Project description:Leptospirosis is a neglected zoonotic disease of global importance. Despite its prevalence, pathogenesis is still poorly understood. Our aim was to discover transcripts responsable for pathogenicity of leptospirosis. We compared the transcriptome profiles of saprophyte, attenuated and virulent strain of Leptospira spp.
Project description:Leptospirosis is a globally important infectious disease caused by an infection with pathogenic Leptospira spp. and associated with kidney injury due to sustained tubulointerstitial inflammation. We apply the high-throughput Illumina sequencing platforms to determine the murine renal transcriptome and investigate gene expression alterations and biological pathways associated with kidney damage induced by leptospiral infection. The goal of this study is to investigate a global analysis of renal gene expression associated with renal damage that was induced by leptospiral infection in experimental mice models.
Project description:Pathogenic Leptospira spp. are the causative agents of the zoonotic disease leptospirosis. During infection, Leptospira are confronted with deadly reactive oxygen species (ROS). Withstanding ROS produced by the host innate immunity is an important strategy evolved by pathogenic Leptospira for persisting in and colonizing hosts. The peroxide stress regulator, PerR, represses genes involved in ROS defenses in L. interrogans. We have performed RNA sequencing in WT and perR mutant strains to characterize the L. interrogans adaptive response to hydrogen peroxide. We showed that Leptospira solicit three main peroxidase machineries (catalase, cytochrome C peroxidase and peroxiredoxin) and heme to adapt to peroxide stress as well as canonical chaperones of the heat shock response, and DNA repair. Determining the PerR regulon allowed to identify the PerR-dependent mechanisms of the peroxide adaptive response and has revealed a regulatory network involving other transcriptional regulators, two-component systems and sigma factors as well as non-coding RNAs that putatively orchestrate, in concert with PerR, this adaptive response. Our findings provide comprehensive insight into the mechanisms required by pathogenic Leptospira to overcome infection-related oxidants. This will participate in framing future hypothesis-driven studies to identify and decipher novel virulence mechanisms.
Project description:Leptospirosis caused by pathogenic Leptospira spp. leads to kidney damage that may progress to chronic kidney disease. However, how leptospiral infections lead to renal damage is unclear. Here, we apply microarray platforms to determine the murine renal transcriptome-wide investigation of gene expression changes and biological pathways associated with leptospiral infection-related kidney damage. The aims of this study are to investigate a global analysis of renal gene expression associated with renal damage that was induced by leptospiral infection using experimental murine models. The result of microarray analysis showed that 467 and 927 genes to be differentially expressed in mice kidney with pathogenic leptospiral infection after day 7 and 28, respectively. Moreover, the result also showed that the 508 significantly differentially expressed genes in the kidneys of mice after infection with non-pathogenic leptospires at 7 days post-infection, and the 1,067 transcripts significantly differentially expressed in these kidneys at 28 days post-infection. Biological pathways performed using KEGG pathway enrichment analysis (P-value < 1E-5) showed that a total of 6 and 7 pathways were significantly enriched at 7 and 28 days post-infection with pathogenic leptospires, respectively. A total of 25 pathways were significantly enriched at day 28 following the non-pathogenic leptospiral infection. However, none of pathways were found in microarray data at day 7 post-infection with non-pathogenic leptospires. In addition, the antigen processing and presentation pathways was significantly enriched at 7 and 28 days post-infection with pathogenic leptospires, and at day 28 following the non-pathogenic leptospiral infection.
Project description:There has been a significant increase in the number of reported human cryptosporidiosis cases in recent years. The aim of this study is to estimate the prevalence of Cryptosporidium spp. in wild rodents and shrews, and investigate the species and genotype distribution to assess zoonotic risk. Partial 18S rRNA gene nested-PCR reveals that 36.8, 53.9 and 41.9% of mice, voles and shrews are infected with Cryptosporidium species. The highest prevalence occurred in the Microtus agrestis (field vole) and Myodes glareolus (bank vole). Interestingly, bank voles caught in fields were significantly more often Cryptosporidium-positive compared to those caught in forests. The proportion of infected animals increases from over-wintered (spring and summer) to juveniles (autumn) suggesting acquired immunity in older animals. Based on Sanger sequencing and phylogenetic analyses, Apodemus flavicollis (yellow-necked mouse) is commonly infected with zoonotic C. ditrichi. Voles carry multiple different Cryptosporidium sp. and genotypes, some of which are novel. C. andersoni, another zoonotic species, is identified in the Craseomys rufocanus (grey-sided vole). Shrews carry novel shrew genotypes. In conclusion, this study indicates that Cryptosporidium protozoan are present in mouse, vole and shrew populations around Finland and the highest zoonotic risk is associated with C. ditrichi in Apodemus flavicollis and C. andersoni in Craseomys rufocanus. C. parvum, the most common zoonotic species in human infections, was not detected.
Project description:Pathogenic Leptospira spp. are the causative agents of the zoonotic disease leptospirosis. During infection, Leptospira are confronted with deadly reactive oxygen species (ROS). Withstanding ROS produced by the host innate immunity is an important strategy evolved by pathogenic Leptospira for persisting in and colonizing hosts. The peroxide stress regulator, PerRA, represses genes involved in ROS defenses in L. interrogans. We have identified an ORF encoding a putative second PerR in pathogenic Leptospira that we named PerRB. We have determined the transcriptomic profil of a single perRB and a double perRAperRB mutants. The concomitant inactivation of perRA and perRB has a pleiotropic effect on the transcriptomic profil of L. interrogans. The lack of both PerRA and PerRB regulators led to the differential expression of several virulence-associated genes and a loss of virulence. Our findings provide new insights into a new regulatory network that controls virulence and host colonization.
Project description:Leptospirosis is a re-emerging zoonosis, a globally important infectious disease, caused by an infection with the genus Leptospira. Leptospirosis is associated with acute kidney injury and progress to CKD due to sustained tubulointerstitial inflammation. Macrophages play a critical role in controlling the bacterial burden and tissue inflammation during the spirochete infections. To understand the molecular mechanisms of leptospia-induced macrophage activation and its role in the inflammatory process, we performed the transcriptome profiles of murine bone marrow-derived macrophages infected with pathogenic and non-pathogenuc Leptospira spp.at a multiplicity of infection of 100 for 2 and 24 hrs, respectively.