Inhibition of Escherichia coli viability by external guide sequences complementary to two essential genes.
Narrow spectrum antimicrobial activity has been designed to reduce the expression of two essential genes, one coding for the protein subunit of RNase P (C5 protein) and one for gyrase (gyrase A). In both cases, external guide sequences (EGS) have been designed to complex with either mRNA. Using the EGS technology, the level of microbial viability is reduced to less than 10% of the wild-type strain. The EGSs are additive when used together and depend on the number of nucleotides paired when attacking gyrase A mRNA. In the case of gyrase A, three nucleotides unpaired out of a 15-mer EGS still favor complete inhibition by the EGS but five unpaired nucleotides do not.
McKinney
J
J
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Guerrier-Takada
C
C
Wesolowski
D
D
Altman
S
S
D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004722:Endoribonucleases / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics* / Q000502:physiology; D029968:Escherichia coli Proteins; D005798:Genes, Bacterial / Q000502:physiology*; D008969:Molecular Sequence Data; D016337:RNA, Catalytic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism; D043262:Ribonuclease P
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D016337:RNA, Catalytic; D012333:RNA, Messenger; D012343:RNA, Transfer; D004722:Endoribonucleases; D043262:Ribonuclease P; C470865:ribonuclease P, E coli; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II