Strict relationship between class 1 integrons and resistance to sulfamethoxazole in Escherichia coli
Strict relationship between class 1 integrons and resistance to sulfamethoxazole in Escherichia coli
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DOI：
10.1016/j.micpath.2021.105206
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发表时间：
2021-10-06
影响因子：
3.8
通讯作者：
Poey, Maria Eloisa
中科院分区：
文献类型：
--
作者：
de los Santos, Eliana;Lavina, Magela;Poey, Maria Eloisa
抗生素耐药性是一个健康问题。1类整合子(Int1)是导致这一问题的遗传因素，因为它们在可变区携带不同的抗生素耐药基因，经常是dfrA(对甲氧苄氨嘧啶耐药)，在其保守区携带sul1基因(对磺胺类药物，如磺胺类药物，如磺胺类)耐药)。这些是合成的抗生素，通过阻断叶酸合成途径中的两种酶起作用。在临床上，甲氧苄氨嘧啶(TMP)和磺胺甲恶唑(SMX)联合使用，称为复方新诺明(SXT)。本研究收集了230株致尿路感染的大肠埃希菌，目的有三：1)分析其对抗叶酸抗生素的敏感性表型；2)确定其对SMX耐药的遗传基础；3)将表型和基因分型数据与Int1的存在相关联。对SMX、TMP和SXT的耐药率分别为54%、45%和41%。对与磺胺类药物耐药有关的移动基因sul1、sul2和sul3进行了聚合酶链式反应检测：除3株外，所有的磺胺类耐药菌株都至少含有其中一种基因。对于后者，可以排除成为目标FolP突变体的可能性，这表明在大肠杆菌中存在一种尚不清楚的对SMX的抗性机制。之前被归类为Int1阳性的所有50株菌株(因为它们具有整合酶的intI1基因)都对SMX产生了抗药性：大多数菌株只有sul1，或者与sul2或sul3一起携带，其他只有sul2，还有一株缺乏所有的sul基因。此外，16株sul1(+)intI1(-)菌株还含有其他典型的整合子序列。也就是说，在任何情况下，Sul1基因的检测都不是独立于其他Int1序列的。因此，我们认为，对于Int1和intI1基因的存在，sul1基因都是一个很好的标记。根据这一标准，我们收集的Int1的患病率从22%(50个intI1(+))增加到29%(66个intI1(+)和/或sul1(+))。在这66株Int1(+)菌株中，63株对TMP耐药。这项工作的主要结论是，1类整合子的存在总是需要磺胺甲恶唑耐药的细胞环境。总而言之，这些整合子似乎与抗叶酸类化合物的耐药性密切相关。
Antibiotic resistance is a health concern. Class 1 integrons (Int1) are genetic elements that contribute to the problem, as they carry different antibiotic resistance genes in their variable region, frequently dfrA (resistance to trimethoprim) and, in their conserved region, the sul1 gene (resistance to sulfonamides, e.g. sulfamethoxazole). These are synthetic antibiotics that work by blocking two enzymes in the folic acid synthesis pathway. In the clinic, the combination of trimethoprim (TMP) and sulfamethoxazole (SMX), called co-trimoxazole (SXT), is widely used. A collection of 230 uropathogenic Escherichia coli strains was studied with three objectives: i) to analyze their phenotype of susceptibility to antifolate antibiotics, ii) to determine the genetic basis of their resistance to SMX, and iii) to correlate the phenotypic and genotypic data with the presence of Int1. The prevalence of resistance to SMX, TMP, and SXT was 54%, 45%, and 41%, respectively. The mobile genes sul1, sul2 and sul3, which confer resistance to sulfonamides, were PCR-surveyed: all sulfa-resistant strains were found to contain at least one of these genes, with the exception of three strains. For these latter, the possibility of being target folP mutants could be ruled out, pointing to the existence of a still unknown mechanism of resistance to SMX in E. coli. All 50 strains previously cataloged as positive for Int1 (because they had an intI1 gene for the integrase) were resistant to SMX: most had sul1, alone or with sul2 or sul3, others only had sul2, and one lacked every sul gene. In addition, 16 sul1(+) intI1(-) strains were found to contain other typical integron sequences. That is, in no case was the sul1 gene detected independently of other Int1 sequences. Therefore, we propose that the sul1 gene would be a good marker for the presence of Int1, as well as the intI1 gene. Following this criterion, the prevalence of Int1 in our collection increased from 22% (50 intI1(+)) to 29% (66 intI1(+) and/or sul1(+)). Of these 66 Int1(+) strains, 63 were resistant to TMP. The main conclusion in this work is that the presence of a class 1 integron would always require a sulfamethoxazole resistant cellular context. In more general terms, these integrons appear to be closely related to resistance to antifolate compounds.