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Early Transcriptomic Response of Leptospira interrogans in an Ovine Dialysis Membrane Chamber Model

ABSTRACT: Leptospirosis is a major zoonotic disease affecting both public health and livestock production. In ruminants, serovar Hardjo is of particular importance because of its ability to establish persistent infections, whereas serogroup Icterohaemorrhagiae is generally associated with incidental infection. The molecular basis of adaptation of serovar Hardjo to the ruminant host remain poorly understood. . The dialysis membrane chamber (DMC) model enables investigation of the short-term transcriptional response of leptospires to the host environment, including nutrient limitation, temperature and osmotic shifts, and soluble host-derived factors. In this study, an ovine peritoneal DMC model was used to compare the transcriptional responses of L. interrogans serovar Hardjo strains KR40 and N116 with those of L. interrogans serogroup Icterohaemorrhagiae strains KR93 and KR95. For each strain, transcriptomic data were obtained after 24 h and 72 h of incubation in DMCs, as well as from in vitro cultures grown in T80/40/LH medium. This experimental design enabled the identification of shared and strain-associated transcriptional responses to the host environment.

ORGANISM(S): Leptospira interrogans

PROVIDER: GSE342756 | GEO | 2026/08/16

REPOSITORIES: GEO

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Project description:Leptospirosis, an emerging zoonotic disease with worldwide distribution, is caused by spirochetes belonging to the genus Leptospira. More than 500,000 cases of severe leptospirosis are reported annually, with .10% of these being fatal. Leptospires can survive for weeks in suitably moist conditions before encountering a new host. Reservoir hosts, typically rodents, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. In humans, leptospires can cause a variety of clinical manifestations, ranging from asymptomatic or mild fever to severe icteric (Weil’s) disease and pulmonary haemorrhage. Currently, little is known about how Leptospira persist within a reservoir host. Prior in vitro studies have suggested that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. However, no study has examined gene expression by leptospires within a mammalian host-adapted state. To obtain a more faithful representation of how leptospires respond to host-derived signals, we used RNA-Seq to compare the transcriptome of L. interrogans cultivated within dialysis membrane chambers (DMCs) implanted into the peritoneal cavities of rats with that of organisms grown in vitro. In addition to determining the relative expression levels of ‘‘core’’ housekeeping genes under both growth conditions, we identified 166 genes that are differentially-expressed by L. interrogans in vivo. Our analyses highlight physiological aspects of host adaptation by leptospires relating to heme uptake and utilization. We also identified 11 novel non-coding transcripts that are candidate small regulatory RNAs. The DMC model provides a facile system for studying the transcriptional and antigenic changes associated with mammalian host-adaption, selection of targets for mutagenesis, and the identification of previously unrecognized virulence determinants. Transcriptome analysis of L. interrogans Copenhageni FIOCRUZ L1-130 using RNA from 2 different conditions using RNA-seq. Also, the reproducibility and robustness of data is ensured by three biological replicates from each condition.

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Early Transcriptomic Response of Leptospira interrogans in an Ovine Dialysis Membrane Chamber Model

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