Slender and stumpy bloodstream forms of Trypanosoma brucei display a differential response to extracellular acidic and proteolytic stress

Natural infections of mammals with African trypanosomes, such as Trypanosom a brucei, are generally pleomorphic, the population consisting of different forms, termed slender and stumpy forms, that vary in number as the parasit aemia develops. We show that the differentiation of slender into stumpy for ms is characterized by the acquisition by the parasite of the ability to re gulate its internal pH, even in the face of a large, inwardly directed grad ient of H+, as well as a tolerance towards external proteolytic stress. The se adaptations effectively abbrogate cellular stress-activated signalling p athways involving adenylate cyclase and glycosylphosphoinositol-specific ph ospholipase-C mediated release of the surface coat. Although in metabolic t erms stumpy forms of the parasite are considered to be preadapted to life i n the arthropod vector, these data clearly demonstrate that these forms als o possess additional cellular adaptations designed to deal with the immedia te and potentially harmful changes in the extracellular environment that oc cur upon ingestion of a bloodmeal by the tsetse fly vector.