MAP kinase kinase 1 (MKK1) is essential for transmission of Trypanosoma brucei by Glossina morsitans

MAP kinase kinase 1 (MKK1) is encoded by a single copy gene in Trypanosoma brucei. It has been shown recently that MKK1 is not essential for bloodstream forms [14]. To investigate the requirement for MKK1 in other life-cycle stages we generated null mutants in procyclic forms of a fly-transmissible strain. These grew normally in culture and were able to establish midgut infections in tsetse at normal rates and intensities, but were incapable of colonising the salivary glands. Transformation of null mutants with an ectopic copy of MKK1 enabled parasites to complete the life cycle in tsetse and infect mice. This is the first example of a gene that is indispensable for transmission of T. brucei. It also raises the possibility that activating the MKK1 signalling cascade in vitro might trigger the differentiation and proliferation of life-cycle stages of T. brucei that are currently refractory to culture.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (70 K)Download as PowerPoint slideHighlights► Generation of MKK1 null mutants in a fly-transmissible strain. ► No overt phenotype of null mutant as procyclic forms. ► Null mutants established normal midgut infections in tsetse. ► Null mutants were not capable of colonising the fly salivary glands. ► Add-back mutant was able to complete the life cycle in tsetse and infect mice.