Dataset Information

Pathogenic Leptospires Modulate Protein Expression and Post-translational Modifications in Response to Mammalian Host Signals.

ABSTRACT: Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Reservoir hosts of leptospirosis, including rodents, dogs, and cattle, 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. Whilst little is known about how Leptospira adapt to and persist within a reservoir host, in vitro studies suggest that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. We applied the dialysis membrane chamber (DMC) peritoneal implant model to compare the whole cell proteome of in vivo derived leptospires with that of leptospires cultivated in vitro at 30°C and 37°C by 2-dimensional difference in-gel electrophoresis (2-D DIGE). Of 1,735 protein spots aligned across 9 2-D DIGE gels, 202 protein spots were differentially expressed (p < 0.05, fold change >1.25 or < -1.25) across all three conditions. Differentially expressed proteins were excised for identification by mass spectrometry. Data are available via ProteomeXchange with identifier PXD006995. The greatest differences were detected when DMC-cultivated leptospires were compared with IV30- or IV37-cultivated leptospires, including the increased expression of multiple isoforms of Loa22, a known virulence factor. Unexpectedly, 20 protein isoforms of LipL32 and 7 isoforms of LipL41 were uniformly identified by DIGE as differentially expressed, suggesting that unique post-translational modifications (PTMs) are operative in response to mammalian host conditions. To test this hypothesis, a rat model of persistent renal colonization was used to isolate leptospires directly from the urine of experimentally infected rats. Comparison of urinary derived leptospires to IV30 leptospires by 2-D immunoblotting confirmed that modification of proteins with trimethyllysine and acetyllysine occurs to a different degree in response to mammalian host signals encountered during persistent renal colonization. These results provide novel insights into differential protein and PTMs present in response to mammalian host signals which can be used to further define the unique equilibrium that exists between pathogenic leptospires and their reservoir host of infection.

SUBMITTER: Nally JE

PROVIDER: S-EPMC5553009 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Pathogenic Leptospires Modulate Protein Expression and Post-translational Modifications in Response to Mammalian Host Signals.

Nally Jarlath E JE Grassmann Andre A AA Planchon Sébastien S Sergeant Kjell K Renaut Jenny J Seshu Janakiram J McBride Alan J AJ Caimano Melissa J MJ

Frontiers in cellular and infection microbiology 20170809

Pathogenic species of <i>Leptospira</i> cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Reservoir hosts of leptospirosis, including rodents, dogs, and cattle, 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. Whilst little is known about how <i>Leptospir ...[more]

PMID: 28848720

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Project description:A large body of work has demonstrated that leptospires regulate and modify gene expression in response to environmental cues, as encountered during disease transmission, including changes in temperature, osmolarity, concentration of iron, the presence of serum, and interaction with macrophages. However, since leptospires are not readily amenable to genetic manipulation, the functional and biological significance of these differentially expressed genes often remains unclear. More recently, it is been shown that proteins, in response to changing environmental conditions, can be modified further by specific post-translational modifications. Indeed, both saprophytic and pathogenic leptospires have comprehensive systems to modify proteins. The paucibacillary nature of spirochetal infections, combined with the challenges associated with acquiring pathogens free from contaminating host proteins makes the study of these bacteria in a mammalian host-adapted state inherently difficult. As an alternative approach, we developed a model in which leptospires are cultivated in a dialysis membrane chamber (DMC) implanted within the peritoneal cavity of rats, where they are exposed to the environmental cues encountered during host infection. This strategy has been successfully applied to compare the transcriptome of L. interrogans cultivated within DMC with that of leptospires grown under standard in vitro conditions. In addition to determining the relative expression levels of ‘‘core’’ housekeeping genes under both growth conditions, we identified 166 genes that were differentially-expressed by L. interrogans in response to mammalian host signals. The proteome of DMC (dialysis membrane chamber) cultivated leptospires was compared to that of in vivo derived leptospires and with leptospires cultivated in vitro at 30°C or 37°C by 2-dimensional difference in gel electrophoresis (2-D DIGE). Our analysis indicates that the abundance of leptospire-proteins is modulated the expression of a range of proteins which are differentially expressed in response to mammalian host signals, and not temperature alone . In addition, we confirm that in several proteins there is a change in the presence of modify the expression of the post-translational modifications trimethyllysine and acetyllysine in response to environmental cues encountered during persistent renal colonization in a reservoir host of infection. These results provide novel insights in the proteome level changes, including to differential protein and post-translational modifications, expressed in response to mammalian host signals which can be used to further define the unique equilibrium that exists between pathogenic leptospires and their reservoir host of infection.

Dataset Information

Pathogenic Leptospires Modulate Protein Expression and Post-translational Modifications in Response to Mammalian Host Signals.

Publications

Pathogenic Leptospires Modulate Protein Expression and Post-translational Modifications in Response to Mammalian Host Signals.

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