ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
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2025
·Vol. 69
·期 5
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IF 4.5
Pusheng Xu,Yi Li,Bihan Xu,Dan Cao,Xu Dong,Yanghui Xiang,Xiuzhi Jiang,Xin Yuan,Yuwei Qiu,Ying Zhang
Mycobacterium abscessus is a fast-growing nontuberculous mycobacterium that can cause severe disease and poses a significant challenge for clinical management. New drugs are urgently needed for more effective treatment. Nitroxoline, an antibiotic used for treating urinary tract infections in Europe, has recently been shown to have promising activity against M. abscessus. However, the mechanism of its modified activity is not known. In anticipation for its potential clinical use, in this study, we investigated the mechanism of nitroxoline activity modification through mutant selection followed by whole-genome sequencing. We identified mutations in a transcriptional repressor MarR (MAB_2648c) controlling the expression of efflux pumps MmpS5-MmpL5 family that are associated with nitroxoline activity modification. Complementation of the mutants with the wild-type marR gene restored the MIC values to levels comparable to those of the wild-type strain. This study elucidates the key mechanism of how M. abscessus mutations modify the activity of nitroxoline, which has significant implications for rapid molecular detection of drug-resistant M. abscessus and for further studies on resistance mechanisms.
研究领域:
微生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Scientific Reports
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2017
·Vol. 7
·期 1
·1-9
·
IF 4.259
Wang Yulong,Wang Limin,Su Zhenhe,Xue Juanjuan,Dong Jinbo,Zhang Cunzheng,Hua Xiude,Wang Minghua,Liu Fengquan
We use the multiple antibiotic resistance regulator (MarR), as a highly selective biorecognition elements in a multipath colourimetric sensing strategy for the fast detection of Cu 2+ in water samples. The colourimetric assay is based on the aggregation of MarR-coated gold nanoparticles in the presence of Cu 2+ ions, which induces a red-to-purple colour change of the solution. The colour variation in the gold nanoparticle aggregation process can be used for qualitative and quantitative detection of Cu 2+ by the naked eye, and with UV–vis and smartphone-based approaches. The three analysis techniques used in the multipath colourimetric assay complement each other and provide greater flexibility for differing requirements and conditions, making the assay highly applicable for Cu 2+ detection. Under optimal conditions, the Cu 2+ concentration was quantified in less than 5 min with limits of detection for the naked eye, UV–vis and smartphone-based approaches of 1 μM, 405 nM and 61 nM, respectively. Moreover, the sensing system exhibited excellent selectivity and practical application for Cu 2+ detection in real water samples. Thus, our strategy has great potential for application in on-site monitoring of Cu 2+ , and the unique response of MarR towards copper ions may provide a new approach to Cu 2+ sensing.
研究领域:
分析化学
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环境科学
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纳米技术
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2017
·
IF 6.32
Yulong Wang,Zhenhe Su,Limin Wang,Jinbo Dong,Juanjuan Xue,Jiao Yu,Yuan Wang,Xiude Hua,Minghua Wang,Cunzheng Zhang,Fengquan Liu
We have developed a rapid and ultrasensitive surface-enhanced Raman scattering (SERS) assay for Cu2+ detection using the multiple antibiotic resistance regulator (MarR) as specific bridging molecules in a SERS hot-spot model. In the assay, Cu2+ induces formation of MarR tetramers, which provide Au nanoparticle (NP)–AuNP bridges, resulting in the formation of SERS hot spots. 4-Mercaptobenzoic acid (4-MBA) was used as a Raman reporter. The addition of Cu2+ increased the Raman intensity of 4-MBA. Use of a dual hot-spot signal-amplification strategy based on AuNP–AgNP heterodimers combined through antigen–antibody reactions increased the sensitivity of the sensing platform by 50-fold. The proposed method gave a linear response for Cu2+ detection in the range of 0.5–1000 nM, with a detection limit of 0.18 nM, which is 5 orders of magnitude lower than the U.S. Environmental Protection Agency limit for Cu2+ in drinking water (20 μM). In addition, all analyses can be completed in less than 15 min. The high sensitivity, high specificity, and rapid detection capacity of the SERS assay therefore provide a combined advantage over current assays.
研究领域:
分析化学
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纳米技术
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环境科学
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DOI
PubMed
高影响因子
Frontiers in Microbiology
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2026
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IF 5.8
Abulimiti Abudukadier,Qiao Zhang,Gang Li,Haiqi Chen,Peibo Li,Zhen Gong,Jianping Xie
The MarR family of transcription factors in Mycobacterium tuberculosis plays a critical role in bacterial adaptation to host stresses, yet the function of many members remains unknown. Here, we characterize the novel MarR regulator Rv0737 and its homolog Ms_1492 in M. smegmatis . Overexpression of Rv0737 severely impaired bacterial growth, cell division, and biofilm formation, while increasing susceptibility to oxidative stress and the cell wall-targeting drug isoniazid. Conversely, deletion of ms_1492 altered cell envelope permeability and lipid composition, enhanced ATP synthesis, and conferred mild tolerance to H 2 O 2 and isoniazid. Lipid profiling and transcriptomic analysis revealed significant dysregulation of lipid metabolism genes. Crucially, electrophoretic mobility shift assays demonstrated that both Rv0737 and Ms_1492 directly bind to the promoter region of the sigL-rslA operon, which encodes an alternative sigma factor and its anti-sigma factor. Our findings establish a direct regulatory pathway wherein Rv0737/Ms_1492 modulates bacterial growth, cell envelope integrity, and stress response by targeting the sigL-rslA operon, identifying this system as a potential therapeutic target for combating drug-resistant tuberculosis.
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高影响因子
Synthetic and Systems Biotechnology
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2020
·
IF 0
Ruida Wang,Fanjing Kong,Haizhen Wu,Bingbing Hou,Yajing Kang,Yuan Cao,Shiwei Duan,Jiang Ye,Huizhan Zhang
The lincosamide family antibiotic lincomycin is a widely used antibacterial pharmaceutical generated by Streptomyces lincolnensis , and the high-yield strain B48 produces 2.5 g/L lincomycin, approximately 30-fold as the wild-type strain NRRL 2936. Here, the genome of S. lincolnensis B48 was completely sequenced, revealing a ~10.0 Mb single chromosome with 71.03% G + C content. Based on the genomic information, lincomycin-related primary metabolism network was constructed and the secondary metabolic potential was analyzed. In order to dissect the overproduction mechanism, a comparative genomic analysis with NRRL 2936 was performed. Three large deletions (LDI-III), one large inverted duplication (LID), one long inversion and 80 small variations (including 50 single nucleotide variations, 13 insertions and 17 deletions) were found in B48 genome. Then several crucial mutants contributing to higher production phenotype were validated. Deleting of a MarR-type regulator-encoding gene slinc377 from LDI, and the whole 24.7 kb LDII in NRRL 2936 enhanced lincomycin titer by 244% and 284%, respectively. Besides, lincomycin production of NRRL 2936 was increased to 7.7-fold when a 71 kb supercluster BGC33 from LDIII was eliminated. As for the duplication region, overexpression of the cluster situated genes lmbB2 and lmbU , as well as two novel transcriptional regulator-encoding genes ( slinc191 and slinc348 ) elevated lincomycin titer by 77%, 75%, 114% and 702%, respectively. Furthermore, three negative correlation genes ( slinc6156 , slinc4481 and slinc6011 ) on lincomycin biosynthesis, participating in regulation were found out. And surprisingly, inactivation of RNase J-encoding gene slinc6156 and TPR (tetratricopeptide repeat) domain-containing protein-encoding gene slinc4481 achieved lincomycin titer equivalent to 83% and 68% of B48, respectively, to 22.4 and 18.4-fold compared to NRRL 2936. Therefore, the comparative genomics approach combined with confirmatory experiments identified that large fragment deletion, long sequence duplication, along with several mutations of genes, especially regulator genes, are crucial for lincomycin overproduction.
研究领域:
微生物学
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基因组学
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药学
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分子生物学
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DOI
PubMed
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