Klebsiella pneumoniae causes common and severe hospital- and community-acquired infections with a high incidence of multidrug resistance (MDR) and mortality. In this study, we investigated the ability of the antisense peptide nucleic acids (PNA) conjugated to the (KFF)3K cell-penetrating peptide (CPP) to target the gyrA KPC-producing K. pneumoniae and inhibit bacterial growth in vitro. The inhibitory effect on gyrA gene was evaluated by measuring 16s gene amplification in KPC-producing K. pneumoniae treated with the antisense PNA conjugate. The hemolytic property of the antisense PNA conjugate was accessed toward mice red blood cells. Finally, molecular modeling and dynamics simulations analyses in aqueous solutions were performed to predict the PNA conformation alone in contact with DNA (gyrA gene sequence). PNA was capable of inhibiting bacterial growth at 50 μM, also reducing 16S gene amplification in 96.7%. Besides, PNA presented low hemolytic activity (21.1% hemolysis) at this same concentration. Bioinformatics analysis demonstrated that the structure of the PNA is stable in water without major changes in its secondary structure. The ability of PNA and its conjugated CPP ((KFF)3K) to inhibit bacterial growth demonstrates the potential of this new class of antibacterial agents, encouraging further in vivo studies to confirm its therapeutic efficacy.

肺炎克雷伯菌引起常见和严重的医院和社区获得性感染，具有高发生率的多重耐药性 (MDR) 和死亡率。在这项研究中，我们研究了与 (KFF)3K 细胞穿透肽 (CPP) 结合的反义肽核酸 (PNA) 靶向产生gyr A KPC 的肺炎克雷伯菌并抑制体外细菌生长的能力。通过测定产KPC肺炎克雷伯菌的16s基因扩增来评价对gyr A基因的抑制作用用反义 PNA 偶联物处理。反义 PNA 偶联物的溶血特性可用于小鼠红细胞。最后，在水溶液中进行分子建模和动力学模拟分析，以预测单独与 DNA 接触的 PNA 构象（gyr A 基因序列）。PNA 能够在 50 μM 下抑制细菌生长，同时减少 96.7% 的 16S 基因扩增。此外，PNA 在相同浓度下表现出低溶血活性（21.1% 溶血）。生物信息学分析表明，PNA 的结构在水中是稳定的，其结构没有发生重大变化。二级结构。PNA 及其结合的 CPP ((KFF)3K) 抑制细菌生长的能力证明了这类新型抗菌剂的潜力，鼓励进一步的体内研究以确认其治疗效果。