Prachi Sao1, Siddharth Vats2, Sachidanand Singh3. 1. Faculty of Biotechnology, Institute of Biosciences and Technology, Shri Ramswaroop Memorial University, Barabanki, Uttar Pradesh 225003, India. Electronic address: prachi1627@gmail.com. 2. Faculty of Biotechnology, Institute of Biosciences and Technology, Shri Ramswaroop Memorial University, Barabanki, Uttar Pradesh 225003, India. Electronic address: Vatssidd@gmail.com. 3. 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. Electronic address: drsachinbioinfo@gmail.com.
Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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.
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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.