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The interplay of multiple feedback loops with post-translational kinetics results in bistability of mycobacterial stress response.

ABSTRACT: Bacterial persistence is the phenomenon in which a genetically identical fraction of a bacterial population can survive exposure to stress by reduction or cessation of growth. Persistence in mycobacteria has been recently linked to a stress-response network, consisting of the MprA/MprB two-component system and alternative sigma factor sigma(E). This network contains multiple positive transcriptional feedback loops which may give rise to bistability, making it a good candidate for controlling the mycobacterial persistence switch. To analyze the possibility of bistability, we develop a method that involves decoupling of the network into transcriptional and post-translational interaction modules. As a result we reduce the dimensionality of the dynamical system and independently analyze input-output relations in the two modules to formulate a necessary condition for bistability in terms of their logarithmic gains. We show that neither the positive autoregulation in the MprA/MprB network nor the sigma(E)-mediated transcriptional feedback is sufficient to induce bistability in a biochemically realistic parameter range. Nonetheless, inclusion of the post-translational regulation of sigma(E) by RseA increases the effective cooperativity of the system, resulting in bistability that is robust to parameter variation. We predict that overexpression or deletion of RseA, the key element controlling the ultrasensitive response, can eliminate bistability.

SUBMITTER: Tiwari A

PROVIDER: S-EPMC3543150 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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The interplay of multiple feedback loops with post-translational kinetics results in bistability of mycobacterial stress response.

Tiwari Abhinav A Balázsi Gábor G Gennaro Maria Laura ML Igoshin Oleg A OA

Physical biology 20100823 3

Bacterial persistence is the phenomenon in which a genetically identical fraction of a bacterial population can survive exposure to stress by reduction or cessation of growth. Persistence in mycobacteria has been recently linked to a stress-response network, consisting of the MprA/MprB two-component system and alternative sigma factor sigma(E). This network contains multiple positive transcriptional feedback loops which may give rise to bistability, making it a good candidate for controlling the ...[more]

PMID: 20733247

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Project description:The impact of climate change entails a progressive and inexorable modification of the Earth's climate and events such as salinity, drought, extreme temperatures, high luminous intensity and ultraviolet radiation tend to be more numerous and prolonged in time. Plants face their exposure to these abiotic stresses or their combination through multiple physiological, metabolic and molecular mechanisms, to achieve the long-awaited acclimatization to these extreme conditions, and to thereby increase their survival rate. In recent decades, the increase in the intensity and duration of these climatological events have intensified research into the mechanisms behind plant tolerance to them, with great advances in this field. Among these mechanisms, the overproduction of molecular reactive species stands out, mainly reactive oxygen, nitrogen and sulfur species. These molecules have a dual activity, as they participate in signaling processes under physiological conditions, but, under stress conditions, their production increases, interacting with each other and modifying and-or damaging the main cellular components: lipids, carbohydrates, nucleic acids and proteins. The latter have amino acids in their sequence that are susceptible to post-translational modifications, both reversible and irreversible, through the different reactive species generated by abiotic stresses (redox-based PTMs). Some research suggests that this process does not occur randomly, but that the modification of critical residues in enzymes modulates their biological activity, being able to enhance or inhibit complete metabolic pathways in the process of acclimatization and tolerance to the exposure to the different abiotic stresses. Given the importance of these PTMs-based regulation mechanisms in the acclimatization processes of plants, the present review gathers the knowledge generated in recent years on this subject, delving into the PTMs of the redox-regulated enzymes of plant metabolism, and those that participate in the main stress-related pathways, such as oxidative metabolism, primary metabolism, cell signaling events, and photosynthetic metabolism. The aim is to unify the existing information thus far obtained to shed light on possible fields of future research in the search for the resilience of plants to climate change.

Dataset Information

The interplay of multiple feedback loops with post-translational kinetics results in bistability of mycobacterial stress response.

Publications

The interplay of multiple feedback loops with post-translational kinetics results in bistability of mycobacterial stress response.

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