ArticleBMC biology2019
A deletion in the RD105 region confers resistance to multiple drugs in Mycobacterium tuberculosis.
Article in BMC biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 28 citations in OpenAlex.
- Cross-continental transmission and host adaptation ofiMetaOmics · 2025Article
- In Vitro Antimicrobial Activity of Contezolid AgainstMicroorganisms · 2025Article
- TheeLife · 2025Article
- Interred mechanisms of resistance and host immune evasion revealed through network-connectivity analysis ofmSystems · 2025Article
- Universal Lineage-Independent Markers of Multidrug Resistance inMicroorganisms · 2024Article
- Azetidines Kill Multidrug-ResistantJournal of medicinal chemistry · 2024Article
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- Omics analysis of Mycobacterium tuberculosis isolates uncovers Rv3094c, an ethionamide metabolism-associated gene.Communications biology · 2023Article
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- Identification of gene fusion events inNAR genomics and bioinformatics · 2020Article
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- Hypoxic Non-replicating PersistentFrontiers in microbiology · 2019Article
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10 authors at 1 institution in 1 country.
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Abstract
backgroundThe 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.
resultsWe 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.
conclusionsThese 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.
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