Inhibition of bacterial translation and growth by peptide nucleic acids targeted to domain II of 23S rRNA.
The objective of this work was to study the inhibitory effects of antisense peptide nucleic acids (PNAs) targeted to domain II of 23S rRNA on bacterial translation and growth. In this paper, we report that PNA(G1138) or peptide-PNA(G1138) targeted to domain II of 23S rRNA can inhibit both translation in vitro (in a cell-free translation system) and bacterial growth in vivo. The inhibitory concentration (IC50) and the minimum inhibiting concentration (MIC) are 0.15 and 10 microM, respectively. The inhibition effect of PNA(G1138) in vitro is somewhat lower than that of tetracycline (IC50 = 0.12 microM), but the MIC of peptide-PNA(G1138) against Escherichia coli is significantly higher than that of tetracycline (MIC = 4 microM). Further studies based on similar colony-forming unit (CFU) assays showed that peptide-PNA(G1138) at 10 microM is bactericidal, but the bactericidal effect is less effective than that of tetracycline. Nevertheless, the results demonstrated that the peptide-PNA(G1138) treatment is bactericidal in a dose- and sequence-dependent manner and that the G1138 site of 23S rRNA is a possible sequence target for designing novel PNA-based antibiotics.
Xue-Wen
Huang
H
Department of pathogenic organisms, Preclinical medicine college, Suzhou university, Suzhou 215123, China.
Jie
Pan
P
Xian-Yuan
An
A
Hong-Xiang
Zhuge
Z
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002474:Cell-Free System; D015169:Colony Count, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D005453:Fluorescence; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D020135:Peptide Nucleic Acids / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects*; D012338:RNA, Ribosomal, 23S / Q000187:drug effects*; D013462:Sulfur Radioisotopes
D000900:Anti-Bacterial Agents; D016375:Antisense Elements (Genetics); D020135:Peptide Nucleic Acids; D012338:RNA, Ribosomal, 23S; D013462:Sulfur Radioisotopes; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D008715:Methionine