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Ecological specialization and constrained evolution shape virulence diversity in zoonotic pathogen L. interrogans

ABSTRACT: Host specialization is central to the emergence of zoonotic pathogens, yet mechanisms shaping bacterial adaptation across diverse hosts remain poorly understood. Leptospira interrogans circulates among an exceptionally broad range of reservoirs, but only serogroup Icterohaemorrhagiae dominates the global burden of human leptospirosis, raising fundamental questions about its ecological and pathogenic success. Here, we integrate a global genomic dataset to dissect host adaptation in L. interrogans. Population genomic analyses reveal that serogroups Icterohaemorrhagiae and Pomona dominate worldwide and display signatures of ecological specialization. These serogroups have followed distinct evolutionary trajectories that are central to host specialization, characterized by extensive divergence in membrane and signaling genes, together with the acquisition of specialized functional repertoires linked to host adaptation. Transcriptomic and proteomic profiling demonstrate that these genomic differences are coupled to distinct regulatory programs, predominantly affecting virulence and stress response. Altogether, these findings demonstrate that intraspecies heterogeneity in L. interrogans emerges from the convergence of genomic constraint, membrane remodeling and regulatory divergence, shaping host specialization and zoonotic pathogenicity.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE330072 | GEO | 2026/06/25

REPOSITORIES: GEO

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	GSE330072_Human_raw_counts.txt.gz	Txt
	GSE330072_Murine_raw_counts.txt.gz	Txt

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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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Ecological specialization and constrained evolution shape virulence diversity in zoonotic pathogen L. interrogans

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