A5025807967- Fungal Infections and Studies
- Antifungal resistance and susceptibility
- Plant-Microbe Interactions and Immunity
- Plant Pathogens and Fungal Diseases
- Plant Disease Resistance and Genetics
- Nail Diseases and Treatments
- Toxin Mechanisms and Immunotoxins
- Phytoplasmas and Hemiptera pathogens
- Microbial Natural Products and Biosynthesis
- Photosynthetic Processes and Mechanisms
- Infectious Diseases and Mycology
- Mycotoxins in Agriculture and Food
- Fungal Biology and Applications
- Amino Acid Enzymes and Metabolism
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Fungal and yeast genetics research
- Soybean genetics and cultivation
- Yeasts and Rust Fungi Studies
- Microbial Metabolism and Applications
- T-cell and Retrovirus Studies
- Legume Nitrogen Fixing Symbiosis
- Galectins and Cancer Biology
- Cytomegalovirus and herpesvirus research
- Plant nutrient uptake and metabolism
- Streptococcal Infections and Treatments
National Institute of Allergy and Infectious Diseases
2015-2024
National Institutes of Health
2012-2024
Tianjin Third Central Hospital
2024
Tianjin Medical University
2024
Tianjin International Joint Academy of Biomedicine
2024
RELX Group (Netherlands)
2017
Children's Hospital of Los Angeles
2016
AT Sciences (United States)
2016
National Institute of Health Sciences
2003
Johns Hopkins University
2003
CC chemokine receptor 1 (CCR1) is expressed in neutrophils, monocytes, lymphocytes, and eosinophils, binds the leukocyte chemoattractant hematopoiesis regulator macrophage inflammatory protein (MIP)-1α, as well several related chemokines. Four other CCR subtypes are known; their specificities overlap with, but not identical to, CCR1, suggesting that CCR1 has both redundant specific biologic roles. To test this, we have developed CCR1-deficient mice (−/−) by targeted gene disruption. Although...
Cryptococcus neoformans is a haploid environmental organism and the major cause of fungal meningoencephalitis in AIDS patients. Fluconazole (FLC), triazole, widely used for maintenance therapy cryptococcosis. Heteroresistance to FLC, an adaptive mode azole resistance, was associated with FLC failure cases but mechanism underlying resistance unknown. We comparative genome hybridization quantitative real-time PCR order show that C. adapts high concentrations by duplication multiple...
Capsule formation plays a significant role in the pathogenicity of Cryptococcus neoformans. To study molecular basis capsule synthesis, capsule-deficient phenotype mutant strain was complemented by transformation. A plasmid rescued from resulting Cap+ transformant cap59 mutation which mapped previously classical recombination analysis. Gene deletion homologous integration resulted an acapsular phenotype, indicating that we have identified CAP59 gene. The gene assigned to chromosome I...
Cryptococcosis is a potentially lethal disease of humans/animals caused by Cryptococcus neoformans and gattii. Distinction between the two species based on phenotypic genotypic characteristics. Recently, it was proposed that C. be divided into gattii five phylogenetic analysis 115 isolates. While this proposal adds to knowledge about genetic diversity population structure cryptococcosis agents, published genotypes 2,606 strains have already revealed more than encompassed seven species....
Aspergillus fumigatus, a filamentous fungus producing bluish-green conidia, is an important opportunistic pathogen that primarily affects immunocompromised patients. Conidial pigmentation of A. fumigatus significantly influences its virulence in murine model. In the present study, six genes, forming gene cluster spanning 19 kb, were identified as involved conidial pigment biosynthesis fumigatus. Northern blot analyses showed genes to be developmentally regulated and expressed during...
ABSTRACT Aspergillus fumigatus , an important opportunistic pathogen which commonly affects neutropenic patients, produces conidia with a bluish-green color. We identified gene, alb1 is required for conidial pigmentation. The gene encodes putative polyketide synthase, and disruption of resulted in albino phenotype. Expression developmentally regulated, the 7-kb transcript detected only during conidiation stage. mutation was found to block 1,3,6,8-tetrahydroxynaphthalene production,...
Capsule formation plays a significant role in the pathogenicity of Cryptococcus neoformans. To study molecular basis capsule synthesis, capsule-deficient phenotype mutant strain was complemented by transformation. A plasmid rescued from resulting Cap+ transformant cap59 mutation which mapped previously classical recombination analysis. Gene deletion homologous integration resulted an acapsular phenotype, indicating that we have identified CAP59 gene. The gene assigned to chromosome I...
Cryptococcal meningoencephalitis develops as a result of hematogenous dissemination inhaled Cryptococcus neoformans from the lung to brain. The mechanism(s) by which C. crosses blood-brain barrier (BBB) is key unresolved issue in cryptococcosis. We used both an vivo mouse model and vitro human BBB investigate cryptococcal association with traversal BBB. Exposure brain microvascular endothelial cells (HBMEC) triggered formation microvillus-like membrane protrusions within 15 30 min. Yeast...
The extracellular polysaccharide capsule produced by Cryptococcus neoformans is essential for its pathogenicity. We have isolated and characterized a gene, (AP64, which required formation. An encapsulated strain created complementation of the cap64 mutation fatal infection mice within 25 days, while acapsular was avirulent. Gene deletion CAP64 from wild-type resulted in loss as well virulence. Contour-clamped homogeneous electric field gel analysis indicates that located on chromosome III...
Gliotoxin is an immunosuppressive mycotoxin long suspected to be a potential virulence factor of Aspergillus fumigatus. Recent studies using mutants lacking gliotoxin production, however, suggested that the not important for pathogenesis A. fumigatus in neutropenic mice resulting from treatment with cyclophosphomide and hydrocortisone. In this study, we report on pathobiological role two different mouse strains, 129/Sv BALB/c, were immunosuppressed by hydrocortisone alone avoid neutropenia....
Summary Cryptococcus neoformans is an environmental pathogen requiring atmospheric levels of oxygen for optimal growth. Upon inhalation, C. disseminates to the brain and causes meningoencephalitis, but mechanisms by which adapts low‐oxygen environment in have not been investigated. We found that SRE1 , a homologue mammalian sterol regulatory element‐binding protein (SREBP), functions oxygen‐sensing pathway. Low decreased synthesis triggered activation membrane‐bound Sre1p cleavage‐activating...
ABSTRACT A polysaccharide capsule is one of the most important virulence factors for pathogenic fungus Cryptococcus neoformans . We previously characterized two capsule-associated genes, CAP59 and CAP64 To further dissect molecular mechanism synthesis, 16 acapsular mutants induced by 4-nitroquinoline-1-oxide were obtained. The phenotype these was complemented. cloned gene designated CAP60 , deletion this newly described resulted in an phenotype. proposed 67-kDa Cap60p contains 592 amino...
Abstract Aspergillus fumigatus, a common mold, rarely infects humans, except during prolonged neutropenia or in cases of chronic granulomatous disease (CGD), primary immunodeficiency caused by mutations the NADPH oxidase that normally produces fungicidal reactive oxygen species. Filamentous hyphae are killed normal, but not CGD polymorphonuclear leukocytes (PMN); however, few studies on PMN-mediated host defenses against infectious conidia (spores) this organism have yielded conflicting...
In 1999, heteroresistance to triazoles was reported in Cryptococcus neoformans strains isolated from an azole therapy failure case of cryptococcosis AIDS patient and a diagnostic strain non-AIDS patient. this study, we analyzed 130 C. clinical environmental sources before 1979, prior the advent triazoles, 16 fluconazole (FLC)-resistant patients undergoing FLC maintenance during 1990 2000. All 1979 manifested (subset population that grows presence FLC) at concentrations between 4 64...
Cryptococcosis is caused by the opportunistic pathogen Cryptococcus neoformans or primary gattii. Epidemiological studies suggest that patients infected with C. gattii mainly present pulmonary disease, while those commonly manifest meningoencephalitis. We compared pathogenesis of two species using H99 and R265 strains in a murine inhalation model. grew faster brain death meningoencephalitis, lungs without producing fulminating Despite consistent failure to recover cells from blood, fraction...
ABSTRACT Cryptococcus neoformans strains resistant to azoles due mutations causing alterations in the ERG11 gene, encoding lanosterol 14α-demethylase, have rarely been reported. In this study, we characterized a C. serotype A strain that is high concentrations of fluconazole (FLC). This strain, which was isolated from an FLC-treated patient, contained five missense gene compared sequence reference H99. Molecular manipulations coupled with susceptibility triazole revealed single mutation...
Cryptococcal meningoencephalitis is the most common fungal disease in central nervous system. The mechanisms by which Cryptococcus neoformans invades brain are largely unknown. In this study, we found that C. neoformans-derived microvesicles (CnMVs) can enhance traversal of blood-brain barrier (BBB) vitro. immunofluorescence imaging demonstrates CnMVs fuse with human microvascular endothelial cells (HBMECs), constituents BBB. This activity presumably due to ability activate HBMEC membrane...
We have previously reported that Cryptococcus neoformans strains are innately heteroresistant to fluconazole in vitro, producing minor, highly resistant subpopulations due adaptive formation of disomic chromosomes. Using a mouse model, we assessed the emergence clones brain during treatment and found occurrence vivo with chromosomal disomy is strain dependent. Interestingly, was unrelated strain's MIC fluconazole.
We discovered a new lineage of the globally important fungal pathogen Cryptococcus gattii on basis analysis six isolates collected from three locations spanning Central Miombo Woodlands Zambia, Africa. All were environments (middens and tree holes) that are associated with small mammal, African hyrax. Phylogenetic population genetic analyses confirmed these form distinct, deeply divergent lineage, which we name VGV. VGV comprises two subclades (A B) capable causing mild lung infection...
The fungal pathogen Cryptococcus neoformans has a predilection for the central nervous system (CNS), resulting in devastating meningoencephalitis. At present, it is unclear how C. traverses blood–brain barrier (BBB) and causes CNS infection. present study examined characterized interaction of with human brain microvascular endothelial cells (HBMEC), which constitute BBB. Adhesion transcytosis HBMEC by was inoculum- time-dependent occurred both encapsulated acapsulated strains. induced marked...
ABSTRACT Cryptococcus neoformans is a pathogenic fungus which most commonly affects the central nervous system and causes fatal meningoencephalitis primarily in patients with AIDS. This produces thick extracellular polysaccharide capsule well recognized as virulence factor. Here, we describe isolation characterization of novel gene, CAP10 , required for formation. Complementation acapsular cap10 mutant produced an encapsulated strain deletion from wild resulted phenotype. The molecular mass...
The Cryptococcus neoformans STE12alpha gene, a homologue of Saccharomyces cerevisiae STE12, exists only in mating type (MAT)alpha cells. In S. cerevisiae, STE12 was required for and filament formation. C. neoformans, haploid fruiting on agar STE12alpha. ability to form hyphae, however, not affected by deletion when convergently growing MATa strains were present. Furthermore, ste12alpha disruptants fertile mated with strains, albeit reduced frequency. Most importantly, the virulence...
Chain lengths and cyclization patterns of microbial polyketides are generally determined by polyketide synthases alone. Fungal melanins often derived from a pentaketide 1,8-dihydroxynaphthalene, used for synthesis the upstream precursor, 1,3,6,8-tetrahydroxynaphthalene (1,3,6,8-THN). However,<i>Aspergillus fumigatus</i>, human fungal pathogen, uses heptaketide synthase (Alb1p) to synthesize its conidial pigment through pathway similar that which produces 1,8-dihydroxynaphthalene-melanin. In...
ABSTRACT Agrobacterium tumefaciens was used to transform Aspergillus fumigatus by either random or site-directed integration of transforming DNA (T-DNA). Random mutagenesis via -mediated transformation (ATMT) accomplished with T-DNA containing a hygromycin resistance cassette. Cocultivation A. conidia and (1:10 ratio) for 48 h at 24°C resulted in high frequencies (>100 transformants/10 7 conidia). The majority transformants harbored randomly integrated single copy were mitotically stable....
Aspergillus fumigatus is the most common etiologic agent of invasive aspergillosis in immunocompromised patients. Several studies have addressed mechanism involved host defense but only few investigated pathogen's response to attack by cells. To our knowledge, this first study that investigates genes differentially expressed conidia vs hyphae A. neutrophils from healthy donors as well those with chronic granulomatous disease (CGD) which are defective production reactive oxygen...