In vivo evolution of drug-resistant Mycobacterium tuberculosis in patients during long-term treatment
Abstract Background In the current scenario, the drug-resistant tuberculosis is a significant challenge in the control of tuberculosis worldwide. In order to investigate the in vivo evolution of drug-resistant M. tuberculosis, the present study envisaged sequencing of the draft genomes of 18 serial...
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| Format: | Article |
| Language: | English |
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BMC
2018-08-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-018-5010-5 |
| _version_ | 1818197261915521024 |
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| author | Yuhui Xu Fei Liu Suting Chen Jiannan Wu Yongfei Hu Baoli Zhu Zhaogang Sun |
| author_facet | Yuhui Xu Fei Liu Suting Chen Jiannan Wu Yongfei Hu Baoli Zhu Zhaogang Sun |
| author_sort | Yuhui Xu |
| collection | DOAJ |
| description | Abstract Background In the current scenario, the drug-resistant tuberculosis is a significant challenge in the control of tuberculosis worldwide. In order to investigate the in vivo evolution of drug-resistant M. tuberculosis, the present study envisaged sequencing of the draft genomes of 18 serial isolates from four pre-extensively drug-resistant (pre-XDR) tuberculosis patients for continuous genetic alterations. Results All of the isolates harbored single nucleotide polymorphisms (SNPs) ranging from 1303 to 1309 with M. tuberculosis H37Rv as the reference. SNPs ranged from 0 to 12 within patients. The evolution rates were higher than the reported SNPs of 0.5 in the four patients. All the isolates exhibited mutations at sites of known drug targets, while some contained mutations in uncertain drug targets including folC, proZ, and pyrG. The compensatory substitutions for rescuing these deleterious mutations during evolution were only found in RpoC I491T in one patient. Many loci with microheterogeneity showed transient mutations in different isolates. Ninety three SNPs exhibited significant association with refractory pre-XDR TB isolates. Conclusions Our results showed evolutionary changes in the serial genetic characteristics of the pre-XDR TB patients due to accumulation of the fixed drug-resistant related mutations, and the transient mutations under continuous antibiotics pressure over several years. |
| first_indexed | 2024-12-12T01:47:10Z |
| format | Article |
| id | doaj.art-e5a456f5670d4f10b53db4f82f48bfa8 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-12T01:47:10Z |
| publishDate | 2018-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-e5a456f5670d4f10b53db4f82f48bfa82022-12-22T00:42:33ZengBMCBMC Genomics1471-21642018-08-0119111110.1186/s12864-018-5010-5In vivo evolution of drug-resistant Mycobacterium tuberculosis in patients during long-term treatmentYuhui Xu0Fei Liu1Suting Chen2Jiannan Wu3Yongfei Hu4Baoli Zhu5Zhaogang Sun6Institute of Chinese Materia medica, China Academy of Chinese Medical ScienceCAS key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of ScienceNational Tuberculosis Clinical Laboratory, Beijing Chest Hospital, Capital Medical UniversityNational Tuberculosis Clinical Laboratory, Beijing Chest Hospital, Capital Medical UniversityCAS key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of ScienceCAS key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of ScienceNational Tuberculosis Clinical Laboratory, Beijing Chest Hospital, Capital Medical UniversityAbstract Background In the current scenario, the drug-resistant tuberculosis is a significant challenge in the control of tuberculosis worldwide. In order to investigate the in vivo evolution of drug-resistant M. tuberculosis, the present study envisaged sequencing of the draft genomes of 18 serial isolates from four pre-extensively drug-resistant (pre-XDR) tuberculosis patients for continuous genetic alterations. Results All of the isolates harbored single nucleotide polymorphisms (SNPs) ranging from 1303 to 1309 with M. tuberculosis H37Rv as the reference. SNPs ranged from 0 to 12 within patients. The evolution rates were higher than the reported SNPs of 0.5 in the four patients. All the isolates exhibited mutations at sites of known drug targets, while some contained mutations in uncertain drug targets including folC, proZ, and pyrG. The compensatory substitutions for rescuing these deleterious mutations during evolution were only found in RpoC I491T in one patient. Many loci with microheterogeneity showed transient mutations in different isolates. Ninety three SNPs exhibited significant association with refractory pre-XDR TB isolates. Conclusions Our results showed evolutionary changes in the serial genetic characteristics of the pre-XDR TB patients due to accumulation of the fixed drug-resistant related mutations, and the transient mutations under continuous antibiotics pressure over several years.http://link.springer.com/article/10.1186/s12864-018-5010-5Drug-resistant tuberculosisTreatmentGenetic changesSNP |
| spellingShingle | Yuhui Xu Fei Liu Suting Chen Jiannan Wu Yongfei Hu Baoli Zhu Zhaogang Sun In vivo evolution of drug-resistant Mycobacterium tuberculosis in patients during long-term treatment BMC Genomics Drug-resistant tuberculosis Treatment Genetic changes SNP |
| title | In vivo evolution of drug-resistant Mycobacterium tuberculosis in patients during long-term treatment |
| title_full | In vivo evolution of drug-resistant Mycobacterium tuberculosis in patients during long-term treatment |
| title_fullStr | In vivo evolution of drug-resistant Mycobacterium tuberculosis in patients during long-term treatment |
| title_full_unstemmed | In vivo evolution of drug-resistant Mycobacterium tuberculosis in patients during long-term treatment |
| title_short | In vivo evolution of drug-resistant Mycobacterium tuberculosis in patients during long-term treatment |
| title_sort | in vivo evolution of drug resistant mycobacterium tuberculosis in patients during long term treatment |
| topic | Drug-resistant tuberculosis Treatment Genetic changes SNP |
| url | http://link.springer.com/article/10.1186/s12864-018-5010-5 |
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