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Microbes and Infection Jun 2003Borrelia burgdorferi sensu lato is the causative agent of Lyme disease, which afflicts both humans and some domestic animals. B. burgdorferi, a highly evolved... (Review)
Review
Borrelia burgdorferi sensu lato is the causative agent of Lyme disease, which afflicts both humans and some domestic animals. B. burgdorferi, a highly evolved extracellular pathogen, uses several strategies to survive in a complex enzootic cycle involving a diverse range of hosts. This review focuses on the unique adaptive features of B. burgdorferi, which are central to establishing a successful spirochetal infection within arthropod and vertebrate hosts. We also discuss the regulatory mechanisms linked with the development of molecular adaptation of spirochetes within different host environments.
Topics: Adaptation, Physiological; Animals; Arachnid Vectors; Borrelia burgdorferi; Disease Vectors; Gene Expression Regulation, Bacterial; Host-Parasite Interactions; Lyme Disease; Ticks; Vertebrates
PubMed: 12787742
DOI: 10.1016/s1286-4579(03)00097-2 -
Parasite (Paris, France) Dec 2010Lyme disease is a tick borne zoonotic infection, caused by Borrelia burgdorferi s.l. bacteria. For the transmission of the disease, the presence of ticks is a...
Lyme disease is a tick borne zoonotic infection, caused by Borrelia burgdorferi s.l. bacteria. For the transmission of the disease, the presence of ticks is a prerequisite. Lyme borreliosis mostly occurs in people and dogs, but it may occur in other animals. Ticks which carry B. burgdorferi s.l. in Serbia are of the Ixodes ricinus specis. In Serbia, Lyme disease was detected for the first time in the late '80-es. In dogs, clinical symptoms may occur even months after a tick bite, and include weakness, lymphadenopathy, fever, lameness, arthritis, etc. In our survey, we have observed tick and dog populations in the province of Vojvodina (northern part of Serbia). I. ricinus ticks were collected and examined for the presence of B. burgdorferi s.l. in several chosen locations. In addition, blood samples were collected from house dogs and pets from the same locations, and analyzed for the presence of antibodies specific for B. burgdorferi s.l. The results showed a mean infection of ticks of 22.12%, and a mean seroprevalence of Lyme disease in dogs of 25.81%. We conclude that in Vojvodina there is an actual risk of Lyme borreliosis for other animals and humans, because of the persistence of B. burgdorferi s.l. in both tick and dog populations.
Topics: Animals; Body Size; Borrelia Infections; Borrelia burgdorferi; Dog Diseases; Dogs; Female; Male; Prevalence; Serbia; Ticks
PubMed: 21275243
DOI: 10.1051/parasite/2010174357 -
PloS One 2022Borrelia burgdorferi is an important tickborne human pathogen comprising several strains based on nucleotide sequence of the outer surface protein C (ospC) gene....
Borrelia burgdorferi is an important tickborne human pathogen comprising several strains based on nucleotide sequence of the outer surface protein C (ospC) gene. Detection and characterization of different ospC genotypes is vital for research on B. burgdorferi and the risk it poses to humans. Here we present a novel, multiplex assay based on Luminex xMAP technology for the detection of B. burgdorferi ospC genotypes. The assay has five major steps: amplification of the ospC gene, hydrolyzation of surplus primers and nucleotides, incorporation of biotinylated nucleotides into the template DNA, hybridization to Luminex microspheres, and detection of fluorescent signals corresponding to each ospC genotype. We validated the protocol by comparing results obtained from our method against results from an established ospC genotyping method. This protocol can be used for the characterization of ospC genotypes in B. burgdorferi infected ticks, reservoir hosts, and/or clinical samples.
Topics: Antigens, Bacterial; Bacterial Outer Membrane Proteins; Borrelia burgdorferi; DNA Primers; Genotype; Humans; Technology
PubMed: 35648767
DOI: 10.1371/journal.pone.0269266 -
PloS One 2018Lyme disease is caused by spirochaetes of the Borrelia burgdorferi sensu lato genospecies. Complete genome assemblies are available for fewer than ten strains of... (Comparative Study)
Comparative Study
Lyme disease is caused by spirochaetes of the Borrelia burgdorferi sensu lato genospecies. Complete genome assemblies are available for fewer than ten strains of Borrelia burgdorferi sensu stricto, the primary cause of Lyme disease in North America. MM1 is a sensu stricto strain originally isolated in the midwestern United States. Aside from a small number of genes, the complete genome sequence of this strain has not been reported. Here we present the complete genome sequence of MM1 in relation to other sensu stricto strains and in terms of its Multi Locus Sequence Typing. Our results indicate that MM1 is a new sequence type which contains a conserved main chromosome and 15 plasmids. Our results include the first contiguous 28.5 kb assembly of lp28-8, a linear plasmid carrying the vls antigenic variation system, from a Borrelia burgdorferi sensu stricto strain.
Topics: Animals; Bacterial Typing Techniques; Borrelia burgdorferi; Borrelia burgdorferi Group; Chromosome Mapping; Comparative Genomic Hybridization; DNA, Bacterial; Genetic Variation; Genome, Bacterial; High-Throughput Nucleotide Sequencing; Humans; Lyme Disease; Multilocus Sequence Typing
PubMed: 29889842
DOI: 10.1371/journal.pone.0198135 -
Microbiology Spectrum Jun 2015Borrelia burgdorferi, the spirochetal agent of Lyme disease, is a zoonotic pathogen that is maintained in a natural cycle that typically involves mammalian reservoir...
Borrelia burgdorferi, the spirochetal agent of Lyme disease, is a zoonotic pathogen that is maintained in a natural cycle that typically involves mammalian reservoir hosts and a tick vector of the Ixodes species. During each stage of the enzootic cycle, B. burgdorferi is exposed to environments that differ in temperature, pH, small molecules, and most important, nutrient sources. B. burgdorferi has a highly restricted metabolic capacity because it does not contain a tricarboxylic acid cycle, oxidative phosphorylation, or any pathways for de novo biosynthesis of carbohydrates, amino acids, or lipids. Thus, B. burgdorferi relies solely on glycolysis for ATP production and is completely dependent on the transport of nutrients and cofactors from extracellular sources. Herein, pathways for carbohydrate uptake and utilization in B. burgdorferi are described. Regulation of these pathways during the different phases of the enzootic cycle is discussed. In addition, a model for differential control of nutrient flux through the glycolytic pathway as the spirochete transits through the enzootic cycle is presented.
Topics: Animals; Borrelia burgdorferi; Carbon; Disaccharides; Gene Expression Regulation, Bacterial; Glycolysis; Humans; Ixodes; Lyme Disease; Mammals; Zoonoses
PubMed: 26185064
DOI: 10.1128/microbiolspec.MBP-0011-2014 -
MBio Jun 2021Borrelia burgdorferi, the etiological agent of Lyme disease, persists in nature through an enzootic cycle consisting of a vertebrate host and an tick vector. The...
Borrelia burgdorferi, the etiological agent of Lyme disease, persists in nature through an enzootic cycle consisting of a vertebrate host and an tick vector. The sequence motifs modified by two well-characterized restriction/modification (R/M) loci of B. burgdorferi type strain B31 were recently described, but the methylation profiles of other Lyme disease bacteria have not been characterized. Here, the methylomes of B. burgdorferi type strain B31 and 7 clonal derivatives, along with B. burgdorferi N40, B. burgdorferi 297, B. burgdorferi CA-11, B. afzelii PKo, B. afzelii BO23, and B. garinii PBr, were defined through PacBio single-molecule real-time (SMRT) sequencing. This analysis revealed 9 novel sequence motifs methylated by the plasmid-encoded restriction/modification enzymes of these strains. Furthermore, while a previous analysis of B. burgdorferi B31 revealed an epigenetic impact of methylation on the global transcriptome, the current data contradict those findings; our analyses of wild-type B. burgdorferi B31 revealed no consistent differences in gene expression among isogenic derivatives lacking one or more restriction/modification enzymes. The principal causative agent of Lyme disease in humans in the United States is Borrelia burgdorferi, while B. burgdorferi, B. afzelii, and B. garinii, collectively members of the Borrelia burgdorferi species complex, cause Lyme disease in Europe and Asia. Two plasmid-encoded restriction/modification systems have been shown to limit the genetic transformation of B. burgdorferi type strain B31 with foreign DNA, but little is known about the restriction/modification systems of other Lyme disease bacteria. This paper describes the methylation motifs present on genomic DNAs of multiple B. burgdorferi, B. afzelii, and B. garinii strains. Contrary to a previous report, we did not find evidence for an epigenetic impact on gene expression by methylation. Knowledge of the motifs recognized and methylated by the restriction/modification enzymes of Lyme disease will facilitate molecular genetic investigations of these important human pathogens. Additionally, the similar motifs methylated by orthologous restriction/modification systems of Lyme disease bacteria and the presence of these motifs within recombinogenic loci suggest a biological role for these ubiquitous restriction/modification systems in horizontal gene transfer.
Topics: Animals; Borrelia burgdorferi; DNA, Bacterial; Epigenomics; Humans; Lyme Disease; Methylation; Nucleotide Motifs; Plasmids; Sequence Analysis, DNA
PubMed: 34156261
DOI: 10.1128/mBio.01288-21 -
Infection and Immunity Sep 2018responds to a variety of host-derived factors and appropriately alters its gene expression for adaptation under different host-specific conditions. We previously showed...
responds to a variety of host-derived factors and appropriately alters its gene expression for adaptation under different host-specific conditions. We previously showed that various levels of acetate, a short-chain fatty acid (SCFA), altered the protein profile of In this study, we determined the effects of other physiologically relevant SCFAs in the regulation of metabolic/virulence-associated proteins using mutant borrelial strains. No apparent increase in the synthesis of outer surface protein C (OspC) was noted when a carbon storage regulator A ( of , or ) mutant (mt) was propagated within dialysis membrane chambers implanted within rat peritoneal cavity, while the parental wild type (wt; B31-A3 strain) and -complemented strain (ct) had increased OspC with a reciprocal reduction in OspA levels. Growth rates of wt, mt, ct, 7D ( mutant lacking 7 amino acids at the C terminus), and 8S ( with site-specific changes altering its RNA-binding properties) borrelial strains were similar in the presence of acetate. Increased levels of propionate and butyrate reduced the growth rates of all strains tested, with mt and 8S exhibiting profound growth deficits at higher concentrations of propionate. Transcriptional levels of and were elevated on supplementation of SCFAs compared to those of untreated spirochetes. Immunoblot analysis revealed elevated levels of RpoS, OspC, and DbpA with increased levels of SCFAs. Physiological levels of SCFAs prevalent in select human and rodent fluids were synergistic with mammalian host temperature and pH to increase the levels of aforementioned proteins, which could impact the colonization of during the mammalian phase of infection.
Topics: Acetates; Animals; Antigens, Bacterial; Antigens, Surface; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Vaccines; Borrelia burgdorferi; Butyrates; Fatty Acids, Volatile; Humans; Hydrogen-Ion Concentration; Lipoproteins; Lyme Disease; Mutation; Propionates; Rats; Real-Time Polymerase Chain Reaction; Sigma Factor; Virulence
PubMed: 29891543
DOI: 10.1128/IAI.00217-18 -
Applied and Environmental Microbiology Nov 2015In North America, Lyme disease (LD) is a tick-borne zoonosis caused by the spirochete bacterium Borrelia burgdorferi sensu stricto, which is maintained by wildlife. Tick... (Review)
Review
In North America, Lyme disease (LD) is a tick-borne zoonosis caused by the spirochete bacterium Borrelia burgdorferi sensu stricto, which is maintained by wildlife. Tick vectors and bacteria are currently spreading into Canada and causing increasing numbers of cases of LD in humans and raising a pressing need for public health responses. There is no vaccine, and LD prevention depends on knowing who is at risk and informing them how to protect themselves from infection. Recently, it was found in the United States that some strains of B. burgdorferi sensu stricto cause severe disease, whereas others cause mild, self-limiting disease. While many strains occurring in the United States also occur in Canada, strains in some parts of Canada are different from those in the United States. We therefore recognize a need to identify which strains specific to Canada can cause severe disease and to characterize their geographic distribution to determine which Canadians are particularly at risk. In this review, we summarize the history of emergence of LD in North America, our current knowledge of B. burgdorferi sensu stricto diversity, its intriguing origins in the ecology and evolution of the bacterium, and its importance for the epidemiology and clinical and laboratory diagnosis of LD. We propose methods for investigating associations between B. burgdorferi sensu stricto diversity, ecology, and pathogenicity and for developing predictive tools to guide public health interventions. We also highlight the emergence of B. burgdorferi sensu stricto in Canada as a unique opportunity for exploring the evolutionary aspects of tick-borne pathogen emergence.
Topics: Borrelia burgdorferi; Canada; Communicable Diseases, Emerging; Humans; Lyme Disease; North America; Phylogeography
PubMed: 26296723
DOI: 10.1128/AEM.01671-15 -
BMC Genomics Feb 2017Bacteria from the genus Borrelia are known to harbor numerous linear and circular plasmids. We report here a comparative analysis of the nucleotide sequences of 236...
BACKGROUND
Bacteria from the genus Borrelia are known to harbor numerous linear and circular plasmids. We report here a comparative analysis of the nucleotide sequences of 236 plasmids present in fourteen independent isolates of the Lyme disease agent B. burgdorferi.
RESULTS
We have sequenced the genomes of 14 B. burgdorferi sensu stricto isolates that carry a total of 236 plasmids. These individual isolates carry between seven and 23 plasmids. Their chromosomes, the cp26 and cp32 circular plasmids, as well as the lp54 linear plasmid, are quite evolutionarily stable; however, the remaining plasmids have undergone numerous non-homologous and often duplicative recombination events. We identify 32 different putative plasmid compatibility types among the 236 plasmids, of which 15 are (usually) circular and 17 are linear. Because of past rearrangements, any given gene, even though it might be universally present in these isolates, is often found on different linear plasmid compatibility types in different isolates. For example, the arp gene and the vls cassette region are present on plasmids of four and five different compatibility types, respectively, in different isolates. A majority of the plasmid types have more than one organizationally different subtype, and the number of such variants ranges from one to eight among the 18 linear plasmid types. In spite of this substantial organizational diversity, the plasmids are not so variable that every isolate has a novel version of every plasmid (i.e., there appears to be a limited number of extant plasmid subtypes).
CONCLUSIONS
Although there have been many past recombination events, both homologous and nonhomologous, among the plasmids, particular organizational variants of these plasmids correlate with particular chromosomal genotypes, suggesting that there has not been rapid horizontal transfer of whole linear plasmids among B. burgdorferi lineages. We argue that plasmid rearrangements are essentially non-revertable and are present at a frequency of only about 0.65% that of single nucleotide changes, making rearrangement-derived novel junctions (mosaic boundaries) ideal phylogenetic markers in the study of B. burgdorferi population structure and plasmid evolution and exchange.
Topics: Borrelia burgdorferi; Chromosomes, Bacterial; Genetic Variation; Genome, Bacterial; Genomics; Lyme Disease; Phylogeny; Plasmids
PubMed: 28201991
DOI: 10.1186/s12864-017-3553-5 -
Infection and Immunity Sep 2015Borrelia burgdorferi, the etiologic agent of Lyme disease, produces a variety of proteins that promote survival and colonization in both the Ixodes species vector and...
Borrelia burgdorferi, the etiologic agent of Lyme disease, produces a variety of proteins that promote survival and colonization in both the Ixodes species vector and various mammalian hosts. We initially identified BB0744 (also known as p83/100) by screening for B. burgdorferi strain B31 proteins that bind to α1β1 integrin and hypothesized that, given the presence of a signal peptide, BB0744 may be a surface-exposed protein. In contrast to this expectation, localization studies suggested that BB0744 resides in the periplasm. Despite its subsurface location, we were interested in testing whether BB0744 is required for borrelial pathogenesis. To this end, a bb0744 deletion was isolated in a B. burgdorferi strain B31 infectious background, complemented, and queried for the role of BB0744 following experimental infection. A combination of bioluminescent imaging, cultivation of infected tissues, and quantitative PCR (qPCR) demonstrated that Δbb0744 mutant B. burgdorferi bacteria were attenuated in the ability to colonize heart tissue, as well as skin locations distal to the site of infection. Furthermore, qPCR indicated a significantly reduced spirochetal load in distal skin and joint tissue infected with Δbb0744 mutant B. burgdorferi. Complementation with bb0744 restored infectivity, indicating that the defect seen in Δbb0744 mutant B. burgdorferi was due to the loss of BB0744. Taken together, these results suggest that BB0744 is necessary for tissue tropism, particularly in heart tissue, alters the ability of B. burgdorferi to disseminate efficiently, or both. Additional studies are warranted to address the mechanism employed by BB0744 that alters the pathogenic potential of B. burgdorferi.
Topics: Adhesins, Bacterial; Animals; Borrelia burgdorferi; Disease Models, Animal; Female; Gene Knockdown Techniques; Immunoblotting; Luminescent Measurements; Lyme Disease; Mice; Mice, Inbred BALB C; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction
PubMed: 26150534
DOI: 10.1128/IAI.00828-15