A Tale of Three Species:Adaptation of Sodalis glossinidius to tsetse biology, Wigglesworthia metabolism and host diet

The tsetse is the insect vector for the Trypanosoma brucei parasite, the causative agent of human African trypanosomiasis. The colonisation and spread of the trypanosome correlates positively with the presence of a secondary symbiotic bacterium, Sodalis glossinidius. The metabolic requirements and interactions of the bacterium with its host are poorly understood and herein we describe a metabolic model of S. glossinidius metabolism. The model enabled the design and experimental verification of a defined medium that supports S. glossinidius growth ex vivo. This has been used subsequently to analyse in vitro aspects of S. glossinidius metabolism, revealing multiple unique adaptations of the symbiont to its environment. Continued dependence on a sugar, and the importance of the chitin monomer N-acetyl D-glucosamine as a carbon and energy source, suggests adaptation to host-derived molecules. Adaptation to the amino acid-rich blood diet is revealed by a strong dependency on L-glutamate as a source of carbon and nitrogen. Finally, the selective loss of thiamine biosynthesis, a vitamin provided to the host by the primary symbiont Wigglesworthia glossinidia, reveals an inter-symbiont dependency. The reductive evolution of S. glossinidius to exploit environmentally-derived metabolites has resulted in multiple weaknesses in the metabolic network. These may become targets for reagents that inhibit S. glossinidius growth and aid the reduction of trypanosomal transmission.