The expression of integron arrays is shaped by the translation rate of cassettes
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2024
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Springer Nature
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Carvalho, A., Hipólito, A., Trigo da Roza, F., García-Pastor, L., Vergara, E., Buendía, A., García-Seco, T., & Escudero, J. A. (2024). The expression of integron arrays is shaped by the translation rate of cassettes. Nature communications, 15(1), 9232. https://doi.org/10.1038/s41467-024-53525-6
Abstract
Integrons are key elements in the rise and spread of multidrug resistance in Gram-negative bacteria. These genetic platforms capture cassettes containing promoterless genes and stockpile them in arrays of variable length. In the current integron model, expression of cassettes is granted by the Pc promoter in the platform and is assumed to decrease as a function of its distance. Here we explored this model using a large collection of 136 antibiotic resistance cassettes and show the effect of distance is in fact negligible. Instead, cassettes have a strong impact in the expression of downstream genes because their translation rate affects the stability of the whole polycistronic mRNA molecule. Hence, cassettes with reduced translation rates decrease the expression and resistance phenotype of cassettes downstream. Our data puts forward an integron model in which expression is contingent on the translation of cassettes upstream, rather than on the distance to the Pc.
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Acknowledgements:
We would like to thank José R. Penadés for the helpful discussions and for the critical reading of the manuscript. We are grateful to all the members of the MBA lab for the helpful discussion. The work in the MBA laboratory is supported by the European Research Council (ERC) through a Starting Grant [ERC grant no. 803375-KRYPTONINT] and the Ministerio de Ciencia e Innovación [PID2020-117499RB-100 and CNS2022-135857]; J.A.E. has been supported by the Atracción de Talento Program of the Comunidad de Madrid [2016-T1/BIO-1105 and 2020-5A/BIO19726]; A.H. is supported by the PhD program at UCM; F.T.R. is supported by the Portuguese Fundação para Ciência e a Tecnologia [SFRH/BD/144108/2019];
Author contributions
A.C.: conceptualization, methodology, formal analysis, validation, and
writing-original draft. A.H.: conceptualization, methodology, formalanalysis, and validation. F.T.R.: methodology, formal analysis, and validation. L.G.P.: methodology, formal analysis, and validation; E.V.: methodology and formal analysis. A.B.: methodology. T.G.S.: methodology. J.A.E.: conceptualization, formal analysis, validation, and writing the final manuscript. All authors read, amended, and approved the final version of the manuscript