Iron Necessity: The Secret of Wolbachia's Success?

Abstract

The bacterium Wolbachia (order Rickettsiales) is probably the world's most successful vertically-transmitted symbiont, distributed among a staggering 40% of terrestrial arthropod species. Wolbachia has great potential in vector control due to its ability to manipulate its hosts' reproduction and to impede the replication and dissemination of arboviruses and other pathogens within haematophagous arthropods. In addition, the unexpected presence of Wolbachia in filarial nematodes of medical and veterinary importance has provided an opportunity to target the adult worms of Wuchereria bancrofti, Onchocerca volvulus, and Dirofilaria immitis with safe drugs such as doxycycline. A striking feature of Wolbachia is its phenotypic plasticity between (and sometimes within) hosts, which may be underpinned by its ability to integrate itself into several key processes within eukaryotic cells: oxidative stress, autophagy, and apoptosis. Importantly, despite significant differences in the genomes of arthropod and filarial Wolbachia strains, these nexuses appear to lie on a continuum in different hosts. Here, we consider how iron metabolism may represent a fundamental aspect of host homeostasis that is impacted by Wolbachia infection, connecting disparate pathways ranging from the provision of haem and ATP to programmed cell death, aging, and the recycling of intracellular resources. Depending on how Wolbachia and host cells interact across networks that depend on iron, the gradient between parasitism and mutualism may shift dynamically in some systems, or alternatively, stabilise on one or the other end of the spectrum.

The transcriptome of the mosquito Aedes fluviatilis (Diptera: Culicidae), and transcriptional changes associated with its native Wolbachia infection

“…Of the 42 identified Wolbachia contigs, 22 were hypothetical proteins with unknown function. Interestingly, one contig was a heme biosynthesis protein, which suggests that w Flu promotes heme production, and provides further evidence to support the theory that Wolbachia alters host iron and redox homeostasis, even amongst native associations [36, 37]. We also identified a glycosidase hydrolase, which plays a role in sugar metabolism.…”

“…Wolbachia have also been linked with iron metabolism and storage, and this can influence key physiological traits such as fecundity [62–64]. w Flu infection induced higher levels of neuferricin, a protein that binds iron-rich heme, which is interesting given that Wolbachia produce enzymes involved in heme synthesis [38], and may utilise it as an energy source [36]. Likewise, heme is essential to the development of Plasmodium in mosquitoes [65].…”

Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont

“…The members of this genus are probably the most abundantly and vertically transmitted organisms that exist in facultative or obligate endosymbiotic associations (40). In nematodes, their prevalence is restricted to two families of worms, Onchocercidae and Pratylenchidae (41), with Onchocercidae exhibiting widespread obligate mutualism, as evidenced by retarded larval growth (42), embryostasis (43), and death (44) when the Wolbachia bacteria are eliminated.…”

Proteomic analysis of a mosquito host cell response to persistent Wolbachia infection

“…Infected cell lines further provide an in vitro approach to investigating interactions with host cells, such as control of oxidative stress [18, 19], iron metabolism [20], chromatin remodeling [21, 22] and the molecular basis for CI [23]. The C/ w Str1 cell line maintains a robust infection with the CI-inducing Wolbachia strain w Str [24, 25], which replicates in individual vacuoles surrounded by a host-derived membrane [26].…”