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DNA Enzyme Generated by a Novel Single-Stranded DNA Expression Vector Inhibits Expression of the Essential Bacterial Cell Division Gene ftsZ
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文摘
Rapid emergence of antibiotic-resistant bacterial pathogens has created urgent demand for thediscovery and development of new antibacterial agents directed toward novel targets. Antisenseoligodeoxynucleotides (AS-ODN) and their modified forms have been utilized to block gene expressionin bacterial cells, showing potential for developing highly specific and efficacious antibacterial agents. Inthis study, a tetracycline-regulated expression vector was developed for generating single-stranded DNA(ssDNA) of a desired target sequence in bacterial cells. This inducible ssDNA expression vector wastested for producing a DNA enzyme designed to specifically cleave ftsZ mRNA. Our results indicate thatthe expressed DNA enzyme molecules not only repress ftsZ gene expression and but also inhibit bacterialcell proliferation. Although we believe that the cleavage of ftsZ mRNA by the expressed DNA enzymemolecules is responsible for the inhibitory effects on ftsZ gene expression and bacterial cell proliferation,the antisense mechanism could also be responsible for the biological effects. The ability of this ssDNAexpression system to selectively modulate gene expression may provide a powerful strategy in determiningthe contribution of a given gene product to bacterial growth or pathogenesis and opens a new venue fordeveloping antibacterial agents.

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