- Toxoplasma gondii Research Studies
- Parasitic Infections and Diagnostics
- Cytomegalovirus and herpesvirus research
- Antimicrobial Resistance in Staphylococcus
- Herpesvirus Infections and Treatments
- Antibiotic Resistance in Bacteria
- Escherichia coli research studies
- Plant Virus Research Studies
- Coccidia and coccidiosis research
- Microbial Natural Products and Biosynthesis
- Pneumonia and Respiratory Infections
- Bacteriophages and microbial interactions
- Legume Nitrogen Fixing Symbiosis
- Biochemical and Molecular Research
- Bacterial Infections and Vaccines
- Urinary Tract Infections Management
- Plant nutrient uptake and metabolism
- Cancer therapeutics and mechanisms
- Genomics and Phylogenetic Studies
- Antifungal resistance and susceptibility
- Viral gastroenteritis research and epidemiology
- Transgenic Plants and Applications
- Bacterial biofilms and quorum sensing
- Electrowetting and Microfluidic Technologies
- Infective Endocarditis Diagnosis and Management
Pfizer (United States)
2013-2025
Pearl River Community College
2012-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2004-2015
Bond University
2012
Merck (Japan)
2012
University of Pennsylvania
1994-2007
Walter and Eliza Hall Institute of Medical Research
1998
The University of Melbourne
1998
University of California, Berkeley
1993-1997
South University
1997
A vestigial, nonphotosynthetic plastid has been identified recently in protozoan parasites of the phylum Apicomplexa. The apicomplexan plastid, or “apicoplast,” is indispensable, but complete sequence both Plasmodium falciparum and Toxoplasma gondii apicoplast genomes offered no clue as to what essential metabolic function(s) this organelle might perform parasites. To investigate possible functions apicoplast, we sought identify nuclear-encoded genes whose products are targeted . We describe...
A nonhomologous integration vector was used to identify the Toxoplasma gondii hypoxanthine-xanthine-guanine phosphoribosyl transferase (HXGPRT) gene by insertional mutagenesis. Parasite mutants resistant 6-thioxanthine arose at a frequency of ∼3 × 10−7. Genomic DNA flanking insertion sites retrieved marker rescue and molecular clones exhibiting unambiguous homology H(X)GPRT genes from other species. Sequence analysis vector/genome junction reveals that linearized occurred with minimal...
To facilitate genetic analysis of the protozoan parasite Toxoplasma gondii, sequences derived from parasite's fused dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene have been used to produce vectors suitable for stable molecular transformation. Mutations introduced into DHFR coding region by analogy with pyrimethamine-resistant malaria confer drug resistance Toxoplasma, providing useful information on structure DHFR-TS enzymes and a powerful selectable marker studies. Depending...
Nonhomologous integration vectors have been used to demonstrate the feasibility of insertional mutagenesis in haploid tachyzoites protozoan parasite Toxoplasma gondii. Mutant clones resistant 5-fluorouracil were identified at a frequency approximately 10(-6) (approximately 2 x 10(-5) stable transformants). Four independent mutants isolated, all which shown lack uracil phosphoribosyl-transferase (UPRT) activity and harbor transgenes integrated closely linked loci, suggesting inactivation...
Group B streptococcus (GBS) causes serious diseases in newborn infants, often resulting lifelong neurologic impairments or death. Prophylactic vaccination of pregnant women prior to delivery could provide comprehensive protection, as early onset and late-onset disease maternal complications potentially be addressed. Capsular polysaccharide conjugate vaccine GBS6 was designed using surveillance data yielded by whole-genome sequencing a global collection recently recovered GBS isolates...
Adhesion of E. coli to the urinary tract epithelium is a critical step in establishing infections. FimH an adhesin positioned on fimbrial tip which binds mannosylated proteins via its lectin domain (FimH LD ). interest as target vaccines prevent infections (UTI). Previously, difficulties obtaining purified recombinant from along with poor inherent immunogenicity have hindered development effective vaccine candidates. To overcome these challenges, we devised novel production method using...
The trisubstituted pyrrole 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H-pyrrol-3-yl]pyridine (Compound 1) inhibits the growth of Eimeria spp. bothin vitro and in vivo. molecular target Compound 1 was identified as cGMP-dependent protein kinase (PKG) using a tritiated analogue to purify ∼120-kDa from lysates tenella. This represents first example protozoal PKG. Cloning PKG several Apicomplexan parasites has parasite signature sequence nearly 300 amino acids that is not found mammalian...
The hypoxanthine-xanthine-guanine phosphoribosyl transferase (HXGPRT) gene of the protozoan parasite Toxoplasma gondii encodes a safe, practical genetic marker suitable for both positive and negative selection. Taking advantage ability to control homologous versus nonhomologous recombination in haploid T. tachyzoites by manipulating length DNA sequence, we have explored possibility 'hit-and-run' mutagenesis introduce knock-outs (or allelic replacements) at loci which no known selection or...
ABSTRACT The trisubstituted pyrrole 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H-pyrrol-3-yl]pyridine (compound 1) has in vivo activity against the apicomplexan parasites Toxoplasma gondii and Eimeria tenella animal models. presumptive molecular target of this compound E. is cyclic GMP-dependent protein kinase (PKG). Native PKG purified from T. kinetic pharmacologic properties similar to those homologue, both have been functionally expressed as recombinant proteins . Computer...
We investigated potential targets for the activity of protein synthesis inhibitors against protozoan parasite Toxoplasma gondii. Although nanomolar concentrations azithromycin and clindamycin prevent replication T. gondii in both cell culture vivo assays, no inhibition labeling was observed either extracellular or intracellular parasites treated with up to 100 microM drug 24 h. Quantitative analysis > 300 individual spots on two-dimensional gels revealed proteins selectively depleted by...
The Clostridium difficile toxins A and B are primarily responsible for symptoms of C. associated disease prime targets vaccine development. We describe a plasmid-based system the production genetically modified in non-sporulating strain that lacks toxin genes tcdA tcdB. TcdA TcdB mutations targeting established glucosyltransferase cytotoxicity determinants were introduced into recombinant plasmids episomally expressed mutants purified from transformants. lacking autoproteolytic processing...
ABSTRACT Bivalent rLP2086 (Trumenba), a vaccine for prevention of Neisseria meningitidis serogroup B (NmB) disease, was licensed use in adolescents and young adults after it demonstrated that elicits antibodies initiate complement-mediated killing invasive NmB isolates serum bactericidal assay with human complement (hSBA). The consists two factor H binding proteins (fHBPs) representing divergent subfamilies to ensure broad coverage. Although is the surrogate efficacy, an hSBA not suitable...
We have exploited a variety of molecular genetic, biochemical, and genomic techniques to investigate the roles purine salvage enzymes in protozoan parasite Toxoplasma gondii. The ability generate defined genetic knockouts target transgenes specific loci demonstrates that T. gondii uses two (and only two) pathways for salvage, by hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) adenosine kinase (AK). Both HXGPRT AK are single-copy genes, either one can be deleted, indicating...
Toxoplasma is a significant opportunistic pathogen in AIDS, and bradyzoite differentiation the critical step pathogenesis of chronic infection. Bradyzoite development has an apparent tropism for cells tissues central nervous system, suggesting need specific molecular environment host cell, but it unknown whether this parasite directed or result features to cell itself. We have determined that trisubstituted pyrrole acts directly on human murine slow tachyzoite replication induce...