title: A Network Biology Approach to Decipher Stress Response in Bacteria Using Escherichia coli As a Model.
abstract: The development of drug-resistant pathogenic bacteria poses challenges to global health for their treatment and control. In this context, stress response enables bacterial populations to survive extreme perturbations in the environment but remains poorly understood. Specific modules are activated for unique stressors with few recognized global regulators. The phenomenon of cross-stress protection strongly suggests the presence of central proteins that control the diverse stress responses. In this work, Escherichia coli was used to model the bacterial stress response. A Protein-Protein Interaction Network was generated by integrating differentially expressed genes in eight stress conditions of pH, temperature, and antibiotics with relevant gene ontology terms. Topological analysis identified 24 central proteins. The well-documented role of 16 central proteins in stress indicates central control of the response, while the remaining eight proteins may have a novel role in stress response. Cluster analysis of the generated network implicated RNA binding, flagellar assembly, ABC transporters, and DNA repair as important processes during response to stress. Pathway analysis showed crosstalk of Two Component Systems with metabolic processes, oxidative phosphorylation, and ABC transporters. The results were further validated by analysis of an independent cross-stress protection dataset. This study also reports on the ways in which bacterial stress response can progress to biofilm formation. In conclusion, we suggest that drug targets or pathways disrupting bacterial stress responses can potentially be exploited to combat antibiotic tolerance and multidrug resistance in the future.
authors.affiliation: 1 Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology , New Delhi, India .
authors.forename: Shashwat Deepali
authors.initials: SD
authors.lastname: Nagar
authors.affiliation: 1 Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology , New Delhi, India .
authors.forename: Bhavye
authors.initials: B
authors.lastname: Aggarwal
authors.affiliation: 1 Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology , New Delhi, India .|2 Laboratory of Molecular Biology and Genetic Engineering, School of Biotechnology, Jawaharlal Nehru University , New Delhi, India .
authors.forename: Shikha
authors.initials: S
authors.lastname: Joon
authors.affiliation: 2 Laboratory of Molecular Biology and Genetic Engineering, School of Biotechnology, Jawaharlal Nehru University , New Delhi, India .
authors.forename: Rakesh
authors.initials: R
authors.lastname: Bhatnagar
authors.affiliation: 1 Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology , New Delhi, India .
authors.forename: Sonika
authors.initials: S
authors.lastname: Bhatnagar
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria; D018441:Biofilms / Q000254:growth & development*; D016000:Cluster Analysis; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology; D053263:Gene Regulatory Networks; D006863:Hydrogen-Ion Concentration; D060066:Protein Interaction Maps; D013312:Stress, Physiological; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents