Dataset Information

Frankenbacteriosis targeting interactions between pathogen and symbiont to control infection in the tick vector.

ABSTRACT: Tick microbiota can be targeted for the control of tick-borne diseases such as human granulocytic anaplasmosis (HGA) caused by model pathogen, Anaplasma phagocytophilum. Frankenbacteriosis is inspired by Frankenstein and defined here as paratransgenesis of tick symbiotic/commensal bacteria to mimic and compete with tick-borne pathogens. Interactions between A. phagocytophilum and symbiotic Sphingomonas identified by metaproteomics analysis in Ixodes scapularis midgut showed competition between both bacteria. Consequently, Sphingomonas was selected for frankenbacteriosis for the control of A. phagocytophilum infection and transmission. The results showed that Franken Sphingomonas producing A. phagocytophilum major surface protein 4 (MSP4) mimic pathogen and reduce infection in ticks by competition and interaction with cell receptor components of infection. Franken Sphingomonas-MSP4 transovarial and trans-stadial transmission suggests that tick larvae with genetically modified Franken Sphingomonas-MSP4 could be produced in the laboratory and released in the field to compete and replace the wildtype populations with associated reduction in pathogen infection/transmission and HGA disease risks.

SUBMITTER: Mazuecos L

PROVIDER: S-EPMC10165458 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Frankenbacteriosis targeting interactions between pathogen and symbiont to control infection in the tick vector.

Mazuecos Lorena L Alberdi Pilar P Hernández-Jarguín Angélica A Contreras Marinela M Villar Margarita M Cabezas-Cruz Alejandro A Simo Ladislav L González-García Almudena A Díaz-Sánchez Sandra S Neelakanta Girish G Bonnet Sarah I SI Fikrig Erol E de la Fuente José J

iScience 20230418 5

Tick microbiota can be targeted for the control of tick-borne diseases such as human granulocytic anaplasmosis (HGA) caused by model pathogen, Anaplasma phagocytophilum. Frankenbacteriosis is inspired by Frankenstein and defined here as paratransgenesis of tick symbiotic/commensal bacteria to mimic and compete with tick-borne pathogens. Interactions between A. phagocytophilum and symbiotic Sphingomonas identified by metaproteomics analysis in Ixodes scapularis midgut ...[more]

PMID: 37168564

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Project description:BACKGROUND: Ticks represent a significant health risk to animals and humans due to the variety of pathogens they can transmit during feeding. The traditional use of chemicals to control ticks has serious drawbacks, including the selection of acaricide-resistant ticks and environmental contamination with chemical residues. Vaccination with the tick midgut antigen BM86 was shown to be a good alternative for cattle tick control. However, results vary considerably between tick species and geographic location. Therefore, new antigens are required for the development of vaccines controlling both tick infestations and pathogen infection/transmission. Tick proteins involved in tick-pathogen interactions may provide good candidate protective antigens for these vaccines, but appropriate screening procedures are needed to select the best candidates. METHODS: In this study, we selected proteins involved in tick-Anaplasma (Subolesin and SILK) and tick-Babesia (TROSPA) interactions and used in vitro capillary feeding to characterize their potential as antigens for the control of cattle tick infestations and infection with Anaplasma marginale and Babesia bigemina. Purified rabbit polyclonal antibodies were generated against recombinant SUB, SILK and TROSPA and added to uninfected or infected bovine blood to capillary-feed female Rhipicephalus (Boophilus) microplus ticks. Tick weight, oviposition and pathogen DNA levels were determined in treated and control ticks. RESULTS: The specificity of purified rabbit polyclonal antibodies against tick recombinant proteins was confirmed by Western blot and against native proteins in tick cell lines and tick tissues using immunofluorescence. Capillary-fed ticks ingested antibodies added to the blood meal and the effect of these antibodies on tick weight and oviposition was shown. However, no effect was observed on pathogen DNA levels. CONCLUSIONS: These results highlighted the advantages and some of the disadvantages of in vitro tick capillary feeding for the characterization of candidate tick protective antigens. While an effect on tick weight and oviposition was observed, the effect on pathogen levels was not evident probably due to high tick-to-tick variations among other factors. Nevertheless, these results together with previous results of RNA interference functional studies suggest that these proteins are good candidate vaccine antigens for the control of R. microplus infestations and infection with A. marginale and B. bigemina.

Project description:Anaplasma phagocytophilum is an obligate intracellular rickettsial pathogen that infects humans and animals. The black-legged tick Ixodes scapularis acts as a vector and transmits this bacterium to the vertebrate host. Upon entry into a host cell, A. phagocytophilum resides and multiplies in a host-derived vacuole called morulae. There is not much information available on the molecules that play an important role(s) in A. phagocytophilum entry and formation of these morulae in tick cells. In this study, we provide evidence that tick vesicular-associated membrane proteins, VAMP3 and VAMP4, play important roles in this phenomenon. Quantitative real-time polymerase chain reaction (QRT-PCR) analysis showed that both vamp3 and vamp4 transcripts are significantly upregulated at early time points of A. phagocytophilum infection in tick cells. We noted that both VAMP3 and VAMP4 predominantly localized to the A. phagocytophilum-containing vacuole. RNAi-mediated silencing of vamp3 and/or vamp4 expression, followed by confocal microscopy and expression analysis, indicated an impairment in A. phagocytophilum morulae formation in tick cells. We also noted that VAMP3 and VAMP4 play a role in the A. phagocytophilum persistent infection of ticks and tick cells. Furthermore, RNAi-mediated silencing of expression of arthropod vamp3 and vamp4 affected bacterial acquisition from an infected murine host to ticks. Collectively, this study not only provides evidence on the role of arthropod vesicular-associated membrane proteins in A. phagocytophilum morulae formation in tick cells but also demonstrates that these proteins are important for bacterial acquisition from an infected vertebrate host into ticks.ImportanceAnaplasma phagocytophilum is a tick-borne pathogen primarily transmitted by black-legged Ixodes scapularis ticks to humans and animals. This bacterium enters host cells, forms a host-derived vacuole, and multiplies within this vacuole. The molecules that are critical in the formation of host-derived vacuole in tick cells is currently not well-characterized. In this study, we provide evidence that arthropod vesicular-associated membrane proteins, VAMP3 and VAMP4, are critical for A. phagocytophilum early and persistent infection in tick cells. These arthropod proteins are important for the formation of host-derived vacuoles in tick cells. Our study also provides evidence that these proteins are important for A. phagocytophilum acquisition from the infected murine host into ticks. Characterization of tick molecules important in bacterial entry and/or survival in the vector host could lead to the development of strategies to target this and perhaps other rickettsial pathogens.

Project description:The blacklegged tick Ixodes scapularis is the primary vector for the bacterium causing Lyme disease in eastern North America and for other medically important pathogens. This species is vulnerable to attack by fungal pathogens and arthropod predators, but the impacts of interactions between biocontrol agents have not been examined. The biocontrol agent Met52®, containing the entomopathogenic fungus Metarhizium brunneum (=M. anisopliae), controls blacklegged ticks with efficacy comparable to chemical acaricides. The brush-legged wolf spider Schizocosa ocreata is a predator of I. scapularis that reduces their survival under field conditions. We conducted a field microcosm experiment to assess the compatibility of Met52 and S. ocreata as tick biocontrol agents. We compared the fits of alternative models in predicting survival of unfed (flat) and blood-fed (engorged) nymphs. We found the strongest support for a model that included negative effects of Met52 and S. ocreata on flat nymph survival. We found evidence for interference between biocontrol agents, with Met52 reducing spider survival, but we did not find a significant interaction effect between the two agents on nymph survival. For engorged nymphs, low recovery rates resulted in low statistical power to detect possible effects of biocontrol agents. We found that nymph questing activity was lower when the spider was active above the leaf litter than when the spider was unobserved. This provides the first evidence that predation cues might affect behavior important for tick fitness and pathogen transmission. This study presents field microcosm evidence that the biopesticide Met52 and spider Schizocosa ocreata each reduced survival of blacklegged ticks Ixodes scapularis. Met52 reduced spider survival. Potential interference between Met52 and the spider should be examined at larger scales, where overlap patterns may differ. Ticks were more likely to quest when the spider was inactive, suggesting the ticks changed their behavior to reduce danger.

Project description:BACKGROUND: The tick-borne pathogen Anaplasma marginale, which is endemic worldwide, is the type species of the genus Anaplasma (Rickettsiales: Anaplasmataceae). Rhipicephalus (Boophilus) microplus is the most important tick vector of A. marginale in tropical and subtropical regions of the world. Despite extensive characterization of the genetic diversity in A. marginale geographic strains using major surface protein sequences, little is known about the biogeography and evolution of A. marginale and other Anaplasma species. For A. marginale, MSP1a was shown to be involved in vector-pathogen and host-pathogen interactions and to have evolved under positive selection pressure. The MSP1a of A. marginale strains differs in molecular weight because of a variable number of tandem 23-31 amino acid repeats and has proven to be a stable marker of strain identity. While phylogenetic studies of MSP1a repeat sequences have shown evidence of A. marginale-tick co-evolution, these studies have not provided phylogeographic information on a global scale because of the high level of MSP1a genetic diversity among geographic strains. RESULTS: In this study we showed that the phylogeography of A. marginale MSP1a sequences is associated with world ecological regions (ecoregions) resulting in different evolutionary pressures and thence MSP1a sequences. The results demonstrated that the MSP1a first (R1) and last (RL) repeats and microsatellite sequences were associated with world ecoregion clusters with specific and different environmental envelopes. The evolution of R1 repeat sequences was found to be under positive selection. It is hypothesized that the driving environmental factors regulating tick populations could act on the selection of different A. marginale MSP1a sequence lineages, associated to each ecoregion. CONCLUSION: The results reported herein provided the first evidence that the evolution of A. marginale was linked to ecological traits affecting tick vector performance. These results suggested that some A. marginale strains have evolved under conditions that support pathogen biological transmission by R. microplus, under different ecological traits which affect performance of R. microplus populations. The evolution of other A. marginale strains may be linked to transmission by other tick species or to mechanical transmission in regions where R. microplus is currently eradicated. The information derived from this study is fundamental toward understanding the evolution of other vector-borne pathogens.

Dataset Information

Frankenbacteriosis targeting interactions between pathogen and symbiont to control infection in the tick vector.

Publications

Frankenbacteriosis targeting interactions between pathogen and symbiont to control infection in the tick vector.

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