Metabolic and regulatory engineering of : mimicking phage-mediated horizontal acquisition of antibiotic biosynthesis and quorum-sensing capacities Free

Abstract

is an important cause of opportunistic human infections. Many, but not all, strains produce prodigiosin, a secondary metabolic, red-pigment antibiotic, the biosynthesis of which is directed by the gene cluster. Quorum sensing (QS) involves the production and detection of chemical signal molecules as a means to regulate gene expression in response to population cell density. Several strains of have previously been shown to possess an -acyl--homoserine lactone (aHSL) QS system. This study aimed to determine the impact of introducing, by phage-mediated horizontal gene transfer, a biosynthetic gene cluster () and a regulatory locus (aHSL QS) into strains lacking the respective trait. The cluster from ATCC 274 ( 274) was transferred to the non-pigmented strain, strain 12 ( 12). In the engineered strain, pigment was expressed and brought under the control of the recipient's native regulatory systems (aHSL QS and ). Moreover, transfer of the aHSL locus from 12 to the non-QS 274 resulted in the imposition of aHSL control onto a variety of native traits, including pigment production. In addition, during this study, the QS regulon of the clinical strain, 12, was characterized, and some novel QS-regulated traits in were identified. The results have implications for the evolution and dissemination of biosynthetic and QS loci, illustrating the genetic modularity and ease of acquisition of these traits and the capacity of phages to act as vectors for horizontal gene transfer.

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2006-07-01
2024-03-29
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