scholarly journals Epigenomic Landscape of Lyme Disease Spirochetes Reveals Novel Motifs

mBio ◽  
2021 ◽  
Author(s):  
Jenny Wachter ◽  
Craig Martens ◽  
Kent Barbian ◽  
Ryan O. M. Rego ◽  
Patricia Rosa
Keyword(s):  
United States ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Type Strain ◽  
Species Complex ◽  
The United States ◽  
Content Type ◽  
Foreign Dna ◽  
Restriction Modification ◽  
Restriction Modification Systems

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 sensu lato 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 Borrelia bacteria.

scholarly journals DNA Methylation by Restriction Modification Systems Affects the Global Transcriptome Profile inBorrelia burgdorferi

2018 ◽  
Vol 200 (24) ◽  
Author(s):  
Timothy Casselli ◽  
Yvonne Tourand ◽  
Adam Scheidegger ◽  
William K. Arnold ◽  
Anna Proulx ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Gene Regulation ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Expression Profiles ◽  
Content Type ◽  
Foreign Dna ◽  
Restriction Modification ◽  
Restriction Modification Systems

ABSTRACTProkaryote restriction modification (RM) systems serve to protect bacteria from potentially detrimental foreign DNA. Recent evidence suggests that DNA methylation by the methyltransferase (MTase) components of RM systems can also have effects on transcriptome profiles. The type strain of the causative agent of Lyme disease,Borrelia burgdorferiB31, possesses two RM systems withN6-methyladenosine (m6A) MTase activity, which are encoded by thebbe02gene located on linear plasmid lp25 andbbq67on lp56. The specific recognition and/or methylation sequences had not been identified for either of theseB. burgdorferiMTases, and it was not previously known whether these RM systems influence transcript levels. In the current study, single-molecule real-time sequencing was utilized to map genome-wide m6A sites and to identify consensus modified motifs in wild-typeB. burgdorferias well as MTase mutants lacking either thebbe02gene alone or bothbbe02andbbq67genes. Four novel conserved m6A motifs were identified and were fully attributable to the presence of specific MTases. Whole-genome transcriptome changes were observed in conjunction with the loss of MTase enzymes, indicating that DNA methylation by the RM systems has effects on gene expression. Genes with altered transcription in MTase mutants include those involved in vertebrate host colonization (e.g.,rpoSregulon) and acquisition by/transmission from the tick vector (e.g.,rrp1andpdeB). The results of this study provide a comprehensive view of the DNA methylation pattern inB. burgdorferi, and the accompanying gene expression profiles add to the emerging body of research on RM systems and gene regulation in bacteria.IMPORTANCELyme disease is the most prevalent vector-borne disease in North America and is classified by the Centers for Disease Control and Prevention (CDC) as an emerging infectious disease with an expanding geographical area of occurrence. Previous studies have shown that the causative bacterium,Borrelia burgdorferi, methylates its genome using restriction modification systems that enable the distinction from foreign DNA. Although much research has focused on the regulation of gene expression inB. burgdorferi, the effect of DNA methylation on gene regulation has not been evaluated. The current study characterizes the patterns of DNA methylation by restriction modification systems inB. burgdorferiand evaluates the resulting effects on gene regulation in this important pathogen.

scholarly journals The Past, Present, and (Possible) Future of Serologic Testing for Lyme Disease

2016 ◽  
Vol 54 (5) ◽  
pp. 1191-1196 ◽  
Author(s):  
Elitza S. Theel
Keyword(s):  
United States ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Metabolic Profiling ◽  
Historical Perspective ◽  
The United States ◽  
Performance Characteristics ◽  
Content Type ◽  
The Past ◽  
Testing Algorithm

Lyme disease prevails as the most commonly transmitted tick-borne infection in the United States, and serologic evaluation for antibodies toBorrelia burgdorferiremains the recommended modality for diagnosis. This review presents a brief historical perspective on the evolution of serologic assays for Lyme disease and provides a summary of the performance characteristics for the currently recommended two-tiered testing algorithm (TTTA). Additionally, a recently proposed alternative to the traditional TTTA is discussed, and novel methodologies, including immuno-PCR and metabolic profiling for Lyme disease, are outlined.

scholarly journals DNA Methylation by Restriction Modification Systems Affects the Global Transcriptome Profile inBorrelia burgdorferi

2018 ◽  
Author(s):  
Timothy Casselli ◽  
Yvonne Tourand ◽  
Adam Scheidegger ◽  
William K. Arnold ◽  
Anna Proulx ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Gene Regulation ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Expression Profiles ◽  
Geographical Area ◽  
Foreign Dna ◽  
Restriction Modification ◽  
Restriction Modification Systems

ABSTRACTProkaryote restriction modification (RM) systems serve to protect bacteria from potentially detrimental foreign DNA. Recent evidence suggests that DNA methylation by the methyltransferase (MTase) components of RM systems can also have effects on transcriptome profiles. The causative agent of Lyme disease,Borrelia burgdorferi, encodes two RM systems with N6-Methyladenosine (m6A) MTase activity. The specific recognition and/or methylation sequences have not been identified for eitherB. burgdorferiMTase, and it is not currently known whether these RM systems influence transcriptome profiles. In the current study, Single Molecule Real Time sequencing was utilized to map genome-wide m6A sites, and to identify consensus modified motifs in wild-typeB. burgdorferias well as isogenic MTase mutants. Four conserved m6A motifs were identified, and were fully attributable to the presence of specific MTases. Whole-genome transcriptome changes were observed in conjunction with the loss of MTase enzymes, indicating that DNA methylation by RM systems has effects on gene expression inB. burgdorferi. The results of this study provide a comprehensive view of the DNA methylation pattern inB. burgdorferi, and the accompanying gene expression profiles add to the emerging body of research on RM systems and gene regulation in bacteria.IMPORTANCELyme disease is the most prevalent vector-borne disease in North America, and is classified by the Centers for Disease Control and Prevention (CDC) as an emerging infectious disease with an expanding geographical area of occurrence. Previous studies have shown that the causative bacterium,Borrelia burgdorferi, methylates its genome using restriction modification systems that allow for the distinction of self from foreign DNA. Although much research has focused on the regulation of gene expression inB. burgdorferi, the effects of DNA methylation on gene regulation has not been evaluated. The current study characterizes the patterns of DNA methylation by restriction modification systems inB. burgdorferi, and evaluates the resulting effects on gene regulation in this important pathogen.

scholarly journals Investigation of Genotypes of Borrelia burgdorferi in Ixodes scapularis Ticks Collected during Surveillance in Canada

2011 ◽  
Vol 77 (10) ◽  
pp. 3244-3254 ◽  
Author(s):  
N. H. Ogden ◽  
G. Margos ◽  
D. M. Aanensen ◽  
M. A. Drebot ◽  
E. J. Feil ◽  
...  
Keyword(s):  
United States ◽  
Genetic Diversity ◽  
North America ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Diagnostic Tests ◽  
Ixodes Scapularis ◽  
The United States ◽  
Borrelia Miyamotoi ◽  
Content Type

ABSTRACTThe genetic diversity ofBorrelia burgdorferisensu stricto, the agent of Lyme disease in North America, has consequences for the performance of serological diagnostic tests and disease severity. To investigateB. burgdorferidiversity in Canada, where Lyme disease is emerging, bacterial DNA in 309 infected adultIxodes scapularisticks collected in surveillance was characterized by multilocus sequence typing (MLST) and analysis of outer surface protein C gene (ospC) alleles. Six ticks carriedBorrelia miyamotoi, and one tick carried the novel speciesBorrelia kurtenbachii. 142 ticks carriedB. burgdorferisequence types (STs) previously described from the United States. Fifty-eight ticks carriedB. burgdorferiof 1 of 19 novel or undescribed STs, which were single-, double-, or triple-locus variants of STs first described in the United States. Clonal complexes with founder STs from the United States were identified. SeventeenospCalleles were identified in 309B. burgdorferi-infected ticks. Positive and negative associations in the occurrence of different alleles in the same tick supported a hypothesis of multiple-niche polymorphism forB. burgdorferiin North America. Geographic analysis of STs andospCalleles were consistent with south-to-north dispersion of infected ticks from U.S. sources on migratory birds. These observations suggest that the genetic diversity ofB. burgdorferiin eastern and central Canada corresponds to that in the United States, but there was evidence for founder events skewing the diversity in emerging tick populations. Further studies are needed to investigate the significance of these observations for the performance of diagnostic tests and clinical presentation of Lyme disease in Canada.

scholarly journals Mycobacterium talmoniae, a Potential Pulmonary Pathogen Isolated from Multiple Patients with Bronchiectasis in the United States, Including the First Case of Clinical Disease in a Patient with Cystic Fibrosis

2018 ◽  
Vol 57 (2) ◽  
Author(s):  
Ravikiran Vasireddy ◽  
Sruthi Vasireddy ◽  
Barbara A. Brown-Elliott ◽  
Alexander L. Greninger ◽  
Rebecca M. Davidson ◽  
...  
Keyword(s):  
United States ◽  
Cystic Fibrosis ◽  
16S Rrna ◽  
Type Strain ◽  
Gene Sequencing ◽  
The United States ◽  
Average Nucleotide Identity ◽  
Content Type ◽  
First Case ◽  
Multiple Patients

ABSTRACTWe characterize three respiratory isolates of the recently described speciesMycobacterium talmoniaerecovered in Texas, Louisiana, and Massachusetts, including the first case of disease in a patient with underlying cystic fibrosis. The three isolates had a 100% match toM. talmoniaeNE-TNMC-100812Tby complete 16S rRNA,rpoBregion V, andhsp65 gene sequencing. Core genomic comparisons between one isolate and the type strain revealed an average nucleotide identity of 99.8%. The isolates were susceptible to clarithromycin, amikacin, and rifabutin, while resistance was observed for tetracyclines, ciprofloxacin, and linezolid.M. talmoniaeshould be added to the list of potential pulmonary pathogens, including in the setting of cystic fibrosis.

scholarly journals Veterinary Fusarioses within the United States

2016 ◽  
Vol 54 (11) ◽  
pp. 2813-2819 ◽  
Author(s):  
Kerry O'Donnell ◽  
Deanna A. Sutton ◽  
Nathan Wiederhold ◽  
Vincent A. R. G. Robert ◽  
Pedro W. Crous ◽  
...  
Keyword(s):  
United States ◽  
Dna Sequence ◽  
Species Complex ◽  
Sequence Data ◽  
Phylogenetic Analyses ◽  
Distinct Species ◽  
The United States ◽  
Content Type ◽  
Dna Sequence Data ◽  
Species Complexes

Multilocus DNA sequence data were used to assess the genetic diversity and evolutionary relationships of 67Fusariumstrains from veterinary sources, most of which were from the United States. Molecular phylogenetic analyses revealed that the strains comprised 23 phylogenetically distinct species, all but two of which were previously known to infect humans, distributed among eight species complexes. The majority of the veterinary isolates (47/67 = 70.1%) were nested within theFusarium solanispecies complex (FSSC), and these included 8 phylospecies and 33 unique 3-locus sequence types (STs). Three of the FSSC species (Fusarium falciforme,Fusarium keratoplasticum, andFusariumsp. FSSC 12) accounted for four-fifths of the veterinary strains (38/47) and STs (27/33) within this clade. Most of theF. falciformestrains (12/15) were recovered from equine keratitis infections; however, strains ofF. keratoplasticumandFusariumsp. FSSC 12 were mostly (25/27) isolated from marine vertebrates and invertebrates. Our sampling suggests that theFusarium incarnatum-equisetispecies complex (FIESC), with eight mycoses-associated species, may represent the second most important clade of veterinary relevance withinFusarium. Six of the multilocus STs within the FSSC (3+4-eee, 1-b, 12-a, 12-b, 12-f, and 12-h) and one each within the FIESC (1-a) and theFusarium oxysporumspecies complex (ST-33) were widespread geographically, including three STs with transoceanic disjunctions. In conclusion, fusaria associated with veterinary mycoses are phylogenetically diverse and typically can only be identified to the species level using DNA sequence data from portions of one or more informative genes.

scholarly journals Comparative Genomics of Vancomycin-Resistant Staphylococcus aureus Strains and Their Positions within the Clade Most Commonly Associated with Methicillin-Resistant S. aureus Hospital-Acquired Infection in the United States

mBio ◽  
2012 ◽  
Vol 3 (3) ◽  
Author(s):  
Veronica N. Kos ◽  
Christopher A. Desjardins ◽  
Allison Griggs ◽  
Gustavo Cerqueira ◽  
Andries Van Tonder ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
The United States ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Infection ◽  
Vancomycin Resistant ◽  
Foreign Dna ◽  
Mrsa Strains ◽  
Hospital Acquired

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) strains are leading causes of hospital-acquired infections in the United States, and clonal cluster 5 (CC5) is the predominant lineage responsible for these infections. Since 2002, there have been 12 cases of vancomycin-resistantS. aureus(VRSA) infection in the United States—all CC5 strains. To understand this genetic background and what distinguishes it from other lineages, we generated and analyzed high-quality draft genome sequences for all available VRSA strains. Sequence comparisons show unambiguously that each strain independently acquired Tn1546and that all VRSA strains last shared a common ancestor over 50 years ago, well before the occurrence of vancomycin resistance in this species. In contrast to existing hypotheses on what predisposes this lineage to acquire Tn1546, the barrier posed by restriction systems appears to be intact in most VRSA strains. However, VRSA (and other CC5) strains were found to possess a constellation of traits that appears to be optimized for proliferation in precisely the types of polymicrobic infection where transfer could occur. They lack a bacteriocin operon that would be predicted to limit the occurrence of non-CC5 strains in mixed infection and harbor a cluster of unique superantigens and lipoproteins to confound host immunity. A frameshift indprA, which in other microbes influences uptake of foreign DNA, may also make this lineage conducive to foreign DNA acquisition.IMPORTANCEInvasive methicillin-resistantStaphylococcus aureus(MRSA) infection now ranks among the leading causes of death in the United States. Vancomycin is a key last-line bactericidal drug for treating these infections. However, since 2002, vancomycin resistance has entered this species. Of the now 12 cases of vancomycin-resistantS. aureus(VRSA), each was believed to represent a new acquisition of the vancomycin-resistant transposon Tn1546from enterococcal donors. All acquisitions of Tn1546so far have occurred in MRSA strains of the clonal cluster 5 genetic background, the most common hospital lineage causing hospital-acquired MRSA infection. To understand the nature of these strains, we determined and examined the nucleotide sequences of the genomes of all available VRSA. Genome comparison identified candidate features that position strains of this lineage well for acquiring resistance to antibiotics in mixed infection.

scholarly journals Mycobacterium arupense, Mycobacterium heraklionense, and a Newly Proposed Species, “Mycobacterium virginiense” sp. nov., but Not Mycobacterium nonchromogenicum, as Species of the Mycobacterium terrae Complex Causing Tenosynovitis and Osteomyelitis

2016 ◽  
Vol 54 (5) ◽  
pp. 1340-1351 ◽  
Author(s):  
Ravikiran Vasireddy ◽  
Sruthi Vasireddy ◽  
Barbara A. Brown-Elliott ◽  
Nancy L. Wengenack ◽  
Uzoamaka A. Eke ◽  
...  
Keyword(s):  
United States ◽  
16S Rrna ◽  
Species Identification ◽  
Type Strain ◽  
Molecular Taxonomy ◽  
The United States ◽  
Undescribed Species ◽  
Content Type ◽  
Sequence Identity ◽  
As Species

Mycobacterium terraecomplex has been recognized as a cause of tenosynovitis, withM. terraeandMycobacterium nonchromogenicumreported as the primary etiologic pathogens. The molecular taxonomy of theM. terraecomplex causing tenosynovitis has not been established despite approximately 50 previously reported cases. We evaluated 26 isolates of theM. terraecomplex associated with tenosynovitis or osteomyelitis recovered between 1984 and 2014 from 13 states, including 5 isolates reported in 1991 asM. nonchromogenicumby nonmolecular methods. The isolates belonged to three validated species, one new proposed species, and two novel related strains. The majority of isolates (20/26, or 77%) belonged to two recently described species:Mycobacterium arupense(10 isolates, or 38%) andMycobacterium heraklionense(10 isolates, or 38%). Three isolates (12%) had 100% sequence identity to each other by 16S rRNA and 99.3 to 100% identity byrpoBgene region V sequencing and represent a previously undescribed species within theM. terraecomplex. There were no isolates ofM. terraeorM. nonchromogenicum, including among the five isolates reported in 1991. The 26 isolates were susceptible to clarithromycin (100%), rifabutin (100%), ethambutol (92%), and sulfamethoxazole or trimethoprim-sulfamethoxazole (70%). The current study suggests thatM. arupense,M. heraklionense, and a newly proposed species (“M. virginiense” sp. nov.; proposed type strain MO-233 [DSM 100883, CIP 110918]) within theM. terraecomplex are the major causes of tenosynovitis and osteomyelitis in the United States, with little change over 20 years. Species identification within this complex requires sequencing methods.

scholarly journals Antibodies to Borrelia burgdorferi OspA, OspC, OspF, and C6 Antigens as Markers for Early and Late Infection in Dogs

2012 ◽  
Vol 19 (4) ◽  
pp. 527-535 ◽  
Author(s):  
Bettina Wagner ◽  
Heather Freer ◽  
Alicia Rollins ◽  
David Garcia-Tapia ◽  
Hollis N. Erb ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
The United States ◽  
Sensu Stricto ◽  
Antibody Responses ◽  
Surface Proteins ◽  
Early Infection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Content Type ◽  
Antibody Levels

ABSTRACTLyme disease in the United States is caused byBorrelia burgdorferisensu stricto, which is transmitted to mammals by infected ticks.Borreliaspirochetes differentially express immunogenic outer surface proteins (Osp). Our aim was to evaluate antibody responses to Osp antigens to aid the diagnosis of early infection and the management of Lyme disease. We analyzed antibody responses during the first 3 months after the experimental infection of dogs using a novel multiplex assay. Results were compared to those obtained with two commercial assays detecting C6 antigen. Multiplex analysis identified antibodies to OspC and C6 as early as 3 weeks postinfection (p.i.) and those to OspF by 5 weeks p.i. Antibodies to C6 and OspF increased throughout the study, while antibodies to OspC peaked between 7 and 11 weeks p.i. and declined thereafter. A short-term antibody response to OspA was observed in 3/8 experimentally infected dogs on day 21 p.i. Quant C6 enzyme-linked immunosorbent assay (ELISA) results matched multiplex results during the first 7 weeks p.i.; however, antibody levels subsequently declined by up to 29%. Immune responses then were analyzed in sera from 125 client-owned dogs and revealed high agreement between antibodies to OspF and C6 as robust markers for infection. Results from canine patient sera supported that OspC is an early infection marker and antibodies to OspC decline over time. The onset and decline of antibody responses toB. burgdorferiOsp antigens and C6 reflect their differential expression during infection. They provide valuable tools to determine the stage of infection, treatment outcomes, and vaccination status in dogs.

scholarly journals Completed Genome Sequences of Borrelia burgdorferiSensu Stricto B31(NRZ) and Closely Related Patient Isolates from Europe

2017 ◽  
Vol 5 (28) ◽  
Author(s):  
Gabriele Margos ◽  
Sabrina Hepner ◽  
Christoph Mang ◽  
Andreas Sing ◽  
Bernhard Liebl ◽  
...  
Keyword(s):  
United States ◽  
Borrelia Burgdorferi ◽  
Lyme Borreliosis ◽  
Causative Agent ◽  
Erythema Migrans ◽  
The United States ◽  
Sensu Stricto ◽  
Genome Sequences ◽  
Content Type

ABSTRACT Borrelia burgdorferi sensu stricto is a causative agent of human Lyme borreliosis in the United States and Europe. We report here the completed genome sequences of strain B31 isolated from a tick in the United States and two closely related strains from Europe, PAli and PAbe, which were isolated from patients with erythema migrans and neuroborreliosis, respectively.

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