Complete genome sequencing of transposon-mediated sulfamethoxazole resistance encoded by the Sul1 gene in multidrug-resistant Nocardia farcinica SZ 1509
ABSTRACT: Objectives: The objective of this study is to explore the molecular basis of trimethoprim-sulfamethoxazole (SXT) resistance in Nocardia, an SXT-resistant N. farcinica strain, named SZ 1509, by whole-genome sequencing. Methods: Antimicrobial susceptibility testing of SZ 1509 was performed...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Journal of Global Antimicrobial Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221371652200056X |
| _version_ | 1811210573139935232 |
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| author | Yanlin Che Shuai Xu Yutong Kang Xueping Liu Yuan Yue Lichao Han Xiaotong Qiu Dan Li Yongliang Lou Zhenjun Li |
| author_facet | Yanlin Che Shuai Xu Yutong Kang Xueping Liu Yuan Yue Lichao Han Xiaotong Qiu Dan Li Yongliang Lou Zhenjun Li |
| author_sort | Yanlin Che |
| collection | DOAJ |
| description | ABSTRACT: Objectives: The objective of this study is to explore the molecular basis of trimethoprim-sulfamethoxazole (SXT) resistance in Nocardia, an SXT-resistant N. farcinica strain, named SZ 1509, by whole-genome sequencing. Methods: Antimicrobial susceptibility testing of SZ 1509 was performed by broth microdilution, Etest, and disk diffusion arrays. Genome sequencing and analysis were performed to discover the SXT resistance determinant and its genetic context. Inverse PCR was conducted to confirm the circular form of the composite transposon. PCR for the sul1 gene was performed among SXT-susceptible isolates. Results: SZ 1509 is resistant to many drugs, especially SXT, with a minimum inhibitory concentration (MIC) of up to 32/608 µg/mL (ratio of 1:19 for trimethoprim: sulfamethoxazole). Its assembled genome consists of one chromosome and four plasmids with a total size of 6 613 629 bp and 71.1% of GC content. The plasmid 2 was found to carry one IS6-composite transposon containing IS6100 carrying the sul1 gene, one tellurite resistance gene TerC, and several transcriptional regulators. Inverse PCR analyses showed its circular form. All 10 SXT-susceptible isolates do not contain sul1. In addition, mutations with strong associations to SXT resistance were not conclusive. Conclusion: This is the first study to elucidate the transposon-mediated sulfamethoxazole resistance in N. farcinica. Our results provide insights on acquired drug resistance of N. farcinica and further suggest that the prevalence and correlation of this resistance's determinants in clinical isolates should be continuously monitored to provide effective clinical management of its resultant diseases. |
| first_indexed | 2024-04-12T04:58:17Z |
| format | Article |
| id | doaj.art-8a5ac89832144c5497f169a45ab2d109 |
| institution | Directory Open Access Journal |
| issn | 2213-7165 |
| language | English |
| last_indexed | 2024-04-12T04:58:17Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj.art-8a5ac89832144c5497f169a45ab2d1092022-12-22T03:47:04ZengElsevierJournal of Global Antimicrobial Resistance2213-71652022-09-01306065Complete genome sequencing of transposon-mediated sulfamethoxazole resistance encoded by the Sul1 gene in multidrug-resistant Nocardia farcinica SZ 1509Yanlin Che0Shuai Xu1Yutong Kang2Xueping Liu3Yuan Yue4Lichao Han5Xiaotong Qiu6Dan Li7Yongliang Lou8Zhenjun Li9Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaWenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China, Ningxia University, Ningixia, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaWenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; Corresponding authors: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.ABSTRACT: Objectives: The objective of this study is to explore the molecular basis of trimethoprim-sulfamethoxazole (SXT) resistance in Nocardia, an SXT-resistant N. farcinica strain, named SZ 1509, by whole-genome sequencing. Methods: Antimicrobial susceptibility testing of SZ 1509 was performed by broth microdilution, Etest, and disk diffusion arrays. Genome sequencing and analysis were performed to discover the SXT resistance determinant and its genetic context. Inverse PCR was conducted to confirm the circular form of the composite transposon. PCR for the sul1 gene was performed among SXT-susceptible isolates. Results: SZ 1509 is resistant to many drugs, especially SXT, with a minimum inhibitory concentration (MIC) of up to 32/608 µg/mL (ratio of 1:19 for trimethoprim: sulfamethoxazole). Its assembled genome consists of one chromosome and four plasmids with a total size of 6 613 629 bp and 71.1% of GC content. The plasmid 2 was found to carry one IS6-composite transposon containing IS6100 carrying the sul1 gene, one tellurite resistance gene TerC, and several transcriptional regulators. Inverse PCR analyses showed its circular form. All 10 SXT-susceptible isolates do not contain sul1. In addition, mutations with strong associations to SXT resistance were not conclusive. Conclusion: This is the first study to elucidate the transposon-mediated sulfamethoxazole resistance in N. farcinica. Our results provide insights on acquired drug resistance of N. farcinica and further suggest that the prevalence and correlation of this resistance's determinants in clinical isolates should be continuously monitored to provide effective clinical management of its resultant diseases.http://www.sciencedirect.com/science/article/pii/S221371652200056XNocardia farcinicaTrimethoprim-sulfamethoxazoleAcquired resistancesul1Composite transposonComplete genome sequencing |
| spellingShingle | Yanlin Che Shuai Xu Yutong Kang Xueping Liu Yuan Yue Lichao Han Xiaotong Qiu Dan Li Yongliang Lou Zhenjun Li Complete genome sequencing of transposon-mediated sulfamethoxazole resistance encoded by the Sul1 gene in multidrug-resistant Nocardia farcinica SZ 1509 Journal of Global Antimicrobial Resistance Nocardia farcinica Trimethoprim-sulfamethoxazole Acquired resistance sul1 Composite transposon Complete genome sequencing |
| title | Complete genome sequencing of transposon-mediated sulfamethoxazole resistance encoded by the Sul1 gene in multidrug-resistant Nocardia farcinica SZ 1509 |
| title_full | Complete genome sequencing of transposon-mediated sulfamethoxazole resistance encoded by the Sul1 gene in multidrug-resistant Nocardia farcinica SZ 1509 |
| title_fullStr | Complete genome sequencing of transposon-mediated sulfamethoxazole resistance encoded by the Sul1 gene in multidrug-resistant Nocardia farcinica SZ 1509 |
| title_full_unstemmed | Complete genome sequencing of transposon-mediated sulfamethoxazole resistance encoded by the Sul1 gene in multidrug-resistant Nocardia farcinica SZ 1509 |
| title_short | Complete genome sequencing of transposon-mediated sulfamethoxazole resistance encoded by the Sul1 gene in multidrug-resistant Nocardia farcinica SZ 1509 |
| title_sort | complete genome sequencing of transposon mediated sulfamethoxazole resistance encoded by the sul1 gene in multidrug resistant nocardia farcinica sz 1509 |
| topic | Nocardia farcinica Trimethoprim-sulfamethoxazole Acquired resistance sul1 Composite transposon Complete genome sequencing |
| url | http://www.sciencedirect.com/science/article/pii/S221371652200056X |
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