotrophs. Methylotrophs are versatile environmental bacteria that can use single-carbon organic compounds as their sole source of energy; they rarely cause disease in immunocompetent persons. We have identified 12 infections with methylotrophs (5 reported here, 7 previously reported) in patients with CGD. Methylotrophs identified were Granulibacter bethesdensis (9 cases), Acidomonas methanolica (2 cases), and Methylobacterium lusitanum (1 case). Two patients in Europe died; the other 10, from North and Central America, recovered after prolonged courses of antimicrobial drug therapy and, for some, surgery. Methylotrophs are emerging as disease-causing organisms in patients with CGD. For all patients, sequencing of the 16S rRNA gene was required for correct diagnosis. Geographic origin of the methylotroph strain may affect clinical management and prognosis.


Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent infections of the lung, skin, lymph nodes, and liver, as well as granulomatous inflammation affecting those organs and hollow viscera. The immunodeficiency results from deficiencies in any 1 of the 5 subunits forming the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 2 (Nox2)–based complex, which leads to impaired production of reactive oxygen species in phagocytes. Defects in the Nox2 (gp91 phox ) enzymatic subunit (CYBB [cytochrome b-245, β polypeptide]) are inherited in an X-linked manner, whereas defects in subunits p47 phox (NCF1 [neutrophil cytosolic factor 1]), p22 phox (CYBA [cytochrome b-245, α polypeptide]), p67 phox (NCF2 [neutrophil cytosolic factor 2]), and p40 phox (NCF4 [neutrophil cytosolic factor 4]) are inherited in an autosomal recessive manner.[1,2]

CGD infections are often caused by a characteristic group of pathogens, including Staphylococcus aureus, Serratia marcescens, Burkholdheria cepacia complex, Nocardia spp., and Aspergillus spp..[1] However, new pathogens are emerging, and some reportedly are found almost exclusively in patients with CGD. Methylotrophs are bacteria that can use single-carbon organic compounds as their sole source of energy, the widespread availability of which makes these organisms versatile environmental inhabitants. However, they rarely cause disease in immunocompetent persons.[3]

We previously reported 7 methylotroph infections in patients with CGD and here describe 5 more (Table). From these 12 infections, we have isolated the methylotrophs Granulibacter bethesdensis, Acidomonas methanolica, and Methylobacterium lusitanum. These infections were difficult to diagnose and required prolonged courses of antimicrobial drugs and sometimes surgery for complete resolution.