Molecular Cloning and Characterization of a P38-Like Mitogen-Activated Protein Kinase from Echinococcus granulosus

Cystic echinococcosis (CE) treatment urgently requires a novel drug. The p38 mitogen-activated protein kinases (MAPKs) are a family of Ser/Thr protein kinases, but still have to be characterized in Echinococcus granulosus. We identified a 1,107 bp cDNA encoding a 368 amino acid MAPK protein (Egp38) in E. granulosus. Egp38 exhibits 2 distinguishing features of p38-like kinases: a highly conserved T-X-Y motif and an activation loop segment. Structural homology modeling indicated a conserved structure among Egp38, EmMPK2, and H. sapiens p38α, implying a common binding mechanism for the ligand domain and downstream signal transduction processing similar to that described for p38α. Egp38 and its phosphorylated form are expressed in the E. granulosus larval stages vesicle and protoscolices during intermediate host infection of an intermediate host. Treatment of in vitro cultivated protoscolices with the p38-MAPK inhibitor ML3403 effectively suppressed Egp38 activity and led to significant protoscolices death within 5 days. Treatment of in vitro-cultivated protoscolices with TGF-β1 effectively induced Egp38 phosphorylation. In summary, the MAPK, Egp38, was identified in E. granulosus, as an anti-CE drug target and participates in the interplay between the host and E. granulosus via human TGF-β1.

Grass height and transmission ecology of Echinococcus multilocularis in Tibetan communities, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Alveolar echinococcosis is a major zoonosis of public health significance in western China. Overgrazing was recently assumed as a potential risk factor for transmission of alveolar echinococcosis. The research was designed to further test the overgrazing hypothesis by investigating how overgrazing influenced the burrow density of intermediate host small mammals and how the burrow density of small mammals was associated with dog Echinococcus multilocularis infection.</p><p><b>METHODS</b>The study sites were chosen by previous studies which found areas where the alveolar echinococcosis was prevalent. The data, including grass height, burrow density of intermediate host small mammals, dog and fox fecal samples as well as Global Positioning System (GPS) position, were collected from field investigations in Shiqu County, Sichuan Province, China. The fecal samples were analyzed using copro-PCR. The worms, teeth, bones and hairs in the fecal samples were visually examined. Single factor and multifactor analyses tools including chi square and generalized linear models were applied to these data.</p><p><b>RESULTS</b>By using grass height as a proxy of grazing pressure in the homogenous pasture, this study found that taller grass in the pasture led to lower small mammals' burrow density (chi(2) = 4.670, P = 0.031, coefficient = -1.570). The Echinococcus multilocularis worm burden in dogs was statistically significantly related to the maximum density of the intermediate host Ochotona spp. (chi(2) = 5.250, P = 0.022, coefficient = 0.028). The prevalence in owned dogs was positively correlated to the number of stray dogs seen within a 200 meter radius (Wald chi(2) = 8.375, P = 0.004, odds ratio = 1.198).</p><p><b>CONCLUSIONS</b>Our findings support the hypothesis that overgrazing promotes transmission of alveolar echinococcosis and confirm the role of stray dogs in the transmission of alveolar echinococcosis.</p>

Impact of overgrazing on the transmission of Echinococcus multilocularis in Tibetan pastoral communities of Sichuan Province, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Overgrazing was assumed to increase the population density of small mammals that are the intermediate hosts of Echinococcus multilocularis, the pathogen of alveolar echinococcosis in the Qinghai Tibet Plateau. This research tested the hypothesis that overgrazing might promote Echinococcus multilocularis transmission through increasing populations of small mammal, intermediate hosts in Tibetan pastoral communities.</p><p><b>METHODS</b>Grazing practices, small mammal indices and dog Echinococcus multilocularis infection data were collected to analyze the relation between overgrazing and Echinococcus multilocularis transmission using nonparametric tests and multiple stepwise logistic regression.</p><p><b>RESULTS</b>In the investigated area, raising livestock was a key industry. The communal pastures existed and the available forage was deficient for grazing. Open (common) pastures were overgrazed and had higher burrow density of small mammals compared with neighboring fenced (private) pastures; this high overgrazing pressure on the open pastures measured by neighboring fenced area led to higher burrow density of small mammals in open pastures. The median burrow density of small mammals in open pastures was independently associated with nearby canine Echinococcus multilocularis infection (P = 0.003, OR = 1.048).</p><p><b>CONCLUSION</b>Overgrazing may promote the transmission of Echinococcus multilocularis through increasing the population density of small mammals.</p>