The emergence of carbapenem-resistant Klebsiella Pneumoniae had been reported previously, which needs rapid attention. Currently, Pittsburgh University Hospital reported a new strain of carbapenem-resistant Klebsiella pneumoniae that was co-producing OXA-232 and NDM-1 named as PittNDM01. This strain is resistant to almost all beta-lactam antibiotics such as Carbapenem as well as to fluoroquinolones and aminoglycosides. Globally, failure to the wide-spread pathogenic strains had been observed due to the increased and antibiotic resistance, which leads to less antimicrobial drug efficacy. Since last decades, computational genomic approaches have been introduced to fight against resistant pathogens, which is an advanced approach for novel drug targets investigation. The current study emphasizes the utilization of the available genomic and proteomic data of Klebsiella pneumoniae PittNDM01 for the identification of novel drug targets for future drug developments. Comparative genomic analysis and molecular biological tools were applied, results in observing 582 non-human homologous-essential proteins of Klebsiella pneumoniae. Among the total 582 proteins, 66 were closely related to the pathogen-specific pathway. Out of all 66-targeted proteins, ten non-homologous essential proteins were found to have druggability potential. The subcellular localization of these proteins revealed; 6 proteins in the cytoplasm, 2 in the inner membrane, and one each in periplasmic space and outer membrane. All the above 10 proteins were compared to the proteins sequences of gut flora to eliminate the homologous proteins. In total, 6-novel non-human and non-gut flora essential drug targets of Klebsiella pneumoniae PittNDM01 strain were identified. Further, the 3D structures of the identified drug target proteins were developed, and protein-protein interaction network analysis was performed to know the functional annotation of the desire proteins. Therefore, these non-homologous essential targets ensure the survival of the pathogen and hence can be targeted for drug discovery.

中文翻译：

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计算减性基因组分析，用于表征肺炎克雷伯菌菌株PittNDM01中的新型药物靶标。

先前已经报道了耐碳青霉烯的肺炎克雷伯菌的出现，需要引起高度重视。目前，匹兹堡大学医院报告了一种新的耐碳青霉烯的肺炎克雷伯氏菌菌株，它是共同生产的OXA-232和NDM-1，名为PittNDM01。该菌株对几乎所有的β-内酰胺抗生素（如碳青霉烯）以及氟喹诺酮类和氨基糖苷类都有抗药性。在全球范围内，由于增加的抗药性和耐药性，观察到了对广泛传播的致病菌株的破坏，这导致了较低的抗菌药物功效。自从过去的几十年以来，已经引入了计算基因组方法来对抗耐药性病原体，这是新型药物靶标研究的一种先进方法。当前的研究强调利用肺炎克雷伯氏菌PittNDM01的可用基因组和蛋白质组学数据来鉴定用于未来药物开发的新药物靶标。应用比较基因组分析和分子生物学工具，结果观察到了582个非人类肺炎克雷伯菌的必需蛋白质。在582种蛋白质中，有66种与病原体特异性途径密切相关。在所有66种靶向蛋白质中，发现有10种非同源必需蛋白质具有可药性。这些蛋白质的亚细胞定位揭示了；细胞质中有6种蛋白质，内膜中有2种蛋白质，周质空间和外膜中各一种。将以上所有10种蛋白质与肠道菌群的蛋白质序列进行比较，以消除同源蛋白质。总共，鉴定了肺炎克雷伯菌PittNDM01菌株的6种新型非人类和非肠道菌群基本药物靶标。此外，开发了已鉴定的药物靶蛋白的3D结构，并进行了蛋白-蛋白相互作用网络分析以了解所需蛋白的功能注释。因此，这些非同源的必需靶标确保了病原体的存活，因此可以作为药物发现的靶标。