Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 7, 8092 Zurich, Switzerland.
J Antimicrob Chemother. 2013 May;68(5):986-91. doi: 10.1093/jac/dks531. Epub 2013 Jan 22.
To characterize Tn6198, a novel conjugative transposon from the clinical Listeria monocytogenes strain TTH-2007, which contains the tetracycline and trimethoprim resistance genes tet(M) and dfrG, respectively, and to assess its transferability in vitro and in situ.
The complete sequence of Tn6198 was determined using a primer walking strategy. Horizontal gene transfer studies were performed by filter matings, as well as on the surface of smear-ripened cheese and smoked salmon. The presence of Tn916-like circular intermediates was determined by PCR. Antibiotic resistance was determined by the broth microdilution method and microarray hybridization.
Sequencing of Tn6198 revealed that a 3.3 kb fragment containing dfrG was integrated between open reading frames 23 and 24 of Tn916. Furthermore, an additional copy of Tn916 was present in L. monocytogenes TTH-2007. Both elements were transferred simultaneously and separately in vitro to recipients L. monocytogenes 10403S and Enterococcus faecalis JH2-2 by conjugation, resulting in either tetracycline- and trimethoprim-resistant or solely tetracycline-resistant transconjugants. On the surface of cheese and salmon, only L. monocytogenes 10403S transconjugants were detected.
This study reports the first Tn916-like element associated with a trimethoprim resistance gene, as well as the first fully characterized transposon conferring multidrug resistance in L. monocytogenes. This is of concern, as trimethoprim is administered to listeriosis patients with β-lactam allergy and as Tn6198 has a large potential for dissemination, indicated by both intra-species and inter-genus transfer.
对来自临床李斯特菌菌株 TTH-2007 的新型可接合转座子 Tn6198 进行特征描述,该转座子包含四环素和甲氧苄啶耐药基因 tet(M)和 dfrG。评估其在体外和体内的可转移性。
使用引物步行策略确定 Tn6198 的完整序列。通过滤膜交配以及在涂抹成熟奶酪和熏三文鱼表面进行水平基因转移研究。通过 PCR 确定是否存在 Tn916 样环状中间体。通过肉汤微量稀释法和微阵列杂交确定抗生素耐药性。
测序 Tn6198 表明,一个包含 dfrG 的 3.3 kb 片段整合在 Tn916 的开放阅读框 23 和 24 之间。此外,李斯特菌 TTH-2007 中还存在另一个 Tn916 拷贝。这两个元件通过接合在体外同时且分别转移到李斯特菌 10403S 和粪肠球菌 JH2-2 的受体中,导致四环素和甲氧苄啶耐药或仅四环素耐药的转导子。在奶酪和三文鱼表面,仅检测到李斯特菌 10403S 转导子。
本研究报告了第一个与甲氧苄啶耐药基因相关的 Tn916 样元件,以及第一个在李斯特菌中完全表征的赋予多药耐药性的转座子。这令人担忧,因为甲氧苄啶用于对β-内酰胺类抗生素过敏的李斯特菌病患者,并且 Tn6198 具有广泛的传播潜力,这表明在种内和种间都可以转移。