Targeting Listeria Monocytogenes rpoA and rpoD Genes Using Peptide Nucleic Acids
Targeting Listeria Monocytogenes rpoA and rpoD Genes Using Peptide Nucleic Acids
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DOI：
10.1089/nat.2013.0426
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发表时间：
2013-10-01
影响因子：
4
通讯作者：
Seleem, Mohamed N.
中科院分区：
文献类型：
--
作者：
Alajlouni, Ruba A.;Seleem, Mohamed N.
治疗细胞内病原体仍然是相当大的医学挑战，因为抗微生物剂的低效细胞内递送和细菌对被认为是最后手段的药物的治疗剂的耐药性的频繁出现。我们研究了与（KFF）（3）K细胞穿透肽缀合的反义肽核酸（PNA）靶向细胞内病原体单核细胞增生李斯特菌中RNA聚合酶α亚基（rpoA）和RNA聚合酶σ 70（rpoD）的能力。所测试的PNA显示出对L.单核细胞增多症的增长在纯培养微摩尔水平，并显着减少细胞内L。感染细胞培养物和秀丽隐杆线虫全动物模型中的单核细胞增多症。在体外，组合PNA处理是协同的，导致L.单核细胞增多症在0.5 X个别PNA浓度。这项研究证明了抗rpoA PNA作为抗菌剂的潜力，并将为改进和开发这些PNA以更好地靶向李斯特菌等细胞内病原体提供基础。本研究还建立了C. elegans作为筛选PNAs的潜在模型。
Treating intracellular pathogens remains a considerable medical challenge because of the inefficient intracellular delivery of antimicrobials and the frequent emergence of bacterial resistance to therapeutic agents deemed the drugs of last resort. We investigated the capability of antisense peptide nucleic acids (PNAs) conjugated to the (KFF)(3)K cell penetrating peptide to target RNA polymerase alpha subunit (rpoA) and RNA polymerase sigma 70 (rpoD) in the intracellular pathogen Listeria monocytogenes. The PNAs tested displayed a concentration dependent inhibition of L. monocytogenes growth in pure culture at the micromolar level and significantly reduced intracellular L. monocytogenes in infected cell culture and Caenorhabditis elegans whole animal model. In vitro, the combined PNAs treatment was synergistic resulting in a clearance of L. monocytogenes at 0.5 x the individual PNA concentration. This study demonstrates the potential of anti-rpoA PNA as an antibacterial agent and will provide the basis for improving and developing these PNAs to better target intracellular pathogens like Listeria. This study also establishes C. elegans as a potential model for the screening of PNAs.