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C Su

Publications and source records attributed to C Su.

At least 19 recordsLinked to original sources
PubMed2006

A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii.

Toxoplasma gondii strains differ dramatically in virulence despite being genetically very similar. Genetic mapping revealed two closely adjacent quantitative trait loci on parasite chromosome VIIa that control the extreme virulence of the type I lineage. Positional cloning identified the candidate virulence gene ROP18, a highly polymorphic serine-threonine kinase that was secreted into the host cell during parasite invasion. Transfection of the virulent ROP18 allele into a nonpathogenic type III strain increased growth and enhanced mortality by 4 to 5 logs. These attributes of ROP18 required kinase activity, which revealed that secretion of effectors is a major component of parasite virulence.

Alleles↗
PubMed2006

Biologic and genetic comparison of Toxoplasma gondii isolates in free-range chickens from the northern Pará state and the southern state Rio Grande do Sul, Brazil revealed highly diverse and distinct parasite populations.

The prevalence of Toxoplasma gondii in 84 free-range chickens (34 from the northern Pará state, and 50 from Rio Grande do Sul, the southern state) from Brazil, South America was determined. Antibodies to T. gondii were assayed by the modified agglutination test (MAT), and found in 39 (46.4%) of 84 chickens with titers of 1:10 in one, 1:20 in two, 1:40 in four, 1:80 in seven, 1:160 in five, 1:320 in six, 1:640 in eight and > or =1:1280 in six. Hearts and brains of 45 chickens with titers of 1:20 or less were pooled and fed to two T. gondii-free cats. Hearts and brains of 39 chickens with titers of 1:10 or higher were bioassayed in mice. Feces of cats were examined for oocysts. One cat fed tissues from 31 chickens with titers of less than 1:10 from Rio Grande do Sul shed T. gondii oocysts. T. gondii was isolated by bioassay in mice from 33 chickens with MAT titers of 1:20 or higher. All infected mice from 10 isolates died of toxoplasmosis. All 34 isolates (15 from Pará, 19 from Rio Grande do Sul) were genotyped using 11 genetic markers including SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, a new SAG2 and Apico. Eleven genotypes were revealed for Pará isolates and seven genotypes for Rio Grande do Sul. No genotype was shared between the two geographical locations. These data suggest that T. gondii isolates are highly diverse and genetically distinct between the two different regions in Brazil that are 3500 km apart.

Animals↗
PubMed2006

Biologic and genetic characteristics of Toxoplasma gondii isolates in free-range chickens from Nicaragua, Central America.

The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator of the prevalence of T. gondii oocysts in the soil because chickens feed from the ground. The prevalence of T. gondii in 98 free-range chickens (Gallus domesticus) from Nicragua was determined. Antibodies to T. gondii were assayed by the modified agglutination test (MAT), and found in 84 (85.7%) of 98 chickens with titers of 1:5 in 10, 1:10 in eight, 1:20 in seven, 1:40 in nine, 1:80 in 11, 1:160 in one, 1:200 in 27, 1:400 in six, 1:800 four, and 1:3200 in one bird. Hearts and brains of 32 chickens with titers of 1:10 or less were pooled and fed to three T. gondii-free cats. Hearts and brains of 66 chickens with titers of 1:20 or higher were bioassayed in mice. Feces of cats were examined for oocysts. The cat fed tissues from eight chickens with titers of 1:10 shed T. gondii oocysts. The two cats fed tissues of 24 chickens with titers of 1:5 or less did not shed oocysts. T. gondii was isolated by bioassay in mice from 47 chickens with MAT titers of 1:20 or higher. All infected mice from six isolates died of toxoplasmosis. Overall, 41 of 170 (24.1%) mice that became infected after inoculation with chicken tissues died of toxoplasmosis. Genotyping of these 48 isolates (47 from mice and 1 from pooled tissues) using polymorphisms at the loci SAG1, SAG2, SAG3, BTUB and GRA6 revealed eight genotypes. Six isolates had Type I alleles, three isolate had Type II alleles and six isolates had Type III alleles at all loci. Four isolates had mixed infections. Two isolates have a unique allele at SAG1 locus and combination of I and III alleles at other loci. The rest 27 isolates contained the combination of Type I and III alleles and were divided into four genotypes. More than one genotypes were often isolated in chickens from the same household, indicating multiple genotypes were circulating in the same environment. This may explain the high frequency of mixed infections observed. High rate of mixed infection in intermediate hosts such as chickens may facilitate genetic exchange between different parasite lineages in definitive feline hosts. This is the first report of genetic characterization of T. gondii isolates from Nicragua, Central America.

Agglutination Tests↗
PubMed2006

Prevalence of Toxoplasma gondii in cats from Colombia, South America and genetic characterization of T. gondii isolates.

Cats are important in the epidemiology of Toxoplasma gondii infection because they are the only hosts that can excrete the environmentally-resistant oocysts. In the present study, prevalence of T. gondii was determined in serum, feces, and tissues of 170 unwanted cats from Colombia, South America. Antibodies to T. gondii were assayed by the modified agglutination test and found in 77 of 170 (45.2%) cats with titers of <1:5 in 93, 1:5 in eight, 1:10 in 17, 1:20 in 10, 1:40 in seven, 1:80 in four, 1:160 in eight, 1:320 in six, and 1:640 or higher in 17 cats. T. gondii oocysts were not found in feces of any cat as ascertained by bioassay in mice. Tissues (brain, heart, tongue) of 116 cats were bioassayed in mice or cats. T. gondii was isolated from tissues of 15 of the 42 cats with titers of 1:40 or higher and not from any of the 90 cats titers of 1:20 or lower. Of the 29 cats whose tissues were bioassayed individually, T. gondii was isolated from the tongues of nine, hearts of eight, and brains of five. Mice inoculated with tissues of 12 of 15 infected cats died of toxoplasmosis; with nine T. gondii isolates all infected mice died. Overall, 65 of 92 (70%) of T. gondii-infected mice died of toxoplasmosis. Genotyping of these 15 isolates using polymorphisms at the SAG1, SAG2, SAG3, BTUB, and GRA6 loci revealed that three isolates (TgCtCo1, 2, and 7) had Type I alleles and one isolate (TgCtCo8) had Type II allele at all five loci. Eleven isolates contained the combination of Type I and III alleles and were divided into three genotypes, with TgCtCo3,5,6,9,12,13 and 15 had alleles I, I, III, I and III, TgCtCo4,10,11 had alleles I, III, III, I and I, and TgCtCo14 had alleles I, III, III, III, and III, at loci SAG1, SAG2, SAG3, BTUB and GRA6, respectively. All infected mice from each group had identical genotype except one mouse infected with TgCtCo5 had a Type III allele at locus BTUB and a unique allele (u-1) at locus SAG1 indicating mixed infection for TgCtCo5, whereas the rest seven mice had a Type I alleles at both loci.

Agglutination Tests↗
PubMed2006

Genotypic changes in human immunodeficiency virus type 1 envelope glycoproteins on treatment with the fusion inhibitor enfuvirtide and their influence on changes in drug susceptibility in vitro.

BACKGROUND: Previous studies have established the importance of substitutions at amino acids 36-45 of HIV-1 gp41 in the development of viral resistance to the peptide fusion inhibitor enfuvirtide. However, the influence of other loci in the HIV-1 envelope is not well established. OBJECTIVE: To identify positions showing genotypic changes that are associated with particularly high levels of changes in enfuvirtide susceptibility. STUDY DESIGN: We examined full-length baseline and on treatment sequences of gp120 and gp41 for isolates from 369 patients in Phase III studies of enfuvirtide, including 281 patients receiving ENF+OB and 88 patients receiving OB alone. Individual changes in gp41 and gp120 were evaluated for correlations with on treatment phenotype changes by analysis of variance (ANOVA). This modeling was done with (two-way) and without (one-way) ANOVA adjusting for the effects of any changes in gp41 amino acids 36-45 modeled as a single variable (ANY(36-45)). Positions displaying significance levels of p<0.05 by either one- or two-way ANOVA were then studied by multi-way ANOVA (stepwise regression). RESULTS: In addition to changes at gp41 amino acids 36-45, changes at three positions in the HR2 domain (126, 129 and 133) occurred significantly more often in patients undergoing virologic failure on enfuvirtide. However, ANY(36-45) alone accounted for slightly more than 90% of the variation in phenotype explained by the ANOVA models. Relative to ANY(36-45) alone, significant increases in the geometric mean of the fold-change in inhibitory concentration (19.6-236.3-fold higher) were observed for amino acid changes at positions gp41: 18, 42,126, 247, 256 and 312; gp120: 330, 389 and 424 and significant reductions (18.8-29.7-fold lower) for gp41: 3, 46, 165, 232 and 324. CONCLUSIONS: This study represents a statistical approach to highlight positions in HIV envelope that undergo mutations in the presence of enfuvirtide. Several of the identified positions have been implicated in the viral fusion process by other studies. The specific impact of positions 330. Three hundred and eighty-nine and 424 on viral fusion kinetics remains to be studied further by site-directed mutagenesis experiments.

Amino Acid Sequence↗
PubMed2006

Characterization of Toxoplasma gondii isolates in free-range chickens from Chile, South America.

The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator of the prevalence of T. gondii oocysts in the soil because chickens feed from the ground. The prevalence of T. gondii in 85 free-range chickens (Gallus domesticus) from Chile was determined. Antibodies to T. gondii were assayed by the modified agglutination test (MAT), and found in 47 of 85 (55.3.9%) chickens with titers of 1:5 in six, 1:10 in four, 1:20 in four 1: 40 in three, 1: 80 in nine, 1: 160 in four 1:320 in nine, and 1: 640 or higher in eight. Hearts and brains of 47 chickens with titers of 1:5 or higher were pooled for each chicken and bioassayed in mice. Tissues from 16 seronegative (MAT<1:5) chickens were pooled and fed to one T. gondii-free cat. Feces of the cat were examined for oocysts but none was found based on bioassay of fecal floats in mice. Hearts and brains from seven seronegative (<1:5) were pooled and bioassayed in mice; T. gondii was not isolated. T. gondii was isolated by bioassay in mice from 22 chickens with MAT titers of 1:20 or higher. Genotyping of these 22 isolates using polymorphisms at the loci SAG1, SAG2, SAG3, BTUB and GRA6 revealed three genotypes. Seventeen isolates had type II alleles and four isolates had type III alleles at all loci. One isolate contained the combination of type I and III alleles. This is the first report of genetic characterization of T. gondii isolates from Chile, South America.

Agglutination Tests↗
PubMed2006

Genotyping of Toxoplasma gondii by multilocus PCR-RFLP markers: a high resolution and simple method for identification of parasites.

It was generally believed that Toxoplasma gondii had a clonal population structure with three predominant lineages, namely types I, II and III. This was largely based on genotyping of more than 100 T. gondii isolates originating from a variety of human and animal sources in North America and Europe. Recent genotyping studies on T. gondii strains from wild animals or human patients from different geographical regions revealed the high frequency of non-archetypal genotypes, suggesting the overall diversity of the T. gondii population might be much higher than we thought. However, as most genotyping studies had relied on a few biallelic markers, the resolution and discriminative power of identifying parasite isolates were quite low. To date, there is no commonly used set of markers to genotype T. gondii strains and it is not feasible to compare results from different laboratories. Here, we developed nine PCR-restriction fragment length polymorphism markers with each of them capable of distinguishing the three archetypal T. gondii alleles in one restriction-enzyme reaction by agarose gel electrophoresis. Genotyping 46 T. gondii isolates from different sources using these markers showed that they could readily distinguish the archetypal from atypical types and reveal the genetic diversity of the parasites. In addition, mixed strains in samples could be easily detected by these markers. Use of these markers will facilitate the identification of T. gondii isolates in epidemiological and population genetic studies.

Animals↗
PubMed2006

Biologic and genetic characteristics of Toxoplasma gondii isolates in free-range chickens from Costa Rica, Central America.

The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator of the prevalence of T. gondii oocysts in the soil because chickens feed from the ground. The prevalence of T. gondii in 144 free-range chickens (Gallus domesticus) from Costa Rica was determined. Antibodies to T. gondii were assayed by the modified agglutination test (MAT), and found in 60 (40.1%) of 144 chickens with titers of 1:5 in 16, 1:10 in 5, 1:20 in 2, 1:40 in 3, 1:80 in 5, and 1:160 or higher in 29. Tissues of all chickens were bioassayed for T. gondii in mice or cats. Hearts and brains of 52 chickens with titers of 1:5 or higher and 16 chickens with doubtful titers were pooled and bioassayed in mice. Tissues from 76 chickens with MAT titers of 1:10 or less were pooled and fed to three T. gondii-free cats. Fecal floats of cats were bioassayed orally in mice but were negative for T. gondii oocysts. T. gondii was isolated by bioassay in mice from 32 chickens with MAT titers of 1:10 or higher. All infected mice from 4 of the 32 isolates died of toxoplasmosis. Genotyping of these 32 isolates using polymorphisms at the loci SAG1, SAG2, SAG3, BTUB and GRA6 revealed five genotypes. Five isolates had type I alleles and one isolate had type III alleles at all loci. The rest 26 isolates contained the combination of type I and II or I and III alleles and were divided into three genotypes. None was found to have genotype II alleles at all five loci. This is the first report of genetic characterization of T. gondii isolates from Costa Rica, Central America.

Agglutination Tests↗
PubMed2005

Genotyping of Toxoplasma gondii strains from immunocompromised patients reveals high prevalence of type I strains.

Toxoplasma gondii is an important food- and waterborne opportunistic pathogen that causes severe disease in immunocompromised patients. T. gondii has an unusual clonal population structure consisting of three widespread lineages known as I, II, and III. To establish the genotypes of strains of T. gondii associated with human toxoplasmosis, we have developed a set of four highly sensitive and polymorphic nested PCR markers. Multiplex nested PCR analysis was used to genotype parasites in cerebral spinal fluid samples from 8 of 10 human immunodeficiency virus-positive patients. Remarkably, a majority of these patients had infections with type I strains or strains containing type I alleles, despite the fact that this lineage is normally uncommon in humans and animals. Multiplex analysis of these four unlinked makers was able to distinguish all three common genotypes and also detected two strains with mixed genotypes. Further analysis based on sequencing of a polymorphic intron revealed that one of these recombinant strains was an exotic lineage distinct from the archetypal clonal lineages. The multiplex nested PCR analysis described here will be useful for analyzing the contribution of parasite genotype to toxoplasmosis.

AIDS-Related Opportunistic Infections↗
PubMed2004

Genetic diversity, clonality and sexuality in Toxoplasma gondii.

The majority of Toxoplasma gondii strains from a variety of human and animal sources have been grouped into three highly clonal but closely related lineages. The low occurrence of nucleotide differences among the three predominant lineages and their unusual dimorphic allelic composition suggest that they have arisen from a recent common ancestry. Less than 1% of the previously studied strains contain unique genotypes and high divergence of DNA sequence, and therefore are considered 'exotic' or 'atypical' strains. The seemingly low genetic diversity in T. gondii may have been underestimated because most parasite strains in previous studies were collected from human patients and domestic animals in North America and Europe. To investigate the genetic diversity of T. gondii, we analysed parasite strains isolated from remote geographical regions by multilocus microsatellite sequencing and phylogenetic analysis. The genetic diversity indices, the molecular analysis of microsatellite genotypes and the constructed phylogram considered together suggest that the global T. gondii population is highly diversified and not characteristic of a clonal organism. The most parsimonious hypothesis is that T. gondii presents a complex population structure with a mix of clonal and sexual propagation as a function of the environmental conditions. The comparison between domestic strains data on one hand and wild strains data on the other hand is in favour of more frequent sexual recombinations in wild environment even though Toxoplasma subpopulation in human and domestic animals is largely clonal.

Animal Diseases↗
PubMed2003

Recent expansion of Toxoplasma through enhanced oral transmission.

The global predominance of three clonal Toxoplasma gondii lineages suggests that they are endowed with an exceptional trait responsible for their current parasitism of nearly all warm-blooded vertebrates. Genetic polymorphism analyses indicate that these clonal lineages emerged within the last 10,000 years after a single genetic cross. Comparison with ancient strains (approximately 1 million years) suggests that the success of the clonal lineages resulted from the concurrent acquisition of direct oral infectivity. This key adaptation circumvented sexual recombination, simultaneously promoting transmission through successive hosts, hence leading to clonal expansion. Thus, changes in complex life cycles can occur rapidly and can profoundly influence pathogenicity.

Animals↗
PubMed2003

IFN-gamma is associated with risk of Schistosoma japonicum infection in China.

Before the start of the schistosomiasis transmission season, 129 villagers resident on a Schistosoma japonicum-endemic island in Poyang Lake, Jiangxi Province, 64 of whom were stool-positive for S. japonicum eggs by the Kato method and 65 negative, were treated with praziquantel. Forty-five days later the 93 subjects who presented for follow-up were all stool-negative. Blood samples were collected from all 93 individuals. S. japonicum soluble worm antigen (SWAP) and soluble egg antigen (SEA) stimulated IL-4, IL-5 and IFN-gamma production in whole-blood cultures were measured by ELISA. All the subjects were interviewed nine times during the subsequent transmission season to estimate the intensity of their contact with potentially infective snail habitats, and the subjects were all re-screened for S. japonicum by the Kato method at the end of the transmission season. Fourteen subjects were found to be infected at that time. There was some indication that the risk of infection might be associated with gender (with females being at higher risk) and with the intensity of water contact, and there was evidence that levels of SEA-induced IFN-gamma production were associated with reduced risk of infection.

Adolescent↗
PubMed2003

Differential expression of the lactose transporter gene affects growth of Staphylococcus aureus in milk.

In this study, differential display polymerase chain reaction (PCR) was used to search for unique or enhanced expression of genes in prevalent bovine mastitis-causing Staphylococcus aureus strains. Comparison of a pair of prevalent and rare strains revealed the differential expression of several genes. The lactose-specific permease, enzyme II (EII), was highly expressed in the prevalent strain. This gene was selected for further study due to its potential influence on bacterial growth, because lactose is the primary carbohydrate in milk. Growth analysis illustrated that prevalent strains reach significantly higher growth densities sooner than rare strains. Quantitative competitive reverse transcription PCR (QC RT-PCR) revealed increased EII mRNA expression in prevalent strains as compared to rare strains. Mutation of the EII gene resulted in abrogated growth and decreased EII mRNA expression in media containing lactose. These data suggest that increased EII expression may facilitate the pathogenesis of S. aureus mastitis by enhancing growth. This study is the first to implicate EII as a potential virulence factor in mastitis, and therefore may be useful in the development of novel therapeutic strategies against S. aureus mastitis.

Animals↗
PubMed2002

Down-regulation of specific antigen-driven cytokine production in a population with endemic Schistosoma japonicum infection.

Schistosome antigen-driven cytokine responses and antischistosome antibody levels of residents of a Schistosoma japonicum endemic island in Poyang Lake, Jiangxi Province were studied before and 45 days after treatment with praziquantel. IL-4, IL-5, IL-10 and INF-gamma were all detected in the supernatants of whole-blood cultures after stimulation with schistosome soluble egg antigen (SEA) and soluble worm antigen preparation (SWAP). The percentages of subjects producing detectable amounts of each cytokine assayed were higher in the group who were negative by stool examination at the start of the study than in those who were initially stool positive. After praziquantel treatment the percentages of subjects producing both type I and type II cytokines increased. This suggests that the production of both types of cytokine was down-regulated in the presence of live, egg-laying S. japonicum adult worms but that this was reversible by treatment. In contrast, the antibody studies showed higher levels of SWAP and SEA-specific antibodies (IgE, total IgG, IgG4, IgM) in subjects who were originally stool-positive than in those who were stool-negative. After treatment specific IgE responses were elevated, but total IgG and IgG4 anti-SEA and IgM anti-SWAP antibody levels all fell significantly.

Adolescent↗
PubMed2001

Arsenate and arsenite removal by zerovalent iron: effects of phosphate, silicate, carbonate, borate, sulfate, chromate, molybdate, and nitrate, relative to chloride.

Batch tests were performed to evaluate the effects of inorganic anion competition on the kinetics of arsenate (As(V)) and arsenite (As(III)) removal by zerovalent iron (Peerless Fe0) in aqueous solution. The oxyanions underwent either sorption-dominated reactions (phosphate, silicate, carbonate, borate, and sulfate) or reduction-dominated reactions (chromate, molybdate, and nitrate) with Peerless Fe0 in the presence of As(V) or As(III), relative to chloride. Pseudo-first-order rate equations were found to describe satisfactorily both As(V) and As(III) removal kinetics in the presence of each competing anion. Of the oxyanions tested for Peerless Fe0 in the pH range from 7 to 9, phosphate caused the greatest decrease in As removal rate (7.0 x 10(-3) to 18.5 x 10(-3) h(-1)) relative to chloride (34.9 x 10(-3) to 36.2 x 10(-3) h(-1)). Silicate, chromate, and molybdate also caused strong inhibition of As removal, followed by carbonate and nitrate, whereas borate and sulfate only caused slight inhibition to As(III) removal. Present results show that Peerless Fe0 may be an excellent permeable reactive barrier medium for a suite of mixed inorganic contaminants. The anion competing effects should be considered when designing permeable reactive barriers composed of zerovalent iron for field applications to remediate As(V) and As(III).

Adsorption↗
PubMed2001

Arsenate and arsenite removal by zerovalent iron: kinetics, redox transformation, and implications for in situ groundwater remediation.

Batch tests were performed utilizing four zerovalent iron (Fe0) filings (Fisher, Peerless, Master Builders, and Aldrich) to remove As(V) and As(III) from water. One gram of metal was reacted headspace-free at 23 degrees C for up to 5 days in the dark with 41.5 mL of 2 mg L(-1) As(V), or As(III) or As(V) + As(III) (1:1) in 0.01 M NaCl. Arsenic removal on a mass basis followed the order: Fisher > Peerless Master Builders > Aldrich; whereas, on a surface area basis the order became: Fisher > Aldrich > Peerless Master Builders. Arsenic concentration decreased exponentially with time, and was below 0.01 mg L(-1) in 4 days with the exception of Aldrich Fe0. More As(III) was sorbed than As(V) by Peerless Fe0 in the initial As concentration range between 2 and 100 mg L(-1). No As(III) was detected by X-ray photoelectron spectroscopy (XPS) on Peerless Fe0 at 5 days when As(V) was the initial arsenic species in the solution. As(III) was detected by XPS at 30 and 60 days present on Peerless Fe0, when As(V) was the initial arsenic species in the solution. Likewise, As(V) was found on Peerless Fe0 when As(II) was added to the solution. A steady distribution of As(V) (73-76%) and As(III) (22-25%) was achieved at 30 and 60 days on the Peerless Fe0 when either As(V) or As(III) was the initial added species. The presence of both reducing species (Fe0 and Fe2+) and an oxidizing species (MnO2) in Peerless Fe0 is probably responsible for the coexistence of both As(V) and As(III) on Fe0 surfaces. The desorption of As(V) and As(III) by phosphate extraction decreased as the residence time of interaction between the sorbents and arsenic increased from 1 to 60 days. The results suggest that both As(V) and As(III) formed stronger surface complexes or migrated further inside the interior of the sorbent with increasing time.

Adsorption↗
PubMed2001

Assignment of EPR Transitions in a Manganese-Containing Lipoxygenase and Prediction of Local Structure.

A new variant of lipoxygenases, one containing manganese instead of iron, is characterized by electron paramagnetic resonance (EPR) at two frequencies. In the manganous state (S(e) = 5/2), maganese lipoxygenase (MnLO) yields very broad X-band (9.2 GHz) EPR signals, extending over about 800 mT. In contrast, at W-band (94 GHz), the signal is much simplified, consisting of nested transitions centered near the free electron g-value. Computer simulation has been employed to derive estimates of the zero-field splittings for MnLO, with data from these two EPR frequencies. The general features of both X- and W-band spectra are fit, first, by simulations with S(e) = 5/2, but no nuclear hyperfine splitting. The simulations are then refined by inclusion of the hyperfine splitting. On the basis of the simulations, the ranges of zero-field splitting parameters are D = +0.07 to +0.10 cm(-1), and E/D = 0.13 to 0.23. Comparison of the value of D for MnLO with that of other manganese-containing proteins suggests that MnLO has three N-ligands to the metal center and O-ligands in the remainder of 6 coordination positions. The coordination environment of MnLO is similar to that in iron lipoxygenases.

Journal Article↗