Describe is a method for screening
mutant prokaryotic cells to identify producers of a cytotoxic agent active against a target
cell, the method comprising the steps of: (a) providing cells of a producer prokaryotic species; (b) generating a
pool of
mutant producer cells by transposon
mutagenesis of the cells of step (a) with an activating transposon (TnA), wherein the TnA comprises an outward-facing
promoter (TnAP) capable of increasing transcription of a
gene at or near its
insertion site in the
DNA of said producer cells; (c) co-encapsulating individual members of the
pool of step (b) with one or more target cells in microdroplets, the microdroplets comprising a volume of aqueous growth media suspended in an immiscible carrier liquid, thereby generating a
library of microdroplets each comprising a single
mutant producer
cell and one or more target
cell(s); (d) incubating the microdroplet
library of step (c) under conditions suitable for co-culture of the single mutant producer cell and target cell(s) to produce a
library of microcultures, whereby mutant producer cells producing a cytotoxic agent active against the target cell(s) outgrow target cells in each
microculture; and (e) screening the library of microcultures of step (d) for microcultures in which target cells have been outgrown or overgrown to
extinction by mutant producer cells.