Some like it hot, some like it cold; Proteome comparison of Leptospira borgpetersenii serovar Hardjo strains propagated at different temperatures

Authors: Putz, Ellie; FERNANDES, L.G.V. - Butantan Institute; SIVASANKARAN, S. - Iowa State University; Bayles, Darrell; Alt, David; Lippolis, John; Nally, Jarlath

Submitted to: Journal of Proteomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/29/2022
Publication Date: 5/6/2022
Citation: Putz, E.J., Fernandes, L., Sivasankaran, S., Bayles, D.O., Alt, D.P., Lippolis, J.D., Nally, J.E. 2022. Some like it hot, some like it cold; Proteome comparison of Leptospira borgpetersenii serovar Hardjo strains propagated at different temperatures. Journal of Proteomics. 262(2022). Article 104602. https://doi.org/10.1016/j.jprot.2022.104602.
DOI: https://doi.org/10.1016/j.jprot.2022.104602

Interpretive Summary: Leptospirosis is a zoonotic disease caused by the spirochete bacteria of the genus Leptospira affecting humans and all major livestock species. Cattle act as a reservoir host for L. borgpetersenii serovar Hardjo which colonize the kidneys and reproductive tract from which they are excreted and transmitted to other cattle via urine, semen or uterine discharges. Bovine leptospirosis results in reproductive failure, abortion, stillbirth and loss of milk production, and is an occupational risk for those working with infected animals. Though vaccines exist, they lack cross protection across serogroups, and instead rely on inclusion of multiple carefully selected serovars from laboratory strains prepared at 29°C. Recent interest in variation at the Leptospira strain level, along with a newly achieved culture temperature of 37°C (which more closely resembles host body temperature), led us to investigate the proteomic profiles of an older, established challenge strain HB203 compared to newly isolated TC129 and TC273 strains isolated from abattoir cattle in the central United States. Herein, we identify substantial proteomic differences not only between strains of the same species and serovar, but notably within strains between growth temperatures. Collectively this work suggests that bacterin vaccine composition may benefit from investigating strain selection and temperature of preparation.

Technical Abstract: Leptospirosis is a global zoonotic disease affecting most mammals including humans, companion animals, and all major livestock species. A unique level of species specificity exists between host and pathogen where susceptibility and severity of disease presentation are partly determined by unique interactions between incidental or reservoir animal host species and the species, serovar, and strain of Leptospira. While bacterin vaccines for leptospirosis exist, they suffer from a lack of cross protection between serogroups, and instead focus on multiple serovar inclusion utilizing laboratory strains propagated at 29°C. Recent work has shown substantial variation in the transcriptome between strains of identical species and serovar of Leptospira. In this work, substantial differences in protein abundance profiles were identified between different strains of Leptospira borgpetersenii serovar Hardjo; a previously well-established strain designated HB203 that was isolated in the late 1980s, and newer strains designated TC129 and TC273 isolated in 2016. Notably, proteomic expression patterns also identified differences within strains propagated at the routine temperature of 29°C, compared to the newly achieved culture temperature of 37°C which more closely emulates conditions encountered during host infection. While 388 and 385 significantly differentially expressed (DE) proteins (FDR of 0.01) were identified in HB203 versus TC129, and HB203 versus TC273 when propagated at 29°C respectively, only 66 and 4 DE proteins were identified in HB203 versus TC129, and HB203 versus TC273 when propagated at 37°C respectively. Within each strain comparing temperatures, HB203 had 524 significantly DE proteins, TC129 had 347 DE proteins, and TC273 had 569 DE proteins. Our results highlight significant differential protein expression, including virulence factors, amongst identical serovars of L. borgpetersenii propagated at 29oC, the collective variation of which can be diminished when propagated at 37oC. Collectively, there is increasingly more evidence available to suggest bacterin vaccine design would benefit from consideration of strains employed and potential effects of growth temperature related to specific behavior of pathogens in vaccine composition.