A5021498852- Reproductive tract infections research
- Gut microbiota and health
- Urinary Tract Infections Management
- Reproductive System and Pregnancy
- Clostridium difficile and Clostridium perfringens research
- Immune Response and Inflammation
- Vibrio bacteria research studies
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Escherichia coli research studies
- Adolescent Sexual and Reproductive Health
- Reproductive Physiology in Livestock
- Salmonella and Campylobacter epidemiology
- Ubiquitin and proteasome pathways
- Plant and fungal interactions
- Bladder and Urothelial Cancer Treatments
- Digestive system and related health
- Syphilis Diagnosis and Treatment
- Probiotics and Fermented Foods
- Fungal and yeast genetics research
- Toxoplasma gondii Research Studies
- Helicobacter pylori-related gastroenterology studies
- Cancer Research and Treatments
- Cervical Cancer and HPV Research
- Cystic Fibrosis Research Advances
Duke University
2016-2025
Duke University Hospital
2015-2025
Duke Medical Center
2015-2025
Oregon Health & Science University
2023
Umeå University
2023
Harvard University
2015
Office of the Director
2015
National Institutes of Health
2015
Rockefeller University
2009
Stanford University
1996-2005
We have constructed a library in Escherichia coli of mutant gfp genes (encoding green fluorescent protein, GFP) expressed from tightly regulated inducible promoter. introduced random amino acid (aa) substitutions the twenty aa flanking chromophore Ser-Tyr-Gly sequence at 65-67. then used fluorescence-activated cell sorting (FACS) to select variants GFP that fluoresce between 20-and 35-fold more intensely than wild type (wt), when excited 488 nm. Sequence analysis reveals three classes GFP....
Salmonella pathogenicity island 2 (SPI‐2) encodes a putative type III secretion system necessary for systemic infection in animals. We have investigated the transcriptional organization and regulation of SPI‐2 by creating gfp fusions throughout entire gene cluster. These demonstrated that genes encoding structural, regulatory previously uncharacterized secreted proteins are preferentially expressed intracellular environment host macrophage. Furthermore, transcription these within cells was...
A selection strategy was devised to identify bacterial genes preferentially expressed when a bacterium associates with its host cell. Fourteen Salmonella typhimurium genes, which were under the control of at least four independent regulatory circuits, identified be selectively induced in macrophages. Four encode virulence factors, including component type III secretory apparatus. This methodology should generally applicable identification from pathogenic organisms that are upon association...
The ability of Salmonella typhimurium to survive and replicate within murine macrophages is dependent on a low phagosomal pH. This requirement for an acidic vacuole suggests that pH important environmental stimulus the transcription genes necessary intracellular survival. To study behaviour acid‐inducible in response environment, we have applied novel enrichment strategy, termed differential fluorescence induction (DFI), screen S . library promoters are upregulated at 4.5. DFI utilizes...
The acquisition of host-derived lipids is essential for the pathogenesis obligate intracellular bacteria Chlamydia trachomatis . Current models chlamydial lipid center on fusion Golgi-derived exocytic vesicles and endosomal multivesicular bodies with bacteria-containing parasitophorous vacuole (“inclusion”). In this study, we describe a mechanism organelle subversion by C. We show live cell fluorescence microscopy electron that droplets (LDs), neutral storage organelles, are translocated...
ABSTRACT STING ( s t i mulator of interfero n [IFN] g enes) initiates type I IFN responses in mammalian cells through the detection microbial nucleic acids. The membrane-bound obligate intracellular bacterium Chlamydia trachomatis induces a STING-dependent response infected cells, yet IFN-inducing ligand remains unknown. In this report, we provide evidence that synthesizes cyclic di-AMP (c-di-AMP), acid metabolite not previously identified Gram-negative bacteria, and is prominent for...
The green fluorescent protein (GFP) from Aequorea victoria is a novel marker that has potential use in the study of bacterial pathogenicity. To explore some applications GFP to host-parasite interactions, we constructed two expression vectors suitable for different facultative intracellular pathogens. first vector was tested enteric pathogens, Salmonella typhimurium and Yersinia pseudotuberculosis, second Mycobacterium marinum (Mm). Both were found be stable direct high levels synthesis....
Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs GBPs stably associate with pathogen-containing vacuoles (PVs) elicit immune pathways directed at targeted vacuoles. Targeting PVs requires formation higher-order protein oligomers, a process negatively regulated by subclass IRG proteins called IRGMs. We found that paralogous IRGM Irgm1 Irgm3 fail robustly "non-self"...
Chlamydia trachomatis is an obligate intracellular pathogen responsible for ocular and genital infections of significant public health importance. C. undergoes a biphasic developmental cycle alternating between two distinct forms: the infectious elementary body (EB), replicative but non-infectious reticulate (RB). The molecular basis these transitions metabolic properties EB RB forms are poorly understood as bacteria have traditionally been difficult to manipulate through classical genetic...
Chlamydia trachomatis , a pathogen responsible for diseases of significant clinical and public health importance, remains poorly characterized because its intractability to routine molecular genetic manipulation. We have developed combinatorial approach rapidly generate comprehensive library genetically defined mutants. Chemical mutagenesis, coupled with whole-genome sequencing (WGS) system DNA exchange within infected cells, was used mutants distinct phenotypes, map the underlying lesions,...
Chlamydia trachomatis, the causative agent of trachoma and sexually transmitted infections, employs a type III secretion (T3S) system to deliver effector proteins into host epithelial cells establish replicative vacuole. Aside from phosphoprotein TARP, that promotes actin re-arrangements, very few factors mediating bacterial entry early inclusion establishment have been characterized. Like many T3S effectors, TARP requires chaperone (Slc1) for efficient translocation cells. In this study, we...