Leptospira: Invasion, Pathogenesis and Persistence

Faisal, Syed M.; McDonough, Sean P.; Chang, Yung-Fu

doi:10.1007/978-1-4614-5404-5_8

Cited by 12 publications

(13 citation statements)

References 161 publications

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“…The most common global bacterial zoonosis, leptospirosis, is an active target of recombinant vaccine development (Picardeau, ). Over one million severe cases of human leptospirosis are estimated to occur each year resulting in approximately 60,000 deaths (Costa et al, ; Faisal, McDonough, & Chang, ). Existing commercial vaccines rely on inactivated or fragmented Leptospira spp.…”

Section: Introductionmentioning

confidence: 99%

Comparative screening of recombinant antigen thermostability for improved leptospirosis vaccine design

Ptak

Akif

Hsieh

et al. 2018

Biotech & Bioengineering

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Recombinant antigens exhibit targeted protectiveproperties and offer important opportunities in the development of therapeutic technologies. Biophysical and structural methods have become important tools for the rational design and engineering of improved antigen-based vaccines. Vaccines containing Leptospira immunoglobulin-like (Lig) protein-derived antigens are currently the most promising candidates for protective immunity against the globally prevalent bacterial pathogen, Leptospira interrogans; however, vaccine trials using these domains have produced inconsistent results. Here, we compare the thermostability of domains from the main immunogenic regions from major leptospiral antigens, LigA and LigB. By measuring temperature-dependent fluorescence decay of the hydrophobic core tryptophan, 17 individual Lig protein immunoglobulin-like (Ig-like) domains were shown to display a broad range of unfolding temperatures. For a majority of the domains, stability issues begin to occur at physiologically relevant temperatures. A set of chimeric Ig-like domains was used to establish the ability of transplanted domain regions to enhance thermostability. Further insights into the determinants for domain stabilization were explored with nuclear magnetic resonance dynamics and mutational analysis. The current study has yielded a set of thermostable Ig-like domain scaffolds for use in engineering antigen-based vaccines and demonstrates the importance of incorporating thermostability screening as a design parameter.

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Section: Introductionmentioning

confidence: 99%

Comparative screening of recombinant antigen thermostability for improved leptospirosis vaccine design

Ptak

Akif

Hsieh

et al. 2018

Biotech & Bioengineering

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“…Pathogenic Leptospira spp. cause leptospirosis a zoonotic disease that is prevalent in people, dogs, pigs, horses, cattle, sheep, goats and wild animals [1,2]. The disease occurs widely in developing countries, such as Thailand, Brazil and India, and is reemerging in developed countries [3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…Although the incidence of human leptospirosis in the United States is relatively low, disease incidence in domestic animals has increased in recent years [3]. Leptospiral infection can range in severity from an inapparent infection to death from pulmonary hemorrhage, renal disease or hepatic failure [1,2,8,9]. Leptospiral infection can also cause uveitis and is considered the leading cause of blindness in horses [10,11].…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of Leptospira interrogans Outer Membrane Vesicles in a Hamster Model

Kunjantarachot¹,

Yan²,

McDonough³

et al. 2014

J Vaccines Vaccin

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Animal Leptospirosis, caused by Leptospira spp., is one of the most common zoonotic diseases in the US and throughout the world. Commercially available bacterins are only partially efficacious in that they protect against death, but not against disease. Protective immunity to Leptospira spp. require antibodies specific to outer surface proteins and/or adhesins of leptospires. Spirochetes produce membrane blebs or vesicles (OMVs) and OMVs have been shown to be good immunogens. In this study, we characterized leptospiral OMV components by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of and identified that the majority (58.1%) of proteins in the vesicles were cytoplasmic proteins (294 of 506), while 5 were extracellular proteins (0.99%), 11 were outer membrane proteins (2.17%), 14 were periplasmic proteins (2.77%), 48 were cytoplasmic/inner membrane proteins (9.49%) and 134 were unknown or having multiple locations (26.48%). Transmission electron microscopy (TEM) imaging showed OMVs are spherical bodies with a diameter of 50-200 nm. Vesicles were used to vaccinate hamsters. The results indicated that immunization with Leptospira OMVs induced significant protection against lethal challenge revealed by an enhanced humoral immune response, high survival rate and significantly reduced bacterial burden, all of which were reflected in decreased pulmonary, hepatic and renal lesions (p<0.05). To the best of our knowledge, this is the first report showing that OMVs could be used as a novel vaccine formulation to protect hamsters against lethal challenge.

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“…Leptospira organisms are able attach and invade a range of host cells, including epithelial cells, by a number of surface-exposed proteins or secretory proteins causing pore formation in the cell (Faisal et al, 2012). These organisms only transiently reside within these cells as they translocate (Faisal et al, 2012).…”

Section: Bacterialmentioning

confidence: 99%

“…These organisms only transiently reside within these cells as they translocate (Faisal et al, 2012).…”

Section: Bacterialmentioning

confidence: 99%

Pathology of equine amnionitis and foetal lLoss: clinical and experimental studies

Todhunter¹

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Detailed experience in identifying the appearance of setal fragments which is highlighted under toluidine blue staining allowed in depth examination of tissues from equine abortions submitted for examination in 2012. Five cases were found in which a caterpillar setal fragment was found in the allantochorion confirming that setal fragments migrate from field exposure as well as experimental exposure to processionary caterpillars.The experiments in this thesis have shown histologically for the first time, the ability of Processionary caterpillar setae to penetrate the maternal gut wall and migrate directly into the uterus and placental tissues. This is considered to be the most likely means of translocation of bacteria to the foetal membranes. The direct, rapid migration of setae in as little as two days from ingestion from the gut to the placenta facilitates bacterial infection.Bacteria present in the mare's gut likely attach to migrating setal fragments and translocate through the gut wall, the uterus and the foetal membranes in which they subsequently colonize. Incomplete migration of setal fragments may account for the focal mucoid placentitis induced when mares were exposed in early gestation. Bacterial colonization of 5 the foetal membranes and/or foetus may cause foetal compromise or death and eventual abortion.The variety of manifestations of EAFL due to the migration of setal fragments ranging from acute abortion, chronic active placentitis, stillbirth, compromised preterm and full term foals, and focal mucoid placentitis have a significant impact on the breeding of horses and ultimately the racing industry in Australia.6

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Leptospira: Invasion, Pathogenesis and Persistence

Cited by 12 publications

References 161 publications

Comparative screening of recombinant antigen thermostability for improved leptospirosis vaccine design

Comparative screening of recombinant antigen thermostability for improved leptospirosis vaccine design

Immunogenicity of Leptospira interrogans Outer Membrane Vesicles in a Hamster Model

Pathology of equine amnionitis and foetal lLoss: clinical and experimental studies

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