Nejvíce citovaný článek - PubMed ID 26673735
Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis
Lyme disease (LD) spirochetes are well known to be able to disseminate into the tissues of infected hosts, including humans. The diverse strategies used by spirochetes to avoid the host immune system and persist in the host include active immune suppression, induction of immune tolerance, phase and antigenic variation, intracellular seclusion, changing of morphological and physiological state in varying environments, formation of biofilms and persistent forms, and, importantly, incursion into immune-privileged sites such as the brain. Invasion of immune-privileged sites allows the spirochetes to not only escape from the host immune system but can also reduce the efficacy of antibiotic therapy. Here we present a case of the detection of spirochetal DNA in multiple loci in a LD patient's post-mortem brain. The presence of co-infection with Borrelia burgdorferi sensu stricto and Borrelia garinii in this LD patient's brain was confirmed by PCR. Even though both spirochete species were simultaneously present in human brain tissue, the brain regions where the two species were detected were different and non-overlapping. The presence of atypical spirochete morphology was noted by immunohistochemistry of the brain samples. Atypical morphology was also found in the tissues of experimentally infected mice, which were used as a control.
- Klíčová slova
- Borrelia burgdorferi, Borrelia garinii, Lyme disease, co-infection, human brain, immunohistochemistry, molecular detection, neuroborreliosis, persistence,
- MeSH
- Borrelia burgdorferi komplex * genetika MeSH
- Borrelia burgdorferi * genetika MeSH
- Borrelia * genetika MeSH
- lidé MeSH
- lymeská nemoc * MeSH
- mozek MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Ticks transmit a broad spectrum of pathogens, threatening both animal and human health. Tick survival and proliferation are strongly dependent on host selection and suitability. The hard tick Ixodes ricinus, which is widespread throughout most of Europe, is a host generalist capable of feeding on many different vertebrate species. Pasture-kept exotic farm animals may be at a high risk for tick and tick-borne pathogens infestations but research characterizing this is currently lacking. This study focused on the detection of Borrelia spirochetes (including Borrelia miyamotoi) in exotic farm animals. Using nested-PCR with Borrelia-specific primers, 121 serum samples from 54 exotic farm animals of several species bred in four different farms in Bohemia and Moravia (Czechia) were tested. Positive samples were sequenced for the identification of Borrelia species. The prevalence of Borrelia DNA in the samples ranged from 13 to 67%, depending on the sampling site. The sequencing results confirmed the DNA presence of multiple spirochete species from the Borrelia burgdorferi sensu lato complex. Only one sample from an ostrich (Struthio camelus) was found to be positive for Borrelia myiamotoi. The results show that exotic farm animals can serve as hosts for hard ticks and can be infected by Borrelia spirochetes, transmitted by hard ticks. Therefore, these animals could play a relevant role in maintaining Borrelia spirochetes in nature.
- Klíčová slova
- Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Ixodes ricinus, tick, tick hosts, tick-borne pathogens,
- Publikační typ
- časopisecké články MeSH
Lyme borreliosis (LB), caused by spirochetes of the Borrelia burgdorferi sensu lato (s.l.) complex, is one of the most common vector-borne zoonotic diseases in Europe. Knowledge about the enzootic circulation of Borrelia pathogens between ticks and their vertebrate hosts is epidemiologically important and enables assessment of the health risk for the human population. In our project, we focused on the following vertebrate species: European hedgehog (Erinaceus europaeus), Northern white-breasted hedgehog (E. roumanicus), Eurasian red squirrel (Sciurus vulgaris), and Common blackbird (Turdus merula). The cadavers of accidentally killed animals used in this study constitute an available source of biological material, and we have confirmed its potential for wide monitoring of B. burgdorferi s.l. presence and genospecies diversity in the urban environment. High infection rates (90% for E. erinaceus, 73% for E. roumanicus, 91% for S. vulgaris, and 68% for T. merula) were observed in all four target host species; mixed infections by several genospecies were detected on the level of individuals, as well as in particular tissue samples. These findings show the usefulness of multiple tissue sampling as tool for revealing the occurrence of several genospecies within one animal and the risk of missing particular B. burgdorferi s.l. genospecies when looking in one organ alone.
- Klíčová slova
- Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Common blackbird, Eurasian red squirrel, European hedgehog, Northern white-breasted hedgehog,
- Publikační typ
- časopisecké články MeSH
Lyme borreliosis is a bacterial infection that can be spread to humans by infected ticks and may severely affect many organs and tissues. Nearly four decades have elapsed since the discovery of the disease agent called Borrelia burgdorferi. Although there is a plethora of knowledge on the infectious agent and thousands of scientific publications, an effective way on how to combat and prevent Lyme borreliosis has not been found yet. There is no vaccine for humans available, and only one active vaccine program in clinical development is currently running. A spirited search for possible disease interventions is of high public interest as surveillance data indicates that the number of cases of Lyme borreliosis is steadily increasing in Europe and North America. This review provides a condensed digest of the history of vaccine development up to new promising vaccine candidates and strategies that are targeted against Lyme borreliosis, including elements of the tick vector, the reservoir hosts, and the Borrelia pathogen itself.
- Klíčová slova
- Anti-tick strategies, Human pathogen, Lyme borreliosis, Public health, Vaccine candidates,
- MeSH
- bakteriální vakcíny genetika imunologie MeSH
- Borrelia burgdorferi genetika imunologie fyziologie MeSH
- infekce přenášené vektorem MeSH
- klíšťata mikrobiologie MeSH
- lidé MeSH
- lymeská nemoc imunologie mikrobiologie prevence a kontrola MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- bakteriální vakcíny MeSH
The survival of spirochetes from the Borrelia burgdorferi (sensu lato) complex in a hostile environment is achieved by the regulation of differential gene expression in response to changes in temperature, salts, nutrient content, acidity fluctuation, multiple host or vector dependent factors, and leads to the formation of dormant subpopulations of cells. From the other side, alterations in the level of gene expression in response to antibiotic pressure leads to the establishment of a persisters subpopulation. Both subpopulations represent the cells in different physiological states. "Dormancy" and "persistence" do share some similarities, e.g. both represent cells with low metabolic activity that can exist for extended periods without replication, both constitute populations with different gene expression profiles and both differ significantly from replicating forms of spirochetes. Persisters are elusive, present in low numbers, morphologically heterogeneous, multi-drug-tolerant cells that can change with the environment. The definition of "persisters" substituted the originally-used term "survivors", referring to the small bacterial population of Staphylococcus that survived killing by penicillin. The phenomenon of persisters is present in almost all bacterial species; however, the reasons why Borrelia persisters form are poorly understood. Persisters can adopt varying sizes and shapes, changing from well-known forms to altered morphologies. They are capable of forming round bodies, L-form bacteria, microcolonies or biofilms-like aggregates, which remarkably change the response of Borrelia to hostile environments. Persisters remain viable despite aggressive antibiotic challenge and are able to reversibly convert into motile forms in a favorable growth environment. Persisters are present in significant numbers in biofilms, which has led to the explanation of biofilm tolerance to antibiotics. Considering that biofilms are associated with numerous chronic diseases through their resilient presence in the human body, it is not surprising that interest in persisting cells has consequently accelerated. Certain diseases caused by pathogenic bacteria (e.g. tuberculosis, syphilis or leprosy) are commonly chronic in nature and often recur despite antibiotic treatment. Three decades of basic and clinical research have not yet provided a definite answer to the question: is there a connection between persisting spirochetes and recurrence of Lyme disease in patients?
- Klíčová slova
- Antibiotic treatment, Biofilm, Borrelia burgdorferi, Dormant forms, Lyme disease, Persistent infection, Persisters, Round bodies,
- MeSH
- antibakteriální látky farmakologie MeSH
- biofilmy růst a vývoj MeSH
- Borrelia burgdorferi komplex účinky léků fyziologie MeSH
- lidé MeSH
- lymeská nemoc mikrobiologie MeSH
- mikrobiální viabilita účinky léků MeSH
- recidiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antibakteriální látky MeSH
To understand the response of the Lyme disease spirochete Borrelia burgdorferi exposed to stress conditions and assess the viability of this spirochete, we used a correlative cryo-fluorescence and cryo-scanning microscopy approach. This approach enables simple exposition of bacteria to various experimental conditions that can be stopped at certain time intervals by cryo-immobilization, examination of cell viability without necessity to maintain suitable culture conditions during viability assays, and visualization of structures in their native state at high magnification. We focused on rare and transient events e.g., the formation of round bodies and the presence of membranous blebs in spirochetes exposed to culture medium, host sera either without or with the bacteriolytic effect and water. We described all crucial steps of the workflow, particularly the influence of freeze-etching and accelerating voltage on the visualization of topography. With the help of newly designed cryo-transport device, we achieved greater reproducibility.
- Klíčová slova
- Borrelia burgdorferi, Lyme disease, cryo-fluorescence, cryo-scanning electron microscopy, pleomorphism, round body, viability staining,
- Publikační typ
- časopisecké články MeSH
- MeSH
- bakteriální geny MeSH
- Borrelia burgdorferi genetika izolace a purifikace MeSH
- interakce hostitele a patogenu MeSH
- Ixodidae mikrobiologie MeSH
- lidé MeSH
- lymeská nemoc epidemiologie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- jihovýchod USA epidemiologie MeSH
BACKGROUND: Out of 20 spirochete species from Borrelia burgdorferi sensu lato (s.l.) complex recognized to date some are considered to have a limited distribution, while others are worldwide dispersed. Among those are Borrelia burgdorferi sensu stricto (s.s.) and Borrelia bissettii which are distributed both in North America and in Europe. While B. burgdorferi s.s. is recognized as a cause of Lyme borreliosis worldwide, involvement of B. bissettii in human Lyme disease was not so definite yet. FINDINGS: Multilocus sequence typing of spirochete isolates originating from residents of Georgia and Florida, USA, revealed the presence of two Borrelia burgdorferi sensu stricto strains highly similar to those from endemic Lyme borreliosis regions of the northeastern United States, and an unusual strain that differed from any previously described in Europe or North America. Based on phylogenetic analysis of eight chromosomally located housekeeping genes divergent strain clustered between Borrelia bissettii and Borrelia carolinensis, two species from the B.burgdorferi s.l. complex, widely distributed among the multiple hosts and vector ticks in the southeastern United States. The genetic distance analysis showed a close relationship of the diverged strain to B. bissettii. CONCLUSIONS: Here, we present the analysis of the first North American human originated live spirochete strain that revealed close relatedness to B. bissettii. The potential of B. bissettii to cause human disease, even if it is infrequent, is of importance for clinicians due to the extensive range of its geographic distribution.
- MeSH
- Borrelia burgdorferi komplex MeSH
- Borrelia burgdorferi MeSH
- Borrelia klasifikace genetika izolace a purifikace MeSH
- esenciální geny MeSH
- genotyp MeSH
- lidé MeSH
- lymeská nemoc diagnóza mikrobiologie MeSH
- molekulární sekvence - údaje MeSH
- multilokusová sekvenční typizace * MeSH
- sekvenční analýza DNA MeSH
- shluková analýza MeSH
- Spirochaetales MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Florida MeSH
- Georgia MeSH