Nature Communications · 2024 · 11 citations · 51 references
Life SciencesGeneticsMicrobiologyGene ExpressionGenomicsMicrobial GeneticsAntibiotic ResistanceAntibiotic Resistance GeneticsHorizontal Gene TransferResistance GenesResistance In Gram-negative BacteriaTranslation In ProkaryotesAntibiotic Resistance GenesBacterial Multidrug ResistanceGene Cassette ArraysIntegron-mediated Gene TransferMultidrug-resistant Gram-negative BacteriaResistance Gene CassettesResistance Gene DisseminationResistance Gene Expression Regulation
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. Authors explore an integron model to show that expression of a cassette is strongly determined by the identity of the cassette that precedes it.
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