Glucose and Glycogen Metabolism in Brugia malayi Is Associated with Wolbachia Symbiont Fitness

Abstract

Wolbachia are endosymbiotic bacteria found in the majority of arthropods and filarial nematodes of medical and veterinary importance. They have evolved a wide range of symbiotic associations. In filarial nematodes that cause human lymphatic filariasis (Wuchereria bancrofti, Brugia malayi) or onchocerciasis (Onchocerca volvulus), Wolbachia are important for parasite development, reproduction and survival. The symbiotic bacteria rely in part on nutrients and energy sources provided by the host. Genomic analyses suggest that the strain of Wolbachia found in B. malayi (wBm) lacks the genes for two glycolytic enzymes—6-phosphofructokinase and pyruvate kinase—and is thus potentially unable to convert glucose into pyruvate, an important substrate for energy generation. The Wolbachia surface protein, wBm00432, is complexed to six B. malayi glycolytic enzymes, including aldolase. In this study we characterized two B. malayi aldolase isozymes and found that their expression is dependent on Wolbachia fitness and number. We confirmed by immuno-transmission electron microscopy that aldolase is associated with the Wolbachia surface. RNAi experiments suggested that aldolase-2 plays a significant role in both Wolbachia survival and embryogenesis in B. malayi. Treatment with doxycycline reduced Wolbachia fitness and increased the amount of both glucose and glycogen detected in the filarial parasite, indicating that glucose metabolism and glycogen storage in B. malayi are associated with Wolbachia fitness. This metabolic co-dependency between Wolbachia and its filarial nematode indicates that glycolysis could be a shared metabolic pathway between the bacteria and B. malayi, and thus a potential new target for anti-filarial therapy.

Wolbachia Endosymbionts Modify Drosophila Ovary Protein Levels in a Context-Dependent Manner

“…From a nutritional standpoint, an elevated abundance of proteases and proteasome subunits is consistent with the possibility of increased amino acid availability for Wolbachia ( 79 ). The upregulation of glycogen phosphorylase complements recent work using Brugia malayi nematodes, which indicated that Wolbachia bacteria induce the upregulation of glycolytic enzymes ( 80 ). An increased local availability of pyruvate is hypothesized to benefit Wolbachia ( 81 ).…”

Growth kinetics of endosymbiont Wolbachia in the common bed bug, Cimex lectularius

“…Additionally, the ratio of protein to carbohydrate intake modulated Wolbachia abundance in Drosophila 43 . Glucose metabolism and glycogen storage in B. malayi are linked with Wolbachia fitness in a metabolic co-dependency pathway shared between the bacteria and its nematode host 44 . In the B. malayi system, w Bm lacked genes for 2 glycolytic enzymes, 6-phosphofructokinase and pyruvate kinase, and were unable to convert glucose into pyruvate 44 .…”

Wolbachia and Sirtuin-4 interaction is associated with alterations in host glucose metabolism and bacterial titer

“…In the mutually exclusive association between Wolbachia and filarial nematodes, evidence indicates that Wolbachia plays a role in heme provisioning [ 27 , 28 ], while directly relying on host pyruvate production, through glycolysis, for its own survival. Removal of Wolbachia via antibiotic treatment led to increased host levels of glucose and glycogen [ 29 , 30 ].…”