A Bacterial Shortcut to Amyloidosis
| Autor: | María Moreno-del Álamo, Alicia Sánchez-Gorostiaga, María Fernández, Rafael Giraldo, Aída Alonso-del Valle, Juan Nogales, Pedro Botías, Jesús García-Cantalejo, Laura Molina-García, Zaira Martín-Moldes |
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| Přispěvatelé: | European Commission, Consejo Superior de Investigaciones Científicas (España), CSIC - Unidad de Recursos de Información Científica para la Investigación (URICI) |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Amyloid 030106 microbiology Systems analysis model amyloid disease ROS toxicity Membrane targeting Biology medicine.disease_cause Microbiology Bacterial cell structure 03 medical and health sciences Amyloid disease Model amyloid disease Escherichia coli medicine Transcription factor Original Research amyloid proteinopathy systems analysis Amyloid proteinopathy membrane targeting biology.organism_classification 030104 developmental biology Biochemistry prionoid Intracellular Oxidative stress Bacteria Prionoid |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Frontiers in Microbiology |
| ISSN: | 1664-302X |
| DOI: | 10.3389/fmicb.2017.00539 |
| Popis: | 21 p.-10 fig. The synthetic bacterial prionoid RepA-WH1 causes a vertically transmissible amyloid proteinopathy in Escherichia coli that inhibits growth and eventually kills the cells. Recent in vitro studies show that RepA-WH1 builds pores through model lipid membranes, suggesting a possible mechanism for bacterial cell death. By comparing acutely (A31V) and mildly (ΔN37) cytotoxic mutant variants of the protein, we report here that RepA-WH1(A31V) expression decreases the intracellular osmotic pressure and compromise bacterial viability under either aerobic or anaerobic conditions. Both are effects expected from threatening membrane integrity and are in agreement with findings on the impairment by RepA-WH1(A31V) of the proton motive force (PMF)-dependent transport of ions (Fe3+) and ATP1 synthesis. Systems approaches reveal that, in aerobiosis, the PMF-independent respiratory dehydrogenase NdhII is induced in response to the reduction in intracellular levels of iron. While NdhII is known to generate H2O2 as a by-product of the autoxidation of its FAD cofactor, key proteins in the defense against oxidative stress (OxyR, KatE), together with other stress-resistance factors, are sequestered by co-aggregation with the RepA-WH1(A31V) amyloid. Our findings suggest a route for RepA-WH1 toxicity in bacteria: a primary hit of damage to the membrane, compromising bionergetics, triggers a stroke of oxidative stress, which is exacerbated due to the aggregation-dependent inactivation of enzymes and transcription factors that enable the cellular response to such injury. The proteinopathy caused by the prion-like protein RepA-WH1 in bacteria recapitulates some of the core hallmarks of human amyloid diseases. This work has been supported by grants from Spanish AEI / EU-FEDER (BIO2012-30852, BIO2015- 68730-R and CSD2009-00088) and CSIC (i-LINK0889) to R.G. We acknowledge support of the publication fee by the CSIC Open Access Support Initiative through its Unit of Information Resources for Research (URICI). |
| Databáze: | OpenAIRE |
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