Díaz-Mejía J Javier, Amábile-Cuevas Carlos F, Rosas Irma, Souza Valeria
Departamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Av. Universidad 2001, Col. Chamilpa, 62210 Cuernavaca, Morelos, Mexico.
Fundación Lusara, Apartado Postal 102-006, 08930, Mexico City, Mexico.
Microbiology (Reading). 2008 Jan;154(Pt 1):94-102. doi: 10.1099/mic.0.2007/008649-0.
Integrons are genetic elements that allow the mobilization and expression of smaller elements called gene cassettes, and are considered to be key elements in the evolution of antibiotic resistance among enteric bacteria. Although in nature integrons appear to be abundant, the presence of class 1 integrons in Escherichia coli has been reported to be much less frequent among isolates of non-human origin than among clinical ones. Searching for integrons in a wide variety of E. coli isolates we found a steep decline in class 1 integron prevalence when going from clinical strains to environmental ones, from outdoor urban dust to the microbiota of wild animals. Attempting to assess the causes of this decline, we addressed the evolution of integron integrases, comparing the amino acid sequence of various of these enzymes, the key proteins in gene-cassette mobilization. We found that all integrases are homologues, but different classes have been recruited by enteric bacteria, supporting the notion that integrons can frequently be gained and lost. Additionally, we found that phylogenetically distant organisms that bear intI1, such as E. coli and other enteric bacteria, but also the Gram-positive corynebacteria, have a similar preferential genomic codon usage (CU), suggesting that CU might play an important role in the acquisition and/or maintenance of integrons. In fact, the CU of intI1 is more similar to the preferential genomic CU of non-enteric bacteria than it is to that of E. coli. CU has been proposed to be involved in the retention of horizontally transferred genes; integrons in E. coli are often plasmid-borne. This might explain the reduced prevalence of integrons in enteric bacteria when not under the selective pressure of antibiotics. Collectively, our results provide evidence that class 1 integrons are important gene mobilizers within E. coli, but are not acquired and/or stably maintained without selective pressure. Thus, although not effective to reduce the prevalence of resistance itself, decreasing the use of antibiotics could be useful to diminish the presence of gene-mobilization machineries.
整合子是一种遗传元件，能够使被称为基因盒的较小元件进行移动并表达，被认为是肠道细菌抗生素耐药性进化中的关键元件。尽管在自然界中整合子似乎很常见，但据报道，在非人类来源的大肠杆菌分离株中，1类整合子的出现频率远低于临床分离株。在对各种大肠杆菌分离株进行整合子搜索时，我们发现从临床菌株到环境菌株，从城市户外灰尘到野生动物的微生物群，1类整合子的流行率急剧下降。为了评估这种下降的原因，我们研究了整合酶的进化，比较了这些酶（基因盒移动的关键蛋白）的各种氨基酸序列。我们发现所有整合酶都是同源物，但不同类别已被肠道细菌所利用，这支持了整合子可以频繁获得和丢失的观点。此外，我们发现携带intI1的系统发育距离较远的生物体，如大肠杆菌和其他肠道细菌，还有革兰氏阳性棒状杆菌，具有相似的优先基因组密码子使用情况（CU），这表明CU可能在整合子的获得和/或维持中起重要作用。事实上，intI1的CU与非肠道细菌的优先基因组CU比与大肠杆菌的更相似。有人提出CU参与水平转移基因的保留；大肠杆菌中的整合子通常是质粒携带的。这可能解释了在没有抗生素选择压力时肠道细菌中整合子流行率降低的原因。总的来说，我们的结果提供了证据，表明1类整合子是大肠杆菌内重要的基因移动元件，但在没有选择压力的情况下不会获得和/或稳定维持。因此，虽然减少抗生素的使用本身对降低耐药性流行率无效，但可能有助于减少基因移动机制的存在。
