A5008737741- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Antibiotic Resistance in Bacteria
- Bacterial Genetics and Biotechnology
- DNA Repair Mechanisms
- Evolution and Genetic Dynamics
- Immune Response and Inflammation
- Genomics and Phylogenetic Studies
- Amino Acid Enzymes and Metabolism
- Metalloenzymes and iron-sulfur proteins
- Probiotics and Fermented Foods
- Escherichia coli research studies
- Computational Drug Discovery Methods
- interferon and immune responses
- Cancer Mechanisms and Therapy
- Galectins and Cancer Biology
- Microbial Natural Products and Biosynthesis
- RNA modifications and cancer
- Gut microbiota and health
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- Cancer Research and Treatments
- Glycosylation and Glycoproteins Research
- Wastewater Treatment and Nitrogen Removal
- Biochemical and Molecular Research
Shanghai Medical College of Fudan University
2021-2025
Fudan University
2016-2024
Shanghai Clinical Research Center
2022-2024
Shanghai Pulmonary Hospital
2022-2024
Shanghai Public Health Clinical Center
2014-2021
Chinese Academy of Medical Sciences & Peking Union Medical College
2021
Chinese University of Hong Kong
2013
Center for Excellence in Molecular Plant Sciences
2013
Shanghai Institutes for Biological Sciences
2013
Chinese Academy of Sciences
2013
Significance An improved understanding of fatty acid metabolism in pathogenic mycobacteria is critical for development new chemotherapeutics. Here, we identified FdmR, a previously uncharacterized transcriptional factor, as the key regulator catabolism pathogen Mycobacterium marinum . We demonstrated that FdmR optimizes utilization and allows high rate cell growth with modest consumption nutrients. Moreover, found suppresses degradation de novo-synthesized acids controls size abundance...
Growing evidence shows that generation of reactive oxygen species (ROS) derived from antibiotic-induced metabolic perturbation contribute to antibiotic lethality. However, our knowledge the mechanisms by which oxidative stress actually kills cells remains elusive. Here, we show oxidation dCTP underlies ROS-mediated lethality via induction DNA double-strand breaks (DSBs). Deletion mazG-encoded 5-OH-dCTP-specific pyrophosphohydrolase potentiates killing stationary-phase mycobacteria, but did...
Significance The global distribution of different Mtb lineages is very structured, with a few that are globally widespread, whereas many others restricted to particular geographic regions. Although local adaptation has been favored model for explaining the sympatric relationship between bacteria and host in these regions, this difficult study. Human migration led intermixing ethnicities disturbed bacterial population structure, thereby masking putative genetic determinants may have evolved...
Mycobacterial arabinogalactan (AG) is an essential cell wall component of mycobacteria and a frequent structural bio-synthetical target for anti-tuberculosis (TB) drug development. Here, we report that mycobacterial AG recognized by galectin-9 exacerbates infection. Administration AG-specific aptamers inhibits cellular infiltration caused Mycobacterium tuberculosis (Mtb) or bovis BCG, moderately increases survival Mtb-infected mice marinum-infected zebrafish. interacts with carbohydrate...
Generation of reactive oxygen species and nitrogen in phagocytes is an important innate immune response mechanism to eliminate microbial pathogens. It known that deoxynucleotides (dNTPs), the precursor nucleotides DNA synthesis, are one group significant targets for these oxidants incorporation oxidized dNTPs into genomic may cause mutations even cell death. Here we show mycobacterial dNTP pyrophosphohydrolase MazG safeguards bacilli genome by degrading 5-OH-dCTP, thereby, preventing it from...
Mycobacterial persistence mechanisms remain to be fully characterized. Screening a transposon insertion library of Mycobacterium marinum identified kdpA, whose inactivation reduced the fraction persisters after exposure rifampicin. kdpA encodes transmembrane protein that is part Kdp-ATPase, an ATP-dependent high-affinity potassium (K+) transport system. We found induced under low K+ conditions and required for pH homeostasis growth in media with concentrations K+. The Kdp system mutant...
Defence against oxidative stress is crucial for Mycobacterium tuberculosis to survive and replicate within macrophages. Mycobacteria have evolved multilayer antioxidant systems, including scavenging enzymes, iron homeostasis, repair pathways, metabolic adaptation, coping with stress. How these systems are coordinated enable the physiological adaptation different intensities of stress, however, remains unclear. To address this, we investigated expression kinetics well-characterized genes at...
The removal of mis-incorporated nucleotides by proofreading activity ensures DNA replication fidelity. Whereas the ε-exonuclease DnaQ is a well-established proofreader in model organism
Nitrate is one of the major inorganic nitrogen sources for microbes. Many bacterial and archaeal lineages have capacity to express assimilatory nitrate reductase (NAS), which catalyzes rate-limiting reduction nitrite. Although a pathway in mycobacteria has been proposed validated physiologically genetically, putative NAS enzyme yet be identified. Here, we report characterization novel encoded by Mycolicibacterium smegmatis Msmeg_4206, designated NasN, differs from canonical NASs its...
Many pathogens infect hosts through various immune evasion strategies. However, the molecular mechanisms by which pathogen proteins modulate and evade host response remain unclear. Enterohemorrhagic Escherichia coli (EHEC) is a pathological strain that can induce mitogen-activated protein (MAP) kinase (Erk, Jnk p38 MAPK) NF-κB pathway activation proinflammatory cytokine production, then causes diarrheal diseases such as hemorrhagic colitis hemolytic uremic syndrome. Transforming growth...
Lipids have been identified as important carbon sources for Mycobacterium tuberculosis (Mtb) to utilize in vivo. Thus gluconeogenesis bears a key role Mtb survive and replicate host. A rate-limiting enzyme of gluconeogenesis, fructose 1, 6-bisphosphatase (FBPase) is encoded by the gene glpX. The functions glpX were studied M. marinum, closely related species Mtb. deletion strain (ΔglpX) displayed altered attenuated virulence, bacterial proliferation. Metabolic profiles indicate an...
Network analysis of transcriptional signature typically relies on direct interaction between two highly expressed genes. However, this approach misses indirect and biological relevant interactions through a third factor (hub). Here we determine whether hub-based network can select an improved subset that correlates with change in stronger manner than the original signature. We have previously reported interferon-related (THP1r2 Mtb -induced) from Mycobacterium tuberculosis ( M. tb )-infected...
Rifamycins are a group of antibiotics with wide antibacterial spectrum. Although the binding target rifamycin has been well characterized, mechanisms underlying discrepant killing efficacy between gram-negative and gram-positive bacteria remain poorly understood. Using high-throughput screen combined targeted gene knockouts in model organism
Abstract Remove of mis-incorporated nucleotides ensures replicative fidelity. Although the ε-exonuclease DnaQ is a well-established proofreader in model organism Escherichia coli , proofreading mycobacteria relies on polymerase and histidinol phosphatase (PHP) domain despite presence an alternative homolog. Here, we show that depletion Mycolicibacterium smegmatis results increased mutation rate, leading to AT-biased mutagenesis elevated insertions/deletions homopolymer tract. We demonstrated...
The emergence of new Mycobacterium tuberculosis (Mtb) strains resistant to the key drugs currently used in clinic for treatment can substantially reduce probability therapy success, causing relevance and importance studies on development novel potent antibacterial agents targeting different vulnerable spots Mtb. In this study, 28,860 compounds from library bioactive molecules were screened identify potential inhibitors β-ketoacyl-acyl carrier protein synthase I (KasA), one enzymes involved...