A5056394760- Pneumonia and Respiratory Infections
- Bacterial Infections and Vaccines
- Antibiotic Resistance in Bacteria
- Acute Myeloid Leukemia Research
- Streptococcal Infections and Treatments
- Bacteriophages and microbial interactions
- Retinoids in leukemia and cellular processes
- Antimicrobial Resistance in Staphylococcus
- Cancer therapeutics and mechanisms
- Influenza Virus Research Studies
- Bacterial biofilms and quorum sensing
- Pharmacological Effects of Natural Compounds
- Bacterial Genetics and Biotechnology
- Bacillus and Francisella bacterial research
- RNA and protein synthesis mechanisms
- Probiotics and Fermented Foods
- Biopolymer Synthesis and Applications
- Vector-borne infectious diseases
- Bacterial Identification and Susceptibility Testing
- Vector-Borne Animal Diseases
- Escherichia coli research studies
- Traditional Chinese Medicine Studies
- Respiratory viral infections research
- Pneumocystis jirovecii pneumonia detection and treatment
- Chronic Myeloid Leukemia Treatments
Tsinghua University
2014-2025
Center for Life Sciences
2020-2025
First Affiliated Hospital of Soochow University
2020-2024
Danaher (China)
2024
Soochow University
2020-2024
National Clinical Research
2023-2024
Lanzhou Petrochemical Polytechnic
2024
State Key Laboratory of Biotherapy
2014
Sichuan University
2014
Jilin University
2010-2011
Staphylococcus aureus, a Gram-positive bacterium causes number of devastating human diseases, such as infective endocarditis, osteomyelitis, septic arthritis and sepsis. S. aureus SraP, surface-exposed serine-rich repeat glycoprotein (SRRP), is required for the pathogenesis endocarditis via its ligand-binding region (BR) adhering to platelets. It remains unclear how SraP interacts with host. Here we report 2.05 Å crystal structure BR revealing an extended rod-like architecture four discrete...
Hypermucoviscosity is a hallmark of hypervirulent Klebsiella pneumoniae (hvKP). However, the molecular basis its regulation largely unknown. We hypothesize that hypermucoviscosity modulated via two-component signal transduction systems (TCSs). In-frame deletion mutants all 33 response regulators hvKP ATCC43816 were generated using CRISPR/CAS and evaluated for their impacts on hypermucoviscosity. The regulator OmpR required
Streptococcus pneumoniae, a human pathogen, is naturally capable of colonizing the upper airway and sometimes disseminating to remote tissue sites. Previous studies have shown that S. pneumoniae able evade complement-mediated innate immunity by recruiting complement factor H (FH), alternative pathway inhibitor. Pneumococcal binding FH has been attributed choline-binding protein A (CbpA) its allelic variants, all which are surface-exposed proteins. In this study, we sought determine molecular...
Pneumococcal disease is caused by Streptococcus pneumoniae , including pneumonia, meningitis and sepsis. Capsular polysaccharides (CPSs) have been shown as effective antigens to stimulate protective immunity against pneumococcal disease. A major step in the production of vaccines prepare CPSs that meet strict quality standards immunogenicity safety. The impurities come from bacterial proteins, nucleic acids cell wall polysaccharides. Traditionally, impurity level refined reduced optimization...
Yersinia pestis, the etiological agent of devastating plague, has caused three pandemics in human history. While known for its fatality, it long been intriguing that biovar microtus strains are highly attenuated to humans. The survival and replication within macrophages critical early stages Y. pestis lifestyle warm-blooded hosts. Here, we demonstrate a frameshift truncation gppA, gene encoding phosphohydrolase GppA responsible conversion stringent response alarmone pppGpp ppGpp,...
Abstract Streptococcus pneumoniae naturally colonizes the nasopharynx as a commensal organism and sometimes causes infections in remote tissue sites. This bacterium is highly capable of resisting host innate immunity during nasopharyngeal colonization disseminating infections. The ability to recruit complement factor H (FH) by S. has been implicated bacterial immune evasion mechanism against complement-mediated clearance because FH alternative pathway inhibitor. recruits through previously...
Background The scavenging ability of sufficient divalent metal ions is pivotal for pathogenic bacteria to survive in the host. ATP-binding cassette (ABC)-type transporters provide a considerable amount different transition metals bacterial growth. TroA substrate binding protein uptake multiple ions. However, function and structure homologue from epidemic Streptococcus suis isolates (SsTroA) have not been characterized. Methodology/Principal Findings Here we determined crystal SsTroA highly...
Background Ear infection or otitis media (OM) accounts for most bacterial respiratory infections in children both developed and developing nations. Streptococcus pneumoniae, nontypeable Haemophilus influenzae, Moraxella catarrhalis are the major OM pathogens. However, little is known about genetic basis of largely due to practical difficulties conducting research ear models genetically manipulating clinical isolates. Here, we report first genome-scale vivo screen genes required a chinchilla...
Vaccination has significantly reduced the incidence of invasive infections caused by several bacterial pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. However, no vaccines are available for many other pathogens. A major hurdle in vaccine development is lack functional markers to quantify immunity eliminating pathogens during process infection. Based on our recent discovery liver as organ vaccine-induced clearance blood-borne virulent...
A series of novel teraryl oxazolidinone compounds was designed, synthesized, and evaluated for their antimicrobial activity toxicities. The with aromatic N-heterocyclic substituents at the 4-position pyrazolyl ring showed better antibacterial against tested bacteria than other different patterns substitution. Among all potent compounds, 10f exhibited promising safety profile in MTT assays hERG K+ channel inhibition test. Furthermore, its phosphate found to be highly soluble water (47.1...
In an isogenic cell population, phenotypic heterogeneity among individual cells is common and critical for survival of the population under different environment conditions. DNA modification important epigenetic factor that can regulate heterogeneity. The single molecule real-time (SMRT) sequencing technology provides a unique platform detecting wide range modifications, including N6-methyladenine (6-mA), N4-methylcytosine (4-mC) 5-methylcytosine (5-mC). Here we present qDNAmod, novel...
Optochin, a cinchona alkaloid derivative discovered over 100 years ago, possesses highly selective antibacterial activity toward Streptococcus pneumoniae. Pneumococcal disease remains the leading source of bacterial pneumonia and meningitis worldwide. The structure–activity relationships optochin were examined through modification to both quinoline quinuclidine subunits, which led identification analogue 48 with substantially improved activity. Resistance molecular modeling studies indicate...
undergoes phase variation or spontaneous, reversible phenotypic in colony opacity, encapsulation, and pilus expression. The opacity appears to occur all strains, whereas the switches production of capsule have been observed several strains. This chapter elaborates on since this phenomenon has extensively characterized.
Abstract Type I restriction-modification (R-M) systems consist of a DNA endonuclease (HsdR, HsdM and HsdS subunits) methyltransferase (HsdM subunits). The hsdS sequences flanked by inverted repeats (referred to as epigenetic invertons) in certain R-M undergo invertase-catalyzed inversions. Previous studies Streptococcus pneumoniae have shown that inversions within clonal populations produce subpopulations with profound differences the methylome, cellular physiology virulence. In this study,...
ABSTRACT The interception of blood-borne bacteria in the liver defines outcomes invasive bacterial infections, but mechanisms this anti-bacterial immunity are largely speculative. This study shows that natural antibodies (nAbs) to capsules enable macrophage Kupffer cells (KCs) rapidly capture and kill encapsulated mice. Affinity pulldown with serotype-10A capsular polysaccharides (CPS10A) S. pneumoniae ( Spn 10A) led identification CPS10A-binding nAbs serum. CPS10A-antibody interaction...
Reversible or phenotypic tolerance to antibiotics within microbial populations has been implicated in treatment failure of chronic infections and development persister cells. However, the molecular mechanisms regulating drug are largely unknown. In this study, we identified a four-gene operon Streptococcus pneumoniae that contributes vancomycin (ptv). RNA sequencing, quantiative reverse transcriptase PCR, transcriptional luciferase reporter experiments revealed transcription ptv (consisting...
Francisella tularensis is the causative agent of tularemia and a category A bioterrorism agent. The molecular basis for extreme virulence remains unclear. Our recent study found that capBCA, three neighboring genes, are necessary infection F. live vaccine strain (LVS) in respiratory mouse model. We here show capBCA genes vivo growth LVS lungs, spleens, livers BALB/c mice. Unmarked deletion type Schu S4 resulted significant attenuation although level was much less profound than LVS. further...
Streptococcus pneumoniae is a major pathogen of human infections with the capacity for adaptation to host environments, but molecular mechanisms behind this phenomenon remain unclear. Previous studies reveal that pneumococcus extends epigenetic and phenotypic diversity by DNA inversions in three methyltransferase hsdS genes cod locus. This work revealed only gene same orientation as hsdM actively transcribed, other two are silent, serving sources inversions. While most catalyzed PsrA...