Project description:Pythiosis is a deadly infectious disease of humans and animals living in tropical and subtropical countries. The causative agent is the oomycete Pythium insidiosum. Treatment of pythiosis is challenging. Therefore, protein profiling could generate the important information for further drug development.
Project description:Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, a chronic granulomatous disease. Mtb is mostly restricted to humans and seldom causes disease in animals. M. bovis (Mbv) on the other hand causes tuberculosis in cows (bovine tuberculosis) and several wild animals. Each of these pathogens therefore has unique host adaptations and the host- and pathogen-specific factors driving this differential tropism still remain largely unknown. Here we profiled the secretomes of Mtb- and Mbv-infected bovine macrophages to characterise host-specific responses to each pathogen.
Project description:Fungal diseases significantly impact human mortality and morbidity. However, despite the number of annual deaths caused by fungi exceeding 1.6 million, these microorganisms are often neglected. Fonsecaea pedrosoi is the main etiologic agent of chromoblastomycosis (CBM), a chronic mycosis that affects the skin and subcutaneous tissue that, in 2017, was included in the WHO list of neglected tropical diseases. It is essentially an occupational disease that affects individuals in poverty, causing significant morbidity and mortality. CBM is a disease of global distribution, and most cases are described in tropical and subtropical regions of America, Africa and Asia. Despite its importance in the etiology of the disease, the molecular mechanisms involved in the interaction of F. pedrosoi with the host are still poorly explored. During the infectious process, the host limits the availability of zinc to fungal pathogens in order to contain the infection, a process called nutritional immunity. In this work, we show that F. pedrosoi is able to grow in a wide range of zinc concentration and that genes related to zinc uptake are induced in zinc-limiting conditions. Proteomic analysis revealed that after 48 h of exposure to zinc scarcity synthesis of fatty acid and the pentose-phosphate pathway are up-regulated. On the other hand, protein synthesis is repressed. Additionally, glucan increases while chitin content is reduced in the cell wall under zinc limitation, demonstrating that cell wall remodeling is important for adaptation to this stress condition.
Project description:Mosquito-borne helminth infections are responsible for a significant worldwide disease burden in both humans and animals. Accordingly, development of novel strategies to reduce disease transmission by targeting these pathogens in the vector are of paramount importance. We found that a strain of Aedes aegypti that is refractory to infection by Dirofilaria immitis, the agent of canine heartworm disease, mounts a stronger immune response during infection than does a susceptible strain. Moreover, activation of the Toll immune signaling pathway in the susceptible strain arrests larval development of the parasite, thereby decreasing the number of transmissionstage larvae. Notably, this strategy also blocks transmission stage Brugia malayi, an agent of human lymphatic filariasis. Our data show that mosquito immunity can play a pivotal role in restricting filarial nematode development and suggest that genetically engineering mosquitoes with enhanced immunity will help reduce disease transmission.
Project description:It has been reported that Cryptosporidium parvum, a species of a protozoan frequently isolated from humans and animals, is able to induce digestive adenocarcinoma in a rodent model. Consistently, some epidemiological studies have reported an association with cryptosporidiosis in patients with colorectal adenocarcinoma. However, the correlation between cryptosporidiosis and human digestive cancer remains unclear at this time, and it is not known whether this intracellular parasite, considered an opportunistic agent, is able to induce gastrointestinal malignancies in humans. In order to add new arguments for a probable association between cryptosporidiosis and digestive human cancer, the main aim of this study is to determine prevalence and to identify species of Cryptosporidium among a French digestive cancer population.