A Network Biology Approach to Decipher Stress Response in Bacteria UsingEscherichia coliAs 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.

A first perturbome ofPseudomonas aeruginosa: Identification of core genes related to multiple perturbations by a machine learning approach

“…Similar results, regarding enriched pathways, have been obtained in other studies with eukaryotic models, including disturbed human cell lines [4,5,56], Arabidopsis thaliana under physical and genotoxic stresses [2], or a genome-wide association study of a generic response to stress conditions [6]. In the case of prokaryotic organisms, two studies have used Escherichia coli as a model to identify differentially expressed genes after exposure to stress conditions [3] and to create networks associated with the response to fluctuating environments [7]. Differences with other organisms and disturbances can suggest that response cell stress can be organismal specific, although heterogeneity has also been suggested as a reasonable explanation because of differences in the response in a homogeneous cell population [56,75].…”

“…This corresponds with the global profiles of expression of 46 core response genes. Also, regulation of lipid metabolism is relevant for survival in the wide range of environmental conditions where bacteria thrive [72], even for biofilm-living forms [3] as P.…”

A Research on The Role of RpoS againts pH Stress and Metals in Escherichia coli

“…Spor veya biyofilm gibi çevresel koşullara karşı dirençli yapılar oluşturamayan mikroorganizmalar, bulundukları doğal ortamlarda açlık, pH, sıcaklık, ozmolarite ve toksik kimyasal maddeler gibi birçok stres faktörü ile aynı anda başa çıkmak zorundadırlar. Bu nedenle yaşam için oldukça kompleks regülatör ağlar oluşması ve bir çok mekanizmanın bir denge içinde çalışması gerektiği düşünülmektedir [3]. Bu sebeple de kompleks regülatör ağlarda görev alan genlerin ve fonksiyonlarının belirlenmesi hem bakteriyal yaşam hemde onlarla mücadele açısından oldukça önemlidir.…”

“…Metal ve pH stresi doğada en sık karşılaşılan streslerden ikisidir. Bu streslere karşı tekli veya operon olarak düzenlenen korunma mekanizmaları olduğu gibi kompleks ağlar şeklinde birçok genin rolü ile de korunma sağlanmaktadır [3].…”

Tackling microbial threats in agriculture with integrative imaging and computational approaches

“…A major application of high-throughput pathogen screenings are measurements of fungicide sensitivity, which is relevant for the early detection of resistance mutations at the regional or continental scale [119] . More broadly, stress response assessments of fungal and bacterial pathogens can provide important clues about the expression of virulence factors, multi-drug resistance, biofilm formation, and antimicrobial resistance [117] , [120] . This is because stress induced in in vitro setups can share similarities with infection stress conditions.…”