scholarly journals The infectivity gene bbk13 is important for multiple phases of the Borrelia burgdorferi enzootic cycle

2021 ◽  
Author(s):  
George F. Aranjuez ◽  
Amanda G. Lasseter ◽  
Mollie W. Jewett
Keyword(s):  
Borrelia Burgdorferi ◽  
Ixodes Scapularis ◽  
Feeding Activity ◽  
Molecular Genetic ◽  
Population Expansion ◽  
Tick Feeding ◽  
Disseminated Infection ◽  
Multi Stage ◽  
Pathogen Vector ◽  
Enzootic Cycle

Lyme disease is a multi-stage inflammatory disease caused by the spirochete Borrelia burgdorferi transmitted through the bite of an infected Ixodes scapularis tick. We previously discovered a B. burgdorferi infectivity gene, bbk13 , that facilitates mammalian infection by promoting spirochete population expansion in the skin inoculation site. Initial characterization of bbk13 was carried out using an intradermal needle inoculation model of mouse infection, which does not capture the complex interplay of the pathogen-vector-host triad of natural transmission. Herein, we aimed to understand the role of bbk13 in the enzootic cycle of B. burgdorferi . B. burgdorferi lacking bbk13 were unable to be acquired by naive larvae fed on needle inoculated mice. Using a capsule-feeding approach to restrict tick feeding activity to a defined skin site, we determined that delivery by tick bite alleviated the population expansion defect in the skin observed after needle inoculation of Δ bbk13 B. burgdorferi . Despite overcoming the early barrier in the skin, Δ bbk13 B. burgdorferi remained attenuated for distal tissue colonization after tick transmission. Disseminated infection of Δ bbk13 B. burgdorferi was improved in needle inoculated immunocompromised mice. Together, we established that bbk13 is crucial to the maintenance of B. burgdorferi in the enzootic cycle and that bbk13 is necessary beyond early infection in the skin, likely contributing to host immune evasion. Moreover, our data highlight the critical interplay between the pathogen, vector, and host as well as the distinct molecular genetic requirements for B. burgdorferi to survive at the pathogen-vector-host interface and to achieve productive disseminated infection.

scholarly journals Motor Rotation Is Essential for the Formation of the Periplasmic Flagellar Ribbon, Cellular Morphology, and Borrelia burgdorferi Persistence within Ixodes scapularis Tick and Murine Hosts

2015 ◽  
Vol 83 (5) ◽  
pp. 1765-1777 ◽  
Author(s):  
Syed Z. Sultan ◽  
Padmapriya Sekar ◽  
Xiaowei Zhao ◽  
Akarsh Manne ◽  
Jun Liu ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Ixodes Scapularis ◽  
Mutant Cell ◽  
Cellular Morphology ◽  
Flagellar Motor ◽  
Tick Feeding ◽  
Content Type ◽  
Wave Morphology ◽  
Periplasmic Flagella ◽  
Mutant Cells

Borrelia burgdorferimust migrate within and between its arthropod and mammalian hosts in order to complete its natural enzootic cycle. During tick feeding, the spirochete transmits from the tick to the host dermis, eventually colonizing and persisting within multiple, distant tissues. This dissemination modality suggests that flagellar motor rotation and, by extension, motility are crucial for infection. We recently reported that a nonmotileflaBmutant that lacks periplasmic flagella is rod shaped and unable to infect mice by needle or tick bite. However, those studies could not differentiate whether motor rotation or merely the possession of the periplasmic flagella was crucial for cellular morphology and host persistence. Here, we constructed and characterized amotBmutant that is nonmotile but retains its periplasmic flagella. Even though ΔmotBbacteria assembled flagella, part of the mutant cell is rod shaped. Cryoelectron tomography revealed that the flagellar ribbons are distorted in the mutant cells, indicating that motor rotation is essential for spirochetal flat-wave morphology. The ΔmotBcells are unable to infect mice, survive in the vector, or migrate out of the tick. Coinfection studies determined that the presence of these nonmotile ΔmotBcells has no effect on the clearance of wild-type spirochetes during murine infection and vice versa. Together, our data demonstrate that while flagellar motor rotation is necessary for spirochetal morphology and motility, the periplasmic flagella display no additional properties related to immune clearance and persistence within relevant hosts.

scholarly journals Borrelia burgdorferi infection modifies protein content in saliva of Ixodes scapularis nymphs

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tae Kwon Kim ◽  
Lucas Tirloni ◽  
Emily Bencosme-Cuevas ◽  
Tae Heung Kim ◽  
Jolene K. Diedrich ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Protein Content ◽  
Mammalian Cells ◽  
Protein Identification ◽  
Ixodes Scapularis ◽  
Tick Feeding ◽  
Tick Saliva ◽  
Feeding Site ◽  
Copper Zinc Superoxide Dismutase ◽  
Glycolysis Pathway

Abstract Background Lyme disease (LD) caused by Borrelia burgdorferi is the most prevalent tick-borne disease. There is evidence that vaccines based on tick proteins that promote tick transmission of B. burgdorferi could prevent LD. As Ixodes scapularis nymph tick bites are responsible for most LD cases, this study sought to identify nymph tick saliva proteins associated with B. burgdorferi transmission using LC-MS/MS. Tick saliva was collected using a non-invasive method of stimulating ticks (uninfected and infected: unfed, and every 12 h during feeding through 72 h, and fully-fed) to salivate into 2% pilocarpine-PBS for protein identification using LC-MS/MS. Results We identified a combined 747 tick saliva proteins of uninfected and B. burgdorferi infected ticks that were classified into 25 functional categories: housekeeping-like (48%), unknown function (18%), protease inhibitors (9%), immune-related (6%), proteases (8%), extracellular matrix (7%), and small categories that account for <5% each. Notably, B. burgdorferi infected ticks secreted high number of saliva proteins (n=645) than uninfected ticks (n=376). Counter-intuitively, antimicrobial peptides, which function to block bacterial infection at tick feeding site were suppressed 23-85 folds in B. burgdorferi infected ticks. Similar to glycolysis enzymes being enhanced in mammalian cells exposed to B. burgdorferi : eight of the 10-glycolysis pathway enzymes were secreted at high abundance by B. burgdorferi infected ticks. Of significance, rabbits exposed to B. burgdorferi infected ticks acquired potent immunity that caused 40-60% mortality of B. burgdorferi infected ticks during the second infestation compared to 15-28% for the uninfected. This might be explained by ELISA data that show that high expression levels of immunogenic proteins in B. burgdorferi infected ticks. Conclusion Data here suggest that B. burgdorferi infection modified protein content in tick saliva to promote its survival at the tick feeding site. For instance, enzymes; copper/zinc superoxide dismutase that led to production of H2O2 that is toxic to B. burgdorferi were suppressed, while, catalase and thioredoxin that neutralize H2O2, and pyruvate kinase which yields pyruvate that protects Bb from H2O2 killing were enhanced. We conclude data here is an important resource for discovery of effective antigens for a vaccine to prevent LD.

scholarly journals Antibodies against EGF-like domains in Ixodes scapularis BM86 orthologs impact tick feeding and survival of Borrelia burgdorferi

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juraj Koči ◽  
Sandhya Bista ◽  
Payal Chirania ◽  
Xiuli Yang ◽  
Chrysoula Kitsou ◽  
...  
Keyword(s):  
Rna Interference ◽  
Growth Factor ◽  
Borrelia Burgdorferi ◽  
Ixodes Scapularis ◽  
Biological Significance ◽  
Sensu Stricto ◽  
Tick Feeding ◽  
Epidermal Growth ◽  
Tick Vaccine ◽  
Multiple Pathogens

AbstractIxodes scapularis ticks transmit multiple pathogens, including Borrelia burgdorferi sensu stricto, and encode many proteins harboring epidermal growth factor (EGF)-like domains. We show that I. scapularis produces multiple orthologs for Bm86, a widely studied tick gut protein considered as a target of an anti-tick vaccine, herein termed as Is86. We show that Is86 antigens feature at least three identifiable regions harboring EGF-like domains (termed as EGF-1, EGF-2, and EGF-3) and are differentially upregulated during B. burgdorferi infection. Although the RNA interference-mediated knockdown of Is86 genes did not show any influences on tick engorgement or B. burgdorferi sensu stricto persistence, the immunization of murine hosts with specific recombinant EGF antigens marginally reduced spirochete loads in the skin, in addition to affecting tick blood meal engorgement and molting. However, given the borderline impact of EGF immunization on tick engorgement and pathogen survival in the vector, it is unlikely that these antigens, at least in their current forms, could be developed as potential vaccines. Further investigations of the biological significance of Is86 (and other tick antigens) would enrich our knowledge of the intricate biology of ticks, including their interactions with resident pathogens, and contribute to the development of anti-tick measures to combat tick-borne illnesses.

scholarly journals Role of the Surface Lipoprotein BBA07 in the Enzootic Cycle of Borrelia burgdorferi

2010 ◽  
Vol 78 (7) ◽  
pp. 2910-2918 ◽  
Author(s):  
Haijun Xu ◽  
Ming He ◽  
Jane Jingyuan He ◽  
X. Frank Yang
Keyword(s):  
Borrelia Burgdorferi ◽  
Protein Profile ◽  
Mammalian Host ◽  
Tick Feeding ◽  
Tick Transmission ◽  
Nymphal Tick ◽  
Encoding Gene ◽  
Enzootic Cycle

ABSTRACT Borrelia burgdorferi, the Lyme disease pathogen, dramatically alters its protein profile when it is transmitted between ticks and mammals. Several differentially expressed proteins have been shown to be critical for the enzootic cycle of B. burgdorferi. In this study, we demonstrated that expression of the surface lipoprotein-encoding gene bba07 is induced by an elevated temperature and a reduced pH during in vitro cultivation, as well as during nymphal tick feeding. Expression of bba07 is regulated by the Rrp2-RpoN-RpoS pathway, a central regulatory network that is activated during nymphal feeding. By generating a bba07 mutant of an infectious strain of B. burgdorferi, we demonstrated that although BBA07-deficient spirochetes were capable of infecting mice via needle inoculation and surviving in ticks, they were defective in infection of mammals via tick transmission. Complementation of the bba07 mutant with a wild-type copy of bba07 partially restored the transmission defect of the bba07 mutant. Based on these findings, we concluded that the surface lipoprotein BBA07 is produced during tick feeding and facilitates optimal transmission of B. burgdorferi from the tick vector to a mammalian host.

scholarly journals Monitoring the patterns of submission and presence of tick-borne pathogens in Ixodes scapularis collected from humans and companion animals in Ontario, Canada (2011–2017)

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Mark P. Nelder ◽  
Curtis B. Russell ◽  
Antonia Dibernardo ◽  
Katie M. Clow ◽  
Steven Johnson ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Regression Models ◽  
Ixodes Scapularis ◽  
Companion Animals ◽  
Companion Animal ◽  
Babesia Microti ◽  
Blacklegged Tick ◽  
Host Type ◽  
Animal Populations ◽  
Pathogen Prevalence

Abstract Background The universal nature of the human–companion animal relationship and their shared ticks and tick-borne pathogens offers an opportunity for improving public and veterinary health surveillance. With this in mind, we describe the spatiotemporal trends for blacklegged tick (Ixodes scapularis) submissions from humans and companion animals in Ontario, along with pathogen prevalence. Methods We tested tick samples submitted through passive surveillance (2011–2017) from humans and companion animals for Borrelia burgdorferi, Borrelia miyamotoi, Anaplasma phagocytophilum and Babesia microti. We describe pathogen prevalence in ticks from humans and from companion animals and constructed univariable Poisson and negative binomial regression models to explore the spatiotemporal relationship between the rates of tick submissions by host type. Results During the study, there were 17,230 blacklegged tick samples submitted from humans and 4375 from companion animals. Tick submission rates from companion animals were higher than expected in several public health units (PHUs) lacking established tick populations, potentially indicating newly emerging populations. Pathogen prevalence in ticks was higher in PHUs where established blacklegged tick populations exist. Borrelia burgdorferi prevalence was higher in ticks collected from humans (maximum likelihood estimate, MLE = 17.5%; 95% confidence interval, CI 16.97–18.09%) than from companion animals (9.9%, 95% CI 9.15–10.78%). There was no difference in pathogen prevalence in ticks by host type for the remaining pathogens, which were found in less than 1% of tested ticks. The most common co-infection B. burgdorferi + B. miyamotoi occurred in 0.11% of blacklegged ticks from humans and animals combined. Borrelia burgdorferi prevalence was higher in unengorged (21.9%, 95% CI 21.12–22.65%) than engorged ticks (10.0%, 95% CI 9.45–10.56%). There were no consistent and significant spatiotemporal relationships detected via regression models between the annual rates of submission of each host type. Conclusions While B. burgdorferi has been present in blacklegged ticks in Ontario for several decades, other tick-borne pathogens are also present at low prevalence. Blacklegged tick and pathogen surveillance data can be used to monitor risk in human and companion animal populations, and efforts are under consideration to unite surveillance efforts for the different target populations. Graphic Abstract

Coinfection of Ixodes scapularis (Acari: Ixodidae) Nymphs With Babesia spp. (Piroplasmida: Babesiidae) and Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) in Wisconsin

2021 ◽  
Author(s):  
T E Zembsch ◽  
X Lee ◽  
G M Bron ◽  
L C Bartholomay ◽  
S M Paskewitz
Keyword(s):  
United States ◽  
Borrelia Burgdorferi ◽  
Ixodes Scapularis ◽  
Healthcare Providers ◽  
Positive Association ◽  
Sensu Stricto ◽  
Babesia Microti ◽  
Tick Bites ◽  
The Family ◽  
Babesia Spp

Abstract Borrelia burgdorferi, the spirochete that causes Lyme disease, is endemic and widespread in Wisconsin. Research in the northeastern United States has revealed a positive association between Babesia microti, the main pathogen that causes babesiosis in humans, and Bo. burgdorferi in humans and in ticks. This study was conducted to examine associations between the disease agents in the Upper midwestern United States. Ixodes scapularis Say nymphs (N = 2,858) collected between 2015 and 2017 from nine locations in Wisconsin were tested for Babesia spp. and Borrelia spp. using real-time PCR. Two species of Babesia were detected; Ba. microti and Babesia odocoilei (a parasite of members of the family Cervidae). Prevalence of infection at the nine locations ranged from 0 to 13% for Ba. microti, 11 to 31% for Bo. burgdorferi sensu stricto, and 5.7 to 26% for Ba. odocoilei. Coinfection of nymphs with Bo. burgdorferi and Ba. odocoilei was detected in eight of the nine locations and significant positive associations were observed in two of the eight locations. The prevalence of nymphal coinfection with both and Bo. burgdorferi and Ba. microti ranged from 0.81 to 6.5%. These two pathogens were significantly positively associated in one of the five locations where both pathogens were detected. In the other four locations, the observed prevalence of coinfection was higher than expected in all but one site-year. Clinics and healthcare providers should be aware of the association between Ba. microti and Bo. burgdorferi pathogens when treating patients who report tick bites.

scholarly journals An efficient microinjection method to generate human anaplasmosis agent Anaplasma phagocytophilum-infected ticks

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vikas Taank ◽  
Ellango Ramasamy ◽  
Hameeda Sultana ◽  
Girish Neelakanta
Keyword(s):  
Anaplasma Phagocytophilum ◽  
Ixodes Scapularis ◽  
In Vitro Cultures ◽  
Transmission Dynamics ◽  
Tick Feeding ◽  
Nymphal Stage ◽  
Bacterial Colony ◽  
Obligate Intracellular ◽  
Transstadial Transmission

Abstract Ticks are important vectors that transmit several pathogens including human anaplasmosis agent, Anaplasma phagocytophilum. This bacterium is an obligate intracellular rickettsial pathogen. An infected reservoir animal host is often required for maintenance of this bacterial colony and as a source for blood to perform needle inoculations in naïve animals for tick feeding studies. In this study, we report an efficient microinjection method to generate A. phagocytophilum-infected ticks in laboratory conditions. The dense-core (DC) form of A. phagocytophilum was isolated from in vitro cultures and injected into the anal pore of unfed uninfected Ixodes scapularis nymphal ticks. These ticks successfully transmitted A. phagocytophilum to the murine host. The bacterial loads were detected in murine blood, spleen, and liver tissues. In addition, larval ticks successfully acquired A. phagocytophilum from mice that were previously infected by feeding with DC-microinjected nymphal ticks. Transstadial transmission of A. phagocytophilum from larvae to nymphal stage was also evident in these ticks. Taken together, our study provides a timely, rapid, and an efficient method not only to generate A. phagocytophilum-infected ticks but also provides a tool to understand acquisition and transmission dynamics of this bacterium and perhaps other rickettsial pathogens from medically important vectors.

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