Phage WO of Wolbachia: lambda of the endosymbiont world

Abstract

The discovery of an extraordinarily high level of mobile elements in the genome of Wolbachia, a widespread arthropod and nematode endosymbiont, suggests that this bacterium could be an excellent model for assessing the evolution and function of mobile DNA in specialized bacteria. In this paper, we discuss how studies on the temperate bacteriophage WO of Wolbachia have revealed unexpected levels of genomic flux and are challenging previously held views about the clonality of obligate intracellular bacteria. We also discuss the roles this phage might play in the Wolbachia-arthropod symbiosis and infer how this research can be translated to combating human diseases vectored by arthropods. We expect that this temperate phage will be a preeminent model system to understand phage genetics, evolution and ecology in obligate intracellular bacteria. In this sense, phage WO might be likened to phage lambda of the endosymbiont world.

Figure 1

Horizontal transfer of bacteriophage WO. (a) Phage WO can transfer between two different Wolbachia strains that coinfect the same host cell [22,23,25,31]. The phage becomes lytic (i) and lyses its Wolbachia host cell (ii). An active phage particle then attaches to a phage-free Wolbachia that coinfects the same host cell (iii) and injects its DNA (iv), at which point the DNA integrates into the chromosome (v). (b) Phage WO might also, hypothetically, be transmitted paternally by sperm from an infected male to the egg of a female carrying a phage-free Wolbachia. Once the sperm fertilizes the egg (i) the transported phage is released (ii) and can infect Wolbachia as in steps (iii-v) above.

Figure 2

The genome architecture of phage WO. WOCauB2 from wCauB is an active phage based on the detection of excised intermediates by inverse PCR and genome sequencing [29]. Its genome is 43 Kb in size and encodes 47 genes (numbered from gp1 to gp47). Functional gene homologs include a site-specific recombinase gene (teal), head region genes (purple), baseplate assembly genes (pink), tail protein genes (green), and a phage late control gene (red). Other interesting genes of note encode homologs of plasmid replication protein RepA and a sigma-70 transcription factor (grey). Several of the encoded proteins might interact with host proteins, including a patatin-like protein, VrlC.1 and VrlC.2 (orange), and ankyrin-repeat proteins (ANK, blue). Genes of unknown function are shown in white, and transposase (Tp) is shown in yellow.

Figure 3

The phage density model of cytoplasmic incompatibility (CI). (a) When phage WO is lysogenic and titers of Wolbachia are high in male reproductive tissues, high levels of CI prevent the production of viable offspring after mating with an uninfected female. (b) When phage WO in these Wolbachia becomes lytic, Wolbachia cell titers decrease due to cell lysis and cause the infected male and uninfected female to produce an increased number of offspring [27].