Functional insights of antibiotic resistance mechanism in Helicobacter pylori: Driven by gene interaction network and centrality-based nodes essentiality analysis. (October 2022)

• Record Type: Journal Article
• Authors: Gollapalli, Pavan; Tamizh Selvan, G.; Santoshkumar, H.S.; Ballamoole, Krishna Kumar
• Is Part Of: Microbial pathogenesis. Volume 171(2022)
• Publication Date: 2022-10
• Subjects: Gene interaction network -- Helicobacter pylori -- Antibiotic resistance -- Gene enrichment analysis; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2022.105737
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: Increased antibiotic resistance in Helicobacter pylori (H. pylori), a major human pathogen, constitutes a substantial threat to human health. Understanding the pathophysiology and development of antibiotic resistance can aid our battle with the infections caused by H. pylori . The aim of this study is to discover the high-impact key regulatory mechanisms and genes involved in antimicrobial drug resistance (AMR). In this study, we constructed a functional gene interaction network by integrating multiple sources of data related to antibiotic resistant genes (number-77) from H. pylori . The gene interaction network was assortative, with a hierarchical, scale-free topology enriched in a variety of gene ontology (GO) categories and KEGG pathways. Using an iterative clustering methodology, we identified a number of communities in the AMR gene network that comprised nine genes ( sodB, groEL, gyrA, recA, polA, tuf, infB, rpsJ, and gyrB ) that were present at the deepest level and hence were key regulators of AMR. Further, an antibiotic-resistant gene network-based centrality analysis revealed superoxide dismutase ( sodB) as a bottleneck node in the network. Our findings suggested that sodB is critically enriched in the cellular response to oxidative stress, removal of superoxide radicals, cellular oxidant detoxification processes, cellular component biogenesis, response to reactive oxygen species, urea metabolic process, nitrogen cycle metabolic process and reactive oxygen species metabolic process. We demonstrated how the sodB, which are involved in the response to reactive oxygen species, urea metabolic process, nitrogen cycle metabolic process, reactive oxygen species metabolic process, regulated by Fur gene/proteins, claim a major authority over regulation and signal propagation in the AMR. Graphical abstract: Image 1 Highlights: Discover the high-impact key regulatory mechanisms and genes involved in the antimicrobial drug resistance. Identified key regulatory gene in the AMR gene network (SodB, groEL, gyrA, recA, polA, tuf, infB, rpsJ, and gyrB). Network-based centrality analysis revealed that superoxide dismutase (SodB) as a bottleneck node in the network. SodB is significantly enriched during processes of superoxide elimination and detoxification in response to oxidative stress.