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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Qin, Lianhua Wang, Jie Lu, Junmei Yang, Hua Zheng, Ruijuan Liu, Zhonghua Huang, Xiaochen Feng, Yonghong Hu, Zhongyi Ge, Baoxue |
| Abstract | Background The emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb), especially those that are multidrug resistant poses a serious threat to global tuberculosis control. However, the mechanism underlying the occurrence of drug resistance against more than one drug is poorly understood. Given that the Beijing/W strains are associated with outbreaks and multidrug resistance, they may harbor a genetic advantage and provide useful insight into the disease. One marker found in all Beijing/W Mtb strains is a deletion of RD105 region that results in a gene fusion, Rv0071/74, with a variable number (3–9 m) of VDP (V: Val, D: Asp; P: Pro) repeats (coded by gtggacccg repeat sequences) at the N-terminal. Here, we report that this variable number of VDP repeats in Rv0071/74 regulates the development of multidrug resistance. Results We collected and analyzed 1255 Beijing/W clinical strains. The results showed that the number of VDP repeats in Rv0071/74 was related to the development of multidrug resistance, and the deletion of Rv0071/74-9 m from Beijing/W clinical strain restored drug susceptibility. Rv0071/74-9 m also increased resistance to multiple drugs when transferred to different mycobacterial strains. Cell-free assays indicate that the domain carrying 4–9 VDP repeats (4–9 m) showed a variable binding affinity with peptidoglycan and Rv0071/74 cleaves peptidoglycan. Furthermore, Rv0071/74-9 m increased cell wall thickness and reduced the intracellular concentration of antibiotics. Conclusions These findings not only identify Rv0071/74 with VDP repeats as a newly identified multidrug resistance gene but also provide a new model for the development of multiple drug resistance. |
| Related Links | https://bmcbiol.biomedcentral.com/counter/pdf/10.1186/s12915-019-0628-6.pdf |
| Ending Page | 12 |
| Page Count | 12 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17417007 |
| DOI | 10.1186/s12915-019-0628-6 |
| Journal | BMC Biology |
| Issue Number | 1 |
| Volume Number | 17 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2019-01-25 |
| Access Restriction | Open |
| Subject Keyword | Life Sciences Mycobacterium tuberculosis RD105 region Rv0071/74-9 m fusion gene Multiple-drug resistance |
| Content Type | Text |
| Resource Type | Article |
| Subject | Ecology, Evolution, Behavior and Systematics Structural Biology Biochemistry, Genetics and Molecular Biology Plant Science Biotechnology Physiology Agricultural and Biological Sciences Cell Biology Developmental Biology |
| Journal Impact Factor | 4.4/2023 |
| 5-Year Journal Impact Factor | 5.4/2023 |
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