Multidrug-resistant plasmids repress chromosomally encoded T6SS to enable their dissemination.

() is a nosocomial pathogen with one of the highest rates of multidrug resistance (MDR). This is partially due to transmissible plasmids. Many strains harbor a constitutively active type VI secretion system (T6SS) that is employed to kill nonkin bacteria. T6SS and plasmid conjugation both involve cell-to-cell contact. Paradoxically, successful conjugation requires the survival of the recipient, which is the target of the T6SS. Thus, an active T6SS in either the donor or the recipient poses a challenge to plasmid conjugation. Here, we show that large conjugative MDR plasmids heavily rely on their distinctive ability to repress the T6SS of their hosts to enable their own dissemination and the conjugation of other plasmids, contributing to the propagation of MDR among isolates.