Rickettsia rickettsii Whole-Cell Antigens Offer Protection against Rocky Mountain Spotted Fever in the Canine Host

Alhassan, Andy; Liu, Huitao; McGill, Jodi L.; Cerezo, Argiñe; Jakkula, Laxmi U. M. R.; Nair, Arathy D. S.; Winkley, Emma; Olson, Sally; Marlow, Denver; Sahni, Abha; Narra, Hema P.; Sahni, Sanjeev K.; Henningson, Jamie; Ganta, Roman R.

doi:10.1128/iai.00628-18

Cited by 22 publications

(22 citation statements)

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“…In addition, our results point out that policies encouraging dog restraint to limit the free trafficking of dogs and ticks across communities may have implications as means to limit RMSF risk, rather than the restriction of the number of owned dogs. Finally, use of a vaccine in dogs, such as the recently described whole-cell inactivated antigen vaccine [49], could also reduce risk to humans and dogs by boosting canine herd immunity.…”

Section: Plos Onementioning

confidence: 99%

An exploratory analysis of demography and movement patterns of dogs: New insights in the ecology of endemic Rocky Mountain-Spotted Fever in Mexicali, Mexico

et al. 2020

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An outbreak of Rocky Mountain spotted fever (RMSF) transmitted by the brown dog tick (Rhipicephalus sanguineus sensu lato) has emerged as a major human and animal health concern in Mexicali, Mexico. Due to high rates of brown dog tick infestation, susceptibility, and association with humans, dogs serve as sentinels and have a key role in the ecology of RMSF. A cross-sectional household questionnaire study was conducted in six rural and urban locations to characterize dog ecology and demography in RMSF high-and low-risk areas of Mexicali. In addition, we tracked movement patterns of 16 dogs using a GPS data logger. Of 253 households, 73% owned dogs, and dog ownership tended to be higher in high-risk areas, with a mean dog:human ratio of 0.43, compared with 0.3 in low-risk areas. Dogs in high-risk areas had higher fecundity and roamed more, but the dog density and numbers of free-roaming dogs were comparable. There was a higher proportion of younger dogs and lower proportion of older dogs in high-risk areas. The high proportion of immunologically naïve puppies in high risk areas could result in a lack of herd immunity leading to a more vulnerable dog and human population. The marked increase of space use of freeroaming dogs in high-risk areas suggests that unrestrained dogs could play an important role in spreading ticks and pathogens. As means to limit RMSF risk, practical changes could include increased efforts for spay-neuter and policies encouraging dog restraint to limit canine roaming and spread of ticks across communities; due to dog density is less impactful such policies may be more useful than restrictions on the number of owned dogs.

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Section: Plos Onementioning

confidence: 99%

An exploratory analysis of demography and movement patterns of dogs: New insights in the ecology of endemic Rocky Mountain-Spotted Fever in Mexicali, Mexico

et al. 2020

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“…Stocks of Rickettsia conorii were prepared in Vero E6 cells using established protocols and procedures [90]. R. conorii stocks prepared from the yolk-sacs of fertilized eggs as described earlier [91] were used for further propagation in Vero cells. Briefly, confluent Vero cell monolayers in DMEM containing 2% FBS were infected with R. conorii and incubated at 35°C, 5% CO 2 .…”

Section: Preparation and Quantification Of R Conorii Stocksmentioning

confidence: 99%

Comparative transcriptomic analysis of Rickettsia conorii during in vitro infection of human and tick host cells

et al. 2020

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Background Pathogenic Rickettsia species belonging to the spotted fever group are arthropod-borne, obligate intracellular bacteria which exhibit preferential tropism for host microvascular endothelium in the mammalian hosts, resulting in disease manifestations attributed primarily to endothelial damage or dysfunction. Although rickettsiae are known to undergo evolution through genomic reduction, the mechanisms by which these pathogens regulate their transcriptome to ensure survival in tick vectors and maintenance by transovarial/transstadial transmission, in contrast to their ability to cause debilitating infections in human hosts remain unknown. In this study, we compare the expression profiles of rickettsial sRNAome/transcriptome and determine the transcriptional start sites (TSSs) of R. conorii transcripts during in vitro infection of human and tick host cells. Results We performed deep sequencing on total RNA from Amblyomma americanum AAE2 cells and human microvascular endothelial cells (HMECs) infected with R. conorii. Strand-specific RNA sequencing of R. conorii transcripts revealed the expression 32 small RNAs (Rc_sR’s), which were preferentially expressed above the limit of detection during tick cell infection, and confirmed the expression of Rc_sR61, sR71, and sR74 by quantitative RT-PCR. Intriguingly, a total of 305 and 132 R. conorii coding genes were differentially upregulated (> 2-fold) in AAE2 cells and HMECs, respectively. Further, enrichment for primary transcripts by treatment with Terminator 5′-Phosphate-dependent Exonuclease resulted in the identification of 3903 and 2555 transcription start sites (TSSs), including 214 and 181 primary TSSs in R. conorii during the infection to tick and human host cells, respectively. Seventy-five coding genes exhibited different TSSs depending on the host environment. Finally, we also observed differential expression of 6S RNA during host-pathogen and vector-pathogen interactions in vitro, implicating an important role for this noncoding RNA in the regulation of rickettsial transcriptome depending on the supportive host niche. Conclusions In sum, the findings of this study authenticate the presence of novel Rc_sR’s in R. conorii, reveal the first evidence for differential expression of coding transcripts and utilization of alternate transcriptional start sites depending on the host niche, and implicate a role for 6S RNA in the regulation of coding transcriptome during tripartite host-pathogen-vector interactions.

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“…However, ticks and transmitted pathogens continue to be a major health problem in dogs and other companion animals that require the development of effective vaccines (Otranto, 2018). Previous experiments have shown the possibility of using vaccines with tick gut protein extracts, Subolesin/Akirin and Bm96 for the control of Rhipicephalus sanguineus infestations in dogs (de la Fuente et al, 2015), and with pathogen-derived antigens for the control of VBD (e.g., Alhassan et al, 2018; Grosenbaugh et al, 2018). Nevertheless, vaccines for the control of tick infestations and transmitted diseases in companion animals have not been registered and commercialized.…”

Section: Introductionmentioning

confidence: 99%

A Vaccinomics Approach for the Identification of Tick Protective Antigens for the Control of Ixodes ricinus and Dermacentor reticulatus Infestations in Companion Animals

2019

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Ticks and tick-borne pathogens affect health and welfare of companion animals worldwide, and some human tick-borne diseases are associated with exposure to domestic animals. Vaccines are the most environmentally friendly alternative to acaracides for the control of tick infestations, and to reduce the risk for tick-borne diseases affecting human and animal health. However, vaccines have not been developed or successfully implemented for most vector-borne diseases. The main limitation for the development of effective vaccines is the identification of protective antigens. To address this limitation, in this study we used an experimental approach combining vaccinomics based on transcriptomics and proteomics data with vaccination trials for the identification of tick protective antigens. The study was focused on Ixodes ricinus and Dermacentor reticulatus that infest humans, companion animals and other domestic and wild animals, and transmit disease-causing pathogens. Tick larvae and adult salivary glands were selected for analysis to target tick organs and developmental stages playing a key role during tick life cycle and pathogen infection and transmission. Two I. ricinus (heme lipoprotein and uncharacterized secreted protein) and five D. reticulatus (glypican-like protein, secreted protein involved in homophilic cell adhesion, sulfate/anion exchanger, signal peptidase complex subunit 3, and uncharacterized secreted protein) proteins were identified as the most effective protective antigens based on the criteria of vaccine E > 80%. The putative function of selected protective antigens, which are involved in different biological processes, resulted in vaccines affecting multiple tick developmental stages. These results suggested that the combination of some of these antigens might be considered to increase vaccine efficacy through antigen synergy for the control of tick infestations and potentially affecting pathogen infection and transmission. These antigens were proposed for commercial vaccine development for the control of tick infestations in companion animals, and potentially in other hosts for these tick species.

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Rickettsia rickettsii Whole-Cell Antigens Offer Protection against Rocky Mountain Spotted Fever in the Canine Host

Abstract: Rocky Mountain spotted fever (RMSF) is a potentially fatal tick-borne disease in people and dogs. RMSF is reported in the United States and several countries in North, Central, and South America.

Cited by 22 publications

References 66 publications

An exploratory analysis of demography and movement patterns of dogs: New insights in the ecology of endemic Rocky Mountain-Spotted Fever in Mexicali, Mexico

An exploratory analysis of demography and movement patterns of dogs: New insights in the ecology of endemic Rocky Mountain-Spotted Fever in Mexicali, Mexico

Comparative transcriptomic analysis of Rickettsia conorii during in vitro infection of human and tick host cells

A Vaccinomics Approach for the Identification of Tick Protective Antigens for the Control of Ixodes ricinus and Dermacentor reticulatus Infestations in Companion Animals

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