Molecular Basis of Adaptation. Departamento de Sanidad Animal. Universidad Complutense de Madrid, Madrid, Spain.
VISAVET Health Surveillance Centre, Universidad Complutense de Madrid, Madrid, Spain.
Nat Commun. 2024 Oct 25;15(1):9232. doi: 10.1038/s41467-024-53525-6.
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 P 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 P.
整合子是革兰氏阴性菌中多药耐药性兴起和传播的关键因素。这些遗传平台捕获含有无启动子基因的盒,并将其储存在可变长度的阵列中。在当前的整合子模型中,盒的表达由平台中的 P 启动子赋予,并假定其表达随距离的增加而降低。在这里,我们使用包含 136 个抗生素耐药盒的大型集合来探索这个模型,并表明距离的影响实际上可以忽略不计。相反,盒对下游基因的表达有很大的影响,因为它们的翻译率影响整个多顺反子 mRNA 分子的稳定性。因此,翻译率降低的盒会降低下游盒的表达和耐药表型。我们的数据提出了一个整合子模型,其中表达取决于上游盒的翻译,而不是与 P 的距离。