Faculty of Biotechnology, Institute of Biosciences and Technology, Shri Ramswaroop Memorial University, Barabanki, Uttar Pradesh 225003, India.
Faculty of Biotechnology, Institute of Biosciences and Technology, Shri Ramswaroop Memorial University, Barabanki, Uttar Pradesh 225003, India; Department of Biotechnology, Vignan's Foundation for Science, Technology and Research (Deemed to be University), Vadlamudi, Guntur 522213, Andhra Pradesh, India; Department of Biotechnology, Smt. S. S. Patel Nootan Science & Commerce College, Sankalchand Patel University, Visnagar 384315, Gujarat, India.
Gene. 2022 Sep 25;839:146734. doi: 10.1016/j.gene.2022.146734. Epub 2022 Jul 11.
The gram-negative bacteria Porphyromonas gingivalis (PG) is the most prevalent cause of periodontal diseases and multidrug-resistant (MDR) infections. Periodontitis and MDR infections are severe due to PG's ability to efflux antimicrobial and virulence factors. This gives rise to colonisation, biofilm development, evasion, and modulation of the host defence system. Despite extensive studies on the MDR efflux pump in other pathogens, little is known about the efflux pump and its association with the virulence factor in PG. Prolonged infection of PG leads to complete loss of teeth and other systemic diseases. This necessitates the development of new therapeutic interventions to prevent and control MDR.
The study aims to identify the most indispensable proteins that regulate both resistance and virulence in PG, which could therefore be used as a target to fight against the MDR threat to antibiotics.
We have adopted a hierarchical network-based approach to construct a protein interaction network. Firstly, individual networks of four major efflux pump proteins and two virulence regulatory proteins were constructed, followed by integrating them into one. The relationship between proteins was investigated using a combination of centrality scores, k-core network decomposition, and functional annotation, to computationally identify the indispensable proteins.
Our study identified four topologically significant genes, PG_0538, PG_0539, PG_0285, and PG_1797, as potential pharmacological targets. PG_0539 and PG_1797 were identified to have significant associations between the efflux pump and virulence genes. This type of underpinning research may help in narrowing the drug spectrum used for treating periodontal diseases, and may also be exploited to look into antibiotic resistance and pathogenicity in bacteria other than PG.
革兰氏阴性细菌牙龈卟啉单胞菌（PG）是牙周病和多药耐药（MDR）感染最常见的原因。由于 PG 能够外排抗菌和毒力因子，牙周炎和 MDR 感染较为严重。这导致了定植、生物膜的发展、逃避和宿主防御系统的调节。尽管对其他病原体的 MDR 外排泵进行了广泛的研究，但对于 PG 中的外排泵及其与毒力因子的关联知之甚少。PG 的长期感染会导致牙齿完全丧失和其他全身疾病。这就需要开发新的治疗干预措施来预防和控制 MDR。
本研究旨在确定调节 PG 中耐药性和毒力的最不可或缺的蛋白质，这些蛋白质可以作为对抗抗生素 MDR 威胁的靶点。
我们采用了基于层次网络的方法来构建蛋白质相互作用网络。首先，构建了四个主要外排泵蛋白和两个毒力调节蛋白的单独网络，然后将它们整合到一个网络中。使用中心性评分、k 核网络分解和功能注释的组合来研究蛋白质之间的关系，以计算识别不可或缺的蛋白质。
我们的研究确定了四个拓扑上重要的基因，PG_0538、PG_0539、PG_0285 和 PG_1797，作为潜在的药理靶点。PG_0539 和 PG_1797 被鉴定为在外排泵和毒力基因之间具有显著的关联。这种基础性研究可能有助于缩小用于治疗牙周病的药物谱，也可能被利用来研究除 PG 以外的细菌中的抗生素耐药性和致病性。
