In the province of Guayrá the Spaniards who had looked with disfavour on the Jesuits, and had enslaved the Indians when they were able, were in sore straits. The Mamelucos, finding no more Indians to enslave, fell on the two towns of Villa Rica and Ciudad Real, destroyed them utterly, and forced the inhabitants to flee for refuge into Paraguay. Thus Guayrá went the way of Matto Grosso and several other provinces of Spain, and became Portuguese. Strangely enough, most of these losses happened when Spain and Portugal were joined under one crown. At home the Spaniards and the Portuguese, however much they detested one another, were forced to keep the peace. In America they were always at war, which ended invariably to the detriment of Spain.[102] The strife begun by the Papal Bull of 1493, in which Pope Alexander VI. divided the territories discovered and to be discovered between Portugal and Spain, went on, till bit by bit Spain was stripped of the provinces of Matto Grosso, Rio Grande, and Guayrá, and found herself drawn into the numerous disputes about the Colonia del Sacramento, which cost so much blood to both contending Powers. Perhaps the most curious and interesting incident of the long struggle was the Three Years’ War, which began in 1750, after the marriage of Ferdinand VI. of Spain with Doña Barbara of Portugal. By the treaty entered into at this marriage, seven of the most flourishing of the missions situated on the left bank of the Uruguay were ceded to Portugal in exchange for La Colonia del Sacramento on the river Plate. The towns resisted change of sovereignty, as Portugal to them was typified by the Paulistas, their most inveterate enemies. The Marquis de Valdelirios in his curious despatches touches much upon this war, but perhaps the best account is to be found in the curious memoir of the Irish Jesuit Father, Tadeo Hennis,[103] who was the backbone of the resisting Guaranís.