Project description:Zoonotic pathogens account for the majority of emerging and re-emerging infectious diseases, yet the evolutionary mechanisms underlying their host specialization remain largely unexplained. Here, by combining comparative genomics and transcriptomics and the response of macrophages of varying hosts, we investigated the adaptive host evolution in the Bacterial celll zoonotic pathogen model Leptospira interrogans. Genomic analyses reveal that specialized genogroups exhibit specific signatures, characterized by reduced nucleotide diversity and restricted pangenome openness. We identify adaptive hotspots in genes encoding virulence factors, membrane proteins and environmental sensors, suggesting that positive selection in these genes is likely the primary drivers behing the emergence of genogroups. Focusing on the predominant genogroups associated with serogroups Icterohaemorrhagiae and Pomona, we uncover unique protein domain acquisitions linked to host adaptation, as well as a genogroup-specific gene expression programs potentially affecting virulence, secretion systems and metabolic pathways. Finally, infection of macrophages of different hosts elicits distinct immune responses, further validating ecological specialization of certain genogroups. Together, our findings suggest that intraspecies heterogeneity in L. interrogans is driven by niche specialization through differences in gene content, mutation rate variation and regulation of transcriptional programs.

2026-06-25 | GSE311287 | GEO

Analysis of the human endothelial cell response to pathogenic Leptospira interrogans vs. non-pathogenic Leptospira biflexa (HMEC data)

Project description:The overall goal of these experiments was to determine how human endothelial cells respond to pathogenic Leptospira interrogans. Leptospira interrogans causes leptospirosis, the most widespread zoonotic infection in the world. A hallmark of leptospirosis is widespread endothelial damage, which in severe cases leads to hemorrhage. In these experiments, we infected two endothelial cell lines with pathogenic Leptospira interrogans serovar Canicola strain Ca12-005, and as controls, with the non-pathogenic Leptospira biflexa serovar Patoc strain Pfra. As additional controls, uninfected cells were also included in the analyses. The cell line used fhere was a microvascular endothelial line, HMEC (Ades et al, 1992. HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J Invest Dermatol. 99:683-690); due to loss of the original analysis files, only raw data files are provided. Infection times were performed at a multiplicity of infection (# bacteria/endothelial cell) of 10 for either 1 hour or 3 hours, after which RNA was harvested and reverse transcribed. Labeled cDNAs were used to probe HEEBO arrays purchased from Microarrays Inc. (Nashville, TN). In each of three biological replicate experiments, for each time point, three comparisons were made. First, the L. interrogans-infected cells were compared to the L. biflexa-infected cells. Second, the L. Interrogans-infected cells were compared to the uninfected cells. Third, the L. biflexa-infected cells were compared to the uninfected cells. A second endothelial cell line,

2010-07-27 | E-GEOD-23173 | biostudies-arrayexpress

Leptospira interrogans serovar Pomona str. Kennewicki LC82-25

Project description:Leptospira interrogans serovar Pomona str. Kennewicki LC82-25 Genome sequencing and assembly

| PRJNA74051 | ENA

Analysis of the human endothelial cell response to pathogenic Leptospira interrogans vs. non-pathogenic Leptospira biflexa (Eahy1 data)

Project description:The overall goal of these experiments was to determine how human endothelial cells respond to pathogenic Leptospira interrogans. Leptospira interrogans causes leptospirosis, the most widespread zoonotic infection in the world. A hallmark of leptospirosis is widespread endothelial damage, which in severe cases leads to hemorrhage. In these experiments, we infected two endothelial cell lines with pathogenic Leptospira interrogans serovar Canicola strain Ca12-005, and as controls, with the non-pathogenic Leptospira biflexa serovar Patoc strain Pfra. As additional controls, uninfected cells were also included in the analyses. The cell line used was Ea.hy926, a macrovascular line (Edgell, C. J.,et al. 1990. In vitro Cell. & Dev. Biol. 26:1167-1172, and Edgell, C. J., et al. 1983. Proc. Natl. Acad. Sci. 80:3734-3737). Infection times were performed at a multiplicity of infection (# bacteria/endothelial cell) of 10 for either 1 hour or 3 hours, after which RNA was harvested and reverse transcribed. Labeled cDNAs were used to probe HEEBO arrays purchased from Microarrays Inc. (Nashville, TN). In each of three biological replicate experiments, for each time point, three comparisons were made. First, the L. interrogans-infected cells were compared to the L. biflexa-infected cells. Second, the L. Interrogans-infected cells were compared to the uninfected cells. Third, the L. biflexa-infected cells were compared to the uninfected cells. A second endothelial cell line, HMEC (Ades et al, 1992. HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J Invest Dermatol. 99:683-690), which is of microvascular origin, was also used; raw data files are provided separately.

2010-07-27 | E-GEOD-23172 | biostudies-arrayexpress

Global transcriptomic response of Leptospira interrogans serovar Copenhageni upon exposure to serum

Project description:L. interrogans, a causative agent of leptospirosis, can survive in the environment for lengthy periods of time in between infection of mammalian hosts. In order to identify genes involved in survival in the early spirochetemic phase of infection, we performed a transcriptional analysis of L. interrogans serovar Copenhageni upon exposure to serum in comparison with EMJH medium.

2010-03-31 | GSE17942 | GEO

Leptospira interrogans serovar australis

Project description:Leptospira interrogans serovar Australis genome sequencing

| PRJNA62115 | ENA