Wolbachia Interferes with Ferritin Expression and Iron Metabolism in Insects

Abstract

Wolbachia is an intracellular bacterium generally described as being a facultative reproductive parasite. However, Wolbachia is necessary for oogenesis completion in the wasp Asobara tabida. This dependence has evolved recently as a result of interference with apoptosis during oogenesis. Through comparative transcriptomics between symbiotic and aposymbiotic individuals, we observed a differential expression of ferritin, which forms a complex involved in iron storage. Iron is an essential element that is in limited supply in the cell. However, it is also a highly toxic precursor of Reactive Oxygen Species (ROS). Ferritin has also been shown to play a key role in host–pathogen interactions. Measuring ferritin by quantitative RT-PCR, we confirmed that ferritin was upregulated in aposymbiotic compared to symbiotic individuals. Manipulating the iron content in the diet, we showed that iron overload markedly affected wasp development and induced apoptotic processes during oogenesis in A. tabida, suggesting that the regulation of iron homeostasis may also be related to the obligate dependence of the wasp. Finally, we demonstrated that iron metabolism is influenced by the presence of Wolbachia not only in the obligate mutualism with A. tabida, but also in facultative parasitism involving Drosophila simulans and in Aedes aegypti cells. In these latter cases, the expression of Wolbachia bacterioferritin was also increased in the presence of iron, showing that Wolbachia responds to the concentration of iron. Our results indicate that Wolbachia may generally interfere with iron metabolism. The high affinity of Wolbachia for iron might be due to physiological requirement of the bacterium, but it could also be what allows the symbiont to persist in the organism by reducing the labile iron concentration, thus protecting the cell from oxidative stress and apoptosis. These findings also reinforce the idea that pathogenic, parasitic and mutualistic intracellular bacteria all use the same molecular mechanisms to survive and replicate within host cells. By impacting the general physiology of the host, the presence of a symbiont may select for host compensatory mechanisms, which extends the possible consequences of persistent endosymbiont on the evolution of their hosts.

Analysis of gene expression from theWolbachiagenome of a filarial nematode supports both metabolic and defensive roles within the symbiosis

“…In D. melanogaster, wMel was shown to confer a fecundity benefit on flies reared on both ecologically relevant, iron-restricted diets and on artificial, iron-overloaded diets (Brownlie et al 2009). Moreover, in D. simulans reared under high-iron conditions, flies infected with wRi absorbed more iron than did uninfected flies, yet the up-regulation of host ferritin was lower than that observed in uninfected flies (Kremer et al 2009). In this system, increased expression of Bfr by wRi apparently compensated for the host response, although this mechanism cannot apply to wOo, which has lost the Bfr gene.…”

Selfish genetic elements, genetic conflict, and evolutionary innovation

“…Different strains of Wolbachia can be reciprocally incompatible because of differences in their modification-rescue system or host genetic interactions. An interesting possible case of evolved dependency occurs in the wasp Asobara tabida (71). Removal of Wolbachia results in sterility as a result of elevated apoptosis in the developing female reproductive tract.…”

Symbiosis as a General Principle in Eukaryotic Evolution

“…This important effect was first shown by research on the relationship between a parasitic wasp, Asobara tabida, and the vertically transmitted bacterium Wolbachia. Several lines of evidence suggest that Wolbachia induces oxidative stress and a linked dampening of apoptotic signaling, probably as a result of disruption of iron metabolism (Kremer et al 2009). As a likely consequence, elimination of Wolbachia by antibiotic treatment results in massive apoptosis ( programmed cell death) of the ovaries, leaving the wasp reproductively sterile.…”