The expression of integron arrays is shaped by the translation rate of cassettes

André Carvalho (), Alberto Hipólito, Filipa Trigo da Roza, Lucía García-Pastor, Ester Vergara, Aranzazu Buendía, Teresa García-Seco and José Antonio Escudero ()
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André Carvalho: Molecular Basis of Adaptation. Departamento de Sanidad Animal. Universidad Complutense de Madrid
Alberto Hipólito: Molecular Basis of Adaptation. Departamento de Sanidad Animal. Universidad Complutense de Madrid
Filipa Trigo da Roza: Molecular Basis of Adaptation. Departamento de Sanidad Animal. Universidad Complutense de Madrid
Lucía García-Pastor: Molecular Basis of Adaptation. Departamento de Sanidad Animal. Universidad Complutense de Madrid
Ester Vergara: Molecular Basis of Adaptation. Departamento de Sanidad Animal. Universidad Complutense de Madrid
Aranzazu Buendía: Universidad Complutense de Madrid
Teresa García-Seco: Universidad Complutense de Madrid
José Antonio Escudero: Molecular Basis of Adaptation. Departamento de Sanidad Animal. Universidad Complutense de Madrid

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53525-6

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