Failure of a heterologous recombinant Sca5/OmpB protein based vaccine to elicit effective protective immunity against<i>Rickettsia rickettsii</i>infections in C3H/HeN mice

Riley, Sean P.; Cardwell, Marissa M.; Chan, Yvonne G. Y.; Pruneau, Ludovic; Piero, Fábio Del; Martínez, Juan José

doi:10.1093/femspd/ftv101

Cited by 18 publications

(29 citation statements)

References 16 publications

(26 reference statements)

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“…” Similarly, total RNA was isolated from liver tissues of C3H/HeN mice at five days post infection with 1x10 7 intravenous R . rickettsii [ 11 ]. These mice were moribund and were euthanized prior to succumbing to R .…”

Section: Methodsmentioning

confidence: 99%

“…DNA was removed from the RNA purification using Ambion Turbo DNAse according to manufacturer’s instructions. Removal of DNA contamination was verified by sca1 PCR as previously described [ 11 ]. Quality control was performed on a Fragment Analyzer (Advanced Analytical) to determine the RNA quality number (RQN).…”

Section: Methodsmentioning

confidence: 99%

“…rickettsii transcriptome within the infected mammal; therefore, we chose to analyze R . rickettsii within the liver of moribund C3H/HeN mice, because this sample contains multiple infected host cells types with the largest rickettsial load currently established [ 11 ]. The highest ratio of R .…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of changes to the Rickettsia rickettsii transcriptome during mammalian infection

Riley¹,

Pruneau²,

Martínez³

2017

PLoS ONE

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The lifecycle of Rickettsia rickettsii includes infection of both mammalian and arthropod hosts, with each environment presenting distinct challenges to survival. As such, these pathogens likely have distinctive transcriptional strategies for infection of each host. Herein, we report the utilization of next generation sequencing (RNAseq) and bioinformatic analysis techniques to examine the global transcriptional profile of R. rickettsii within an infected animal, and to compare that data to transcription in tissue culture. The results demonstrate substantial R. rickettsii transcriptional alteration in vivo, such that the bacteria are considerably altered from cell culture. Identification of significant transcriptional changes and validation of RNAseq by quantitative PCR are described with particular emphasis on known antigens and suspected virulence factors. Together, these results suggest that transcriptional regulation of a distinct cohort of genes may contribute to successful mammalian infection.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Evaluation of changes to the Rickettsia rickettsii transcriptome during mammalian infection

Riley¹,

Pruneau²,

Martínez³

2017

PLoS ONE

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“…Dzul-Rosado y cols. 2017 (41) disminuyó la letalidad en un 100% en ratones infectados (17,24). Desde hace algunos años, se estudian como alternativa las vacunas de ADN, las cuales son desarrolladas mediante la expresión de péptidos específicos por medio de plásmidos, entre los cuales, diversos fragmentos de OmpA y OmpB han sido capaces de inducir proliferación en los linfocitos T, junto a la producción de citoquinas en macrófagos que han sido co-cultivados con linfocitos humanos.…”

Section: Crocquetunclassified

“…Hasta el momento, se han evaluado proteínas implicadas en la invasión celular (InvA), proteínas de secreción (Fts), Adr2, Sca5, YbgF y TolC (14)(15)(16). Sin embargo las más estudiadas son las proteínas transmembranales OmpA y OmpB, debido a su alta antigenicidad y su importante papel en el mecanismo de patogenicidad de las bacterias del género Rickettsia (12,17,18).…”

Section: Introductionunclassified

Importancia de las proteínas OmpA y OmpB en el desarrollo de vacunas contra la rickettsiosis

Martinez-Miranda¹,

Balam-Romero²,

Dzul-Rosado³

2019

Rev Biomed

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Las Rickettsiosis son un grupo de enfermedades zoonóticas causadas por las bacterias del género Rickettsia. Transmitidas por vectores ectoparásitos hematófagos como garrapatas, piojos, pulgas y ácaros, cuya incidencia ha aumentado en los últimos años. Debido a su cuadro clínico inespecífico es subdiagnosticada y confundida con otras de mayor influencia. Debido a su creciente incidencia se han estudiado antígenos rickettsiales, asi como la respuesta inmune que generan, para poder desarrollar una vacuna que permita combatir el número de casos de rickettsiosis. De estos estudios se han identificado diversas proteínas de membrana como candidatas para la realización de vacunas, siendo OmpA y la OmpB las más destacadas. Recientes estudios destacan una respuesta inmune efectiva contra esta enfermedad por lo que la presente revisión tiene como objetivo brindar un panorama de los resultados obtenidos en estudios de vacunas generadas a partir de estas dos proteínas.

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Rickettsia

Fournier¹,

Raoult²

2019

Bergey's Manual of Systematics of Archaea and Bacteria

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Rick.ett'si.a. N.L. fem. n. Rickettsia, named after Howard Taylor Ricketts, who first associated these microorganisms with spotted fever and typhus and who died of typhus contracted in the course of his studies. Proteobacteria / Alphaproteobacteria / Rickettsiales / Rickettsiaceae / Rickettsia Short , often paired rods , 0 . 3–0 . 5 μ m × 0 . 8–2 . 0 μ m . The rickettsial envelope has a typical Gram‐negative structure with a bilayer inner membrane, a peptidoglycan layer, and a bilayer outer membrane. The cells are often surrounded by a protein microcapsular layer and slime layer. Rickettsiae retain basic fuchsin when stained by Giménez method. The organisms are obligately intracellular and reside free in the cytoplasm of eukaryotic host cells , where they divide by binary fission . Rickettsiae of the spotted fever group (SFG) may also reside in the nucleus of eukaryotic host cells. Rickettsiae are closely associated with arthropods (ticks, mites, fleas, lice, and other insects) for their maintenance in nature . Their natural cycle usually involves both a vertebrate and an invertebrate host. For some, the arthropod host is both a reservoir and a vector. Transovarian transmission of the agent from the infected female to the next generation is the essential mechanism for the maintenance of many species. Rickettsial cells are usually unstable when separated from host components, except for highly stable forms found in the feces of arthropod hosts; stability can be enhanced by certain proteins, sucrose, and reagents that tend to maintain the integrity of outer membranes, osmolarity, and ATP level. Rickettsiae are best preserved by rapid freezing and storage below −50°C. The cells are rapidly inactivated at 56°C. Rickettsiae derive energy from the metabolism of glutamate via the citric acid cycle, but do not utilize glucose. They transport and metabolize phosphorylated compounds but do not synthesize or degrade nucleoside monophosphates. Rickettsial species have genomes ranging from 1.1 to 2.3 Mb. They may also have up to four plasmids. Rickettsiae are etiological agents of typhus and spotted fevers in humans . There are 31 recognized species. DNA G + C content (mol%) : 29–33. Type species : Rickettsia prowazekii da Rocha‐Lima 1916, 567. (Nom. Cons. Opin. 19, Jud. Comm. 1958, 158.)

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Failure of a heterologous recombinant Sca5/OmpB protein based vaccine to elicit effective protective immunity againstRickettsia rickettsiiinfections in C3H/HeN mice

Cited by 18 publications

References 16 publications

Evaluation of changes to the Rickettsia rickettsii transcriptome during mammalian infection

Evaluation of changes to the Rickettsia rickettsii transcriptome during mammalian infection

Importancia de las proteínas OmpA y OmpB en el desarrollo de vacunas contra la rickettsiosis

Rickettsia

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