External guide sequences ("EGS") can be used to promote RNAase P-mediated cleavage of RNA transcribed from plasmids and other genetic elements which confer drug resistance on bacterial cells. Such cleavage can render the bacteria drug sensitive. In a preferred embodiment, a vector encoding an EGS is administered to an animal or human harboring antibiotic resistant bacterial cells such that the EGS is expressed in the bacterial cells, the EGS promotes RNAase P-mediated cleavage of RNA involved in conferring antibiotic resistance to the cells, and the cells are rendered antibiotic sensitive. A preferred form of administration is via inoculation of the animal or human with cells containing genes for appropriate EGSs on promiscuous plasmids. These plasmids will spread quickly through the antibiotic-resistant population of bacterial cells, thereby making the cells susceptible to antibiotic therapy.
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