Conference
Book of abstracts: 5th Belgrade Bioinformatics Conference, Serbia, Belgrade,17-20 june 2024.
العنوان: | Book of abstracts: 5th Belgrade Bioinformatics Conference, Serbia, Belgrade,17-20 june 2024. |
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المؤلفون: | Marković, Sofija, Đorđević, Magdalena, Ou, Hong-Yu, Đorđević, Marko |
المساهمون: | Morić, Ivana, Đorđević, Valentina |
المصدر: | 5th Belgrade Bioinformatics Conference |
بيانات النشر: | Institute of Molecular Genetics and Genetic Engineering |
سنة النشر: | 2024 |
مصطلحات موضوعية: | antibiotic persistence, toxin-antitoxin systems, bistability, bifurcations, stochastic simulations |
الوصف: | Antibiotic persistence refers to a phenomenon where a subset of genetically identical bacteria enters a dormant state, becoming highly resistant to environmental stresses. This phenomenon is crucial in understanding why biofilms, communities of bacteria attached to surfaces, often resist antibiotic treatments, leading to persistent and recurrent infections. Despite being recognized for almost a century, the precise processes triggering persister formation remain elusive. Among the various biological systems implicated in persister formation, toxin-antitoxin systems within bacteria stand out. These systems consist of a toxic protein and its corresponding antitoxin, which neutralizes the toxin’s effects. In this study, we propose a biophysical model focusing on a type I toxin-antitoxin system where the antitoxin is a small RNA molecule. Our analysis involves both theoretical calculations and computer simulations to explore the stability of the model and its behavior under deterministic and stochastic conditions. Our model successfully reproduces two distinct states within bacterial populations: a low-toxin state associated with normal growth and a high-toxin state leading to persister formation. We analytically derive a system stability diagram, allowing us to map under which conditions the low and high toxin states coexist in an isogenic bacterial population. Furthermore, we observe a stochastic transition from low to high-toxin. This bistability in our model arises from feedback loops governing toxin production. Specifically, a positive feedback loop controls toxin dilution rate, while a negative feedback loop slows down antitoxin degradation. Our findings have significant implications for understanding bacterial persistence mechanisms. We have shown that type I toxin-antitoxin systems may play a role in stressinduced persister formation. However, they are unlikely to account for “spontaneous” persister formation, as toxin expression is markedly reduced during normal growth phases. These insights could lead to ... |
نوع الوثيقة: | conference object |
اللغة: | English |
Relation: | info:eu-repo/grantAgreement/ScienceFundRS/Ideje/7750294/RS//; www.belbi.bg.ac.rs; https://imagine.imgge.bg.ac.rs/handle/123456789/2738; https://hdl.handle.net/21.15107/rcub_imagine_2738 |
الاتاحة: | https://imagine.imgge.bg.ac.rs/handle/123456789/2738 https://imagine.imgge.bg.ac.rs/bitstream/id/846521/BelBi2024-Book-of-Abstracts_1-16,79,141-142.pdf https://hdl.handle.net/21.15107/rcub_imagine_2738 |
Rights: | openAccess ; https://creativecommons.org/licenses/by-nc-nd/4.0/ ; BY-NC-ND ; © 2024 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade |
رقم الانضمام: | edsbas.A57603F9 |
قاعدة البيانات: | BASE |
الوصف غير متاح. |