Intracellular bacteria are characterized by genome reduction. The 422,434–base pair genome of Buchnera aphidicola BCc, primary endosymbiont of the aphid Cinara cedri , is ∼200 kilobases smaller than the previously sequenced B. aphidicola genomes. B. aphidicola BCc has lost most metabolic functions, including the ability to synthesize the essential amino acid tryptophan and riboflavin. In addition, most retained genes are evolving rapidly. Possibly, B. aphidicola BCc is losing its symbiotic capacity and is being complemented (and might be replaced) by the highly abundant coexisting secondary symbiont.

The genome sequencing of Buchnera aphidicola BCc from the aphid Cinara cedri, which is the smallest known Buchnera genome, revealed that this bacterium had lost its symbiotic role, as it was not able to synthesize tryptophan and riboflavin. Moreover, the biosynthesis of tryptophan is shared with the endosymbiont Serratia symbiotica SCc, which coexists with B. aphidicola in this aphid. The whole-genome sequencing of S. symbiotica SCc reveals an endosymbiont in a stage of genome reduction that is closer to an obligate endosymbiont, such as B. aphidicola from Acyrthosiphon pisum, than to another S. symbiotica, which is a facultative endosymbiont in this aphid, and presents much less gene decay. The comparison between both S. symbiotica enables us to propose an evolutionary scenario of the transition from facultative to obligate endosymbiont. Metabolic inferences of B. aphidicola BCc and S. symbiotica SCc reveal that most of the functions carried out by B. aphidicola in A. pisum are now either conserved in B. aphidicola BCc or taken over by S. symbiotica. In addition, there are several cases of metabolic complementation giving functional stability to the whole consortium and evolutionary preservation of the actors involved. A critical issue in evolutionary biology is to find traits or organisms that provide evidence of the transition from one lifestyle to another, no matter how gradual the process may be. The evolutionary history of intracellular symbiosis, involving the transition of bacteria from free-living to obligate lifestyle, can reveal different types of bacteria, ranging from mere facultative to obligatory symbionts. Bacteria harboring traits of both types represent an important “missing link” in the history of this process, and that is precisely what we report here: the genome sequence and metabolic inferences of S. symbiotica from the aphid C. cedri, a bacterium that is closer to the obligate endosymbiont B. aphidicola from the aphid A. pisum than to the facultative S. symbiotica from the same aphid, whose genome has recently been sequenced. In addition, we provide metabolic evidence showing why Buchnera from C. cedri, which has lost some of the symbiotic capacities retained by other Buchnera, will not be replaced by S. symbiotica; but, conversely, both bacteria are evolving together towards the establishment of a powerful consortium with the aphid host.

Buchnera aphidicola BCc has lost its symbiotic role as the tryptophan supplier to the aphid Cinara cedri . We report the presence of a plasmid in this endosymbiont that contains the trpEG genes. The remaining genes for the pathway ( trpDCBA ) are located on the chromosome of the secondary endosymbiont “ Candidatus Serratia symbiotica.” Thus, we propose that a symbiotic consortium is necessary to provide tryptophan.

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a neglected tropical skin disease that is most commonly found in children from West and Central Africa. Despite the severity of the infection, therapeutic options are limited to antibiotics with severe side effects. Here, we show that M. ulcerans is susceptible to the anti-tubercular drug Q203 and related compounds targeting the respiratory cytochrome bc₁:aa₃. While the cytochrome bc₁:aa₃ is the primary terminal oxidase in Mycobacterium tuberculosis, the presence of an alternate bd-type terminal oxidase limits the bactericidal and sterilizing potency of Q203 against this bacterium. M. ulcerans strains found in Buruli ulcer patients from Africa and Australia lost all alternate terminal electron acceptors and rely exclusively on the cytochrome bc₁:aa₃ to respire. As a result, Q203 is bactericidal at low dose against M. ulcerans replicating in vitro and in mice, making the drug a promising candidate for Buruli ulcer treatment.

Buchnera aphidicola BCc, the primary endosymbiont of the aphid Cinara cedri (subfamily Lachninae), is losing its symbiotic capacity and might be replaced by the coresident “ Candidatus Serratia symbiotica.” Phylogenetic and morphological analyses within the subfamily Lachninae indicate two different “ Ca . Serratia symbiotica” lineages and support the longtime coevolution of both symbionts in C. cedri .