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FEBS Letters Aug 2020Borreliosis (Lyme disease) is a spirochetal disease caused by the species complex of Borrelia burgdorferi transmitted by Ixodes spp. ticks. Recorded to be the most... (Review)
Review
Borreliosis (Lyme disease) is a spirochetal disease caused by the species complex of Borrelia burgdorferi transmitted by Ixodes spp. ticks. Recorded to be the most common tick-borne disease in the world, the last two decades have seen an increase in disease incidence and distribution, exceeding 360 000 cases in Europe alone. If untreated, infection may cause skin symptoms, arthritis, and neurological or cardiac complications. Borrelia spirochetes have developed strategies to evade the mammalian host immune system. These include the complement system, which is an important first-line defense mechanism against invading microbes. To evade the complement, spirochetes bind soluble complement regulators factor H (FH), factor H-like protein, and C4bp to their outer surfaces. B. burgdorferi spirochetes can inhibit the classical pathway of complement by the outer surface protein (Osp) BBK32, which blocks the activation of the C1 complex, composed of C1q, C1r, and C1s. The FH-binding proteins of borreliae include Osps OspE, CspA, and CspZ. Following repeated infections, antibodies against these proteins develop and may provide functional immunity against borreliosis. This review discusses critical immune evasion strategies, focusing on complement evasion by borreliae.
Topics: Animals; Antibodies, Bacterial; Bacterial Proteins; Borrelia burgdorferi; Complement System Proteins; Humans; Immune Evasion; Lyme Disease
PubMed: 32748966
DOI: 10.1002/1873-3468.13894 -
Microbes and Infection Apr 2006We outline in this review how Borrelia burgdorferi, the causative agent of Lyme disease, moves from the tick to the vertebrate host, and what molecules are potentially... (Review)
Review
We outline in this review how Borrelia burgdorferi, the causative agent of Lyme disease, moves from the tick to the vertebrate host, and what molecules are potentially involved in this challenging commute. The survival strategies utilized by the spirochete during transmission and the initial stages of infection are discussed.
Topics: Animals; Arachnid Vectors; Bacterial Proteins; Borrelia burgdorferi; Gene Expression Regulation, Bacterial; Humans; Ixodes; Lyme Disease
PubMed: 16698304
DOI: 10.1016/j.micinf.2005.12.022 -
Journal of Bacteriology Jan 2023Borrelia burgdorferi, the spirochete agent of Lyme disease, has evolved within a consistent infectious cycle between tick and vertebrate hosts. The transmission of the...
Borrelia burgdorferi, the spirochete agent of Lyme disease, has evolved within a consistent infectious cycle between tick and vertebrate hosts. The transmission of the pathogen from tick to vertebrate is characterized by rapid replication and a change in the outer surface protein profile. EbfC, a highly conserved nucleoid-associated protein, binds throughout the borrelial genome, affecting expression of many genes, including the Erp outer surface proteins. In B. burgdorferi, like many other bacterial species, is cotranscribed with , an essential component of the DNA polymerase III holoenzyme, which facilitates chromosomal replication. The expression of the operon is tied to the spirochete's replication rate, but the underlying mechanism for this connection was unknown. In this work, we provide evidence that the expression of is controlled by direct interactions of DnaA, the chromosomal replication initiator, and EbfC at the unusually long 5' untranslated region (UTR). Both proteins bind to the 5' UTR DNA, with EbfC also binding to the RNA. The DNA binding of DnaA to this region was similarly impacted by ATP and ADP. studies characterized DnaA as an activator of and EbfC as an antiactivator. We further found evidence that DnaA may regulate other genes essential for replication. The dual life cycle of Borrelia burgdorferi, the causative agent of Lyme disease, is characterized by periods of rapid and slowed replication. The expression patterns of many of the spirochete's virulence factors are impacted by these changes in replication rates. The connection between replication and virulence can be understood at the operon. DnaX is an essential component of the DNA polymerase III holoenzyme, which replicates the chromosome. EbfC is a nucleoid-associated protein that regulates the infection-associated outer surface Erp proteins, as well as other transcripts. The expression of is tied to replication rate, which we demonstrate is mediated by DnaA, the master chromosomal initiator protein and transcription factor, and EbfC.
Topics: Animals; Borrelia burgdorferi; Bacterial Proteins; DNA Polymerase III; Lyme Disease; Operon; Ticks; Membrane Proteins; Gene Expression Regulation, Bacterial
PubMed: 36533911
DOI: 10.1128/jb.00396-22 -
Revue Scientifique Et Technique... Apr 2000Lyme borreliosis, the most common vector-borne disease in the northern hemisphere, is caused by bacteria belonging to the Borrelia burgdorferi complex. The disease is... (Review)
Review
Lyme borreliosis, the most common vector-borne disease in the northern hemisphere, is caused by bacteria belonging to the Borrelia burgdorferi complex. The disease is multisystemic, affecting mainly the skin, nervous system, heart and joints. In Europe, the vector of the disease is the tick Ixodes ricinus, whereas in the United States of America, two primary tick vectors exist, namely: I. scapularis in the north-eastern and mid-western regions and I. pacificus on the west coast. Several species of small and medium-sized mammals and ground-feeding birds serve as reservoirs for the bacteria in endemic areas. The prognosis for patients with Lyme borreliosis is excellent, particularly when diagnosed and treated early in the course of infection. Prevention of Lyme borreliosis can be achieved using two approaches, either prevention of infection by immunisation, or prevention of tick bites through avoidance, personal protection and tick control.
Topics: Animals; Arachnid Vectors; Borrelia burgdorferi; Disease Reservoirs; Humans; Ixodes; Lyme Disease; Prognosis; Zoonoses
PubMed: 11189709
DOI: 10.20506/rst.19.1.1205 -
Journal of the American Veterinary... Nov 2003Despite more than 25 years' experience with Lyme borreliosis, much remains to be learned about this complex zoonosis. Practicing veterinarians, particularly those in the... (Review)
Review
Despite more than 25 years' experience with Lyme borreliosis, much remains to be learned about this complex zoonosis. Practicing veterinarians, particularly those in the northeastern and upper midwestern states, where Lyme borreliosis is highly endemic, should be familiar with the ecologic features and typical clinical signs of Lyme borreliosis. Interpretation of signs and serologic test results should be made with consideration of the regional prevalence of Lyme borreliosis and the animal's opportunity for exposure to infected Ixodes spp. The availability of recently marketed topical acaracides is a valuable adjunctive measure in prevention of Lyme borreliosis. A maximally effective prevention strategy should include consideration of environmental modification, activity restrictions, routine examinations for ticks, prompt removal of attached ticks, and vaccination. Technologic advances, such as the C6 EIA and the Osp A recombinant vaccine, offer the promise of additional tools for the clinical management and prevention of this tick-borne zoonosis.
Topics: Animals; Animals, Domestic; Borrelia burgdorferi; Dogs; Horses; Humans; Ixodes; Lyme Disease; Public Health; Tick Control; United States; Zoonoses
PubMed: 14621212
DOI: 10.2460/javma.2003.223.1261 -
Frontiers in Cellular and Infection... 2015
Topics: Animals; Arachnid Vectors; Bacterial Vaccines; Borrelia burgdorferi; Humans; Lyme Disease; Ticks
PubMed: 25883907
DOI: 10.3389/fcimb.2015.00027 -
Trends in Microbiology Nov 2020The complement system is an ancient arm of the innate immune system that plays important roles in pathogen recognition and elimination. Upon activation by microbes,... (Review)
Review
The complement system is an ancient arm of the innate immune system that plays important roles in pathogen recognition and elimination. Upon activation by microbes, complement opsonizes bacterial surfaces, recruits professional phagocytes, and causes bacteriolysis. Borreliella species are spirochetal bacteria that are transmitted to vertebrate hosts via infected Ixodes ticks and are the etiologic agents of Lyme disease. Pathogens that traffic in blood and other body fluids, like Borreliella, have evolved means to evade complement. Lyme disease spirochetes interfere with complement by producing a small arsenal of outer-surface lipoproteins that bind host complement components and manipulate their native activities. Here we review the current landscape of complement evasion by Lyme disease spirochetes and provide an update on recent discoveries.
Topics: Animals; Borrelia burgdorferi; Complement System Proteins; Humans; Immune Evasion; Immunity, Innate; Ixodes; Lyme Disease
PubMed: 32482556
DOI: 10.1016/j.tim.2020.05.004 -
Microbiology Spectrum Jul 2019Periplasmic flagella are complex nanomachines responsible for distinctive morphology and motility of spirochetes. Although bacterial flagella have been extensively... (Review)
Review
Periplasmic flagella are complex nanomachines responsible for distinctive morphology and motility of spirochetes. Although bacterial flagella have been extensively studied for several decades in the model systems and , our understanding of periplasmic flagella in many disease-causing spirochetes remains incomplete. Recent advances, including molecular genetics, biochemistry, structural biology, and cryo-electron tomography, have greatly increased our understanding of structure and function of periplasmic flagella. In this chapter, we summarize some of the recent findings that provide new insights into the structure, assembly, and function of periplasmic flagella.
Topics: Bacterial Proteins; Borrelia burgdorferi; Escherichia coli; Flagella; Periplasm; Salmonella enterica
PubMed: 31373267
DOI: 10.1128/microbiolspec.PSIB-0030-2019 -
Trends in Genetics : TIG Apr 2015Population genomic studies have the potential to address many unresolved questions about microbial pathogens by facilitating the identification of genes underlying... (Review)
Review
Population genomic studies have the potential to address many unresolved questions about microbial pathogens by facilitating the identification of genes underlying ecologically important traits, such as novel virulence factors and adaptations to humans or other host species. Additionally, this framework improves estimations of population demography and evolutionary history to accurately reconstruct recent epidemics and identify the molecular and environmental factors that resulted in the outbreak. The Lyme disease bacterium, Borrelia burgdorferi, exemplifies the power and promise of the application of population genomics to microbial pathogens. We discuss here the future of evolutionary studies in B. burgdorferi, focusing on the primary evolutionary forces of horizontal gene transfer, natural selection, and migration, as investigations transition from analyses of single genes to genomes.
Topics: Borrelia burgdorferi; Evolution, Molecular; Genetics, Population; Genomics; Humans; Lyme Disease; Phylogeny; Phylogeography; Research; Selection, Genetic
PubMed: 25765920
DOI: 10.1016/j.tig.2015.02.006 -
Environmental Microbiology Oct 2017Infections with tick-transmitted Borreliella (Borrelia) burgdorferi, the cause of Lyme disease, represent an increasingly large public health problem in North America... (Review)
Review
Infections with tick-transmitted Borreliella (Borrelia) burgdorferi, the cause of Lyme disease, represent an increasingly large public health problem in North America and Europe. The ability of these spirochetes to maintain themselves for extended periods of time in their tick vectors and vertebrate reservoirs is crucial for continuance of the enzootic cycle as well as for the increasing exposure of humans to them. The stringent response mediated by the alarmone (p)ppGpp has been determined to be a master regulator in B. burgdorferi. It modulates the expression of identified and unidentified open reading frames needed to deal with and overcome the many nutritional stresses and other challenges faced by the spirochete in ticks and animal reservoirs. The metabolic and morphologic changes resulting from activation of the stringent response in B. burgdorferi may also be involved in the recently described non-genetic phenotypic phenomenon of tolerance to otherwise lethal doses of antimicrobials and to other antimicrobial activities. It may thus constitute a linchpin in multiple aspects of infections with Lyme disease borrelia, providing a link between the micro-ecological challenges of its enzootic life-cycle and long-term residence in the tissues of its animal reservoirs, with the evolutionary side effect of potential persistence in incidental human hosts.
Topics: Animals; Anti-Bacterial Agents; Borrelia burgdorferi; Drug Resistance, Multiple, Bacterial; Europe; Humans; Ixodes; Life Cycle Stages; Lyme Disease; Mice; North America
PubMed: 28836724
DOI: 10.1111/1462-2920.13897