scholarly journals Comparative Genome Analysis of the Pathogenic Spirochetes Borrelia burgdorferi and Treponema pallidum

2000 ◽  
Vol 68 (3) ◽  
pp. 1633-1648 ◽  
Author(s):  
G. Subramanian ◽  
Eugene V. Koonin ◽  
L. Aravind
Keyword(s):  
Comparative Analysis ◽  
Borrelia Burgdorferi ◽  
Profile Analysis ◽  
Treponema Pallidum ◽  
Evolutionary Process ◽  
Specific Protein ◽  
Genome Replication ◽  
Ancestral State ◽  
Sequence Profile ◽  
Gene Sets

ABSTRACT A comparative analysis of the predicted protein sequences encoded in the complete genomes of Borrelia burgdorferi andTreponema pallidum provides a number of insights into evolutionary trends and adaptive strategies of the two spirochetes. A measure of orthologous relationships between gene sets, termed the orthology coefficient (OC), was developed. The overall OC value for the gene sets of the two spirochetes is about 0.43, which means that less than one-half of the genes show readily detectable orthologous relationships. This emphasizes significant divergence between the two spirochetes, apparently driven by different biological niches. Different functional categories of proteins as well as different protein families show a broad distribution of OC values, from near 1 (a perfect, one-to-one correspondence) to near 0. The proteins involved in core biological functions, such as genome replication and expression, typically show high OC values. In contrast, marked variability is seen among proteins that are involved in specific processes, such as nutrient transport, metabolism, gene-specific transcription regulation, signal transduction, and host response. Differences in the gene complements encoded in the two spirochete genomes suggest active adaptive evolution for their distinct niches. Comparative analysis of the spirochete genomes produced evidence of gene exchanges with other bacteria, archaea, and eukaryotic hosts that seem to have occurred at different points in the evolution of the spirochetes. Examples are presented of the use of sequence profile analysis to predict proteins that are likely to play a role in pathogenesis, including secreted proteins that contain specific protein-protein interaction domains, such as von Willebrand A, YWTD, TPR, and PR1, some of which hitherto have been reported only in eukaryotes. We tentatively reconstruct the likely evolutionary process that has led to the divergence of the two spirochete lineages; this reconstruction seems to point to an ancestral state resembling the symbiotic spirochetes found in insect guts.

scholarly journals Molecular Factors and Biochemical Pathways Induced by Febrile Temperature in Intraerythrocytic Plasmodium falciparum Parasites

2007 ◽  
Vol 75 (4) ◽  
pp. 2012-2025 ◽  
Author(s):  
Miranda S. M. Oakley ◽  
Sanjai Kumar ◽  
Vivek Anantharaman ◽  
Hong Zheng ◽  
Babita Mahajan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Elevated Temperature ◽  
Profile Analysis ◽  
Expression Profiles ◽  
Febrile Illness ◽  
Dependent Manner ◽  
Sequence Profile ◽  
Host Cell Membrane ◽  
Altered Expression ◽  
Parasite Survival

ABSTRACT Intermittent episodes of febrile illness are the most benign and recognized symptom of infection with malaria parasites, although the effects on parasite survival and virulence remain unclear. In this study, we identified the molecular factors altered in response to febrile temperature by measuring differential expression levels of individual genes using high-density oligonucleotide microarray technology and by performing biological assays in asexual-stage Plasmodium falciparum parasite cultures incubated at 37°C and 41°C (an elevated temperature that is equivalent to malaria-induced febrile illness in the host). Elevated temperature had a profound influence on expression of individual genes; 336 of approximately 5,300 genes (6.3% of the genome) had altered expression profiles. Of these, 163 genes (49%) were upregulated by twofold or greater, and 173 genes (51%) were downregulated by twofold or greater. In-depth sensitive sequence profile analysis revealed that febrile temperature-induced responses caused significant alterations in the major parasite biologic networks and pathways and that these changes are well coordinated and intricately linked. One of the most notable transcriptional changes occurs in genes encoding proteins containing the predicted Pexel motifs that are exported into the host cytoplasm or inserted into the host cell membrane and are likely to be associated with erythrocyte remodeling and parasite sequestration functions. Using our sensitive computational analysis, we were also able to assign biochemical or biologic functional predictions for at least 100 distinct genes previously annotated as “hypothetical.” We find that cultivation of P. falciparum parasites at 41°C leads to parasite death in a time-dependent manner. The presence of the “crisis forms” and the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling-positive parasites following heat treatment strongly support the notion that an apoptosis-like cell death mechanism might be induced in response to febrile temperatures. These studies enhance the possibility of designing vaccines and drugs on the basis of disruption in molecules and pathways of parasite survival and virulence activated in response to febrile temperatures.

Culture-Confirmed Reinfection of a Person with Different Strains of Borrelia burgdorferi Sensu Stricto

1998 ◽  
Vol 36 (4) ◽  
pp. 1015-1019 ◽  
Author(s):  
William T. Golde ◽  
Barbara Robinson-Dunn ◽  
Mary Grace Stobierski ◽  
Daniel Dykhuizen ◽  
Ing-Nang Wang ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Profile Analysis ◽  
Protein Profile ◽  
Erythema Migrans ◽  
Diagnostic Testing ◽  
Serum Antibody ◽  
Surface Protein ◽  
Punch Biopsy ◽  
Skin Punch Biopsy ◽  
Different Strains

In recent years, the utility of serum-based diagnostic testing for Lyme disease has improved substantially; however, recovery by culture of the bacterium from skin biopsies of suspected patients is still the only definitive laboratory test. Reinfection of patients has been assumed to occur but as yet has not been documented by serial isolates from the same person. We present a case of culture-confirmed reinfection of a patient in Menominee County, Michigan. Borrelia burgdorferi was isolated from the skin punch biopsy specimens during each episode of erythema migrans (EM) and was subjected to molecular strain typing, genetic analysis of two outer surface protein genes, protein profile analysis, and serum antibody response testing. Results show that these isolates are distinct strains of the bacterium and that the two episodes of EM were caused by independent infections. This report describes the documented, culture-confirmed reinfection of a human by two different strains of B. burgdorferi.

scholarly journals Global Evolutionary Analysis of 11 Gene Families Part of Reactive Oxygen Species (ROS) Gene Network in Four Eucalyptus Species

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 257
Author(s):  
Qiang Li ◽  
Hélène San Clemente ◽  
Yongrui He ◽  
Yongyao Fu ◽  
Christophe Dunand
Keyword(s):  
Reactive Oxygen Species ◽  
Comparative Analysis ◽  
Gene Network ◽  
Expression Patterns ◽  
Reactive Oxygen ◽  
Evolutionary Process ◽  
Gene Families ◽  
Eucalyptus Species ◽  
Gene Gain ◽  
Oxygen Species

Eucalyptus is a worldwide hard-wood species which increasingly focused on. To adapt to various biotic and abiotic stresses, Eucalyptus have evolved complex mechanisms, increasing the cellular concentration of reactive oxygen species (ROS) by numerous ROS controlling enzymes. To better analyse the ROS gene network and discuss the differences between four Eucalyptus species, ROS gene network including 11 proteins families (1CysPrx, 2CysPrx, APx, APx-R, CIII Prx, Diox, GPx, Kat, PrxII, PrxQ and Rboh) were annotated and compared in an expert and exhaustive manner from the genomic data available from E. camaldulensis, E. globulus, E. grandis, and E. gunnii. In addition, a specific sequencing strategy was performed in order to determine if the missed sequences in at least one organism are the results of gain/loss events or only sequencing gaps. We observed that the automatic annotation applied to multigenic families is the source of miss-annotation. Base on the family size, the 11 families can be categorized into duplicated gene families (CIII Prx, Kat, 1CysPrx, and GPx), which contain a lot of gene duplication events and non-duplicated families (APx, APx-R, Rboh, DiOx, 2CysPrx, PrxII, and PrxQ). The gene family sizes are much larger in Eucalyptus than most of other angiosperms due to recent gene duplications, which could give higher adaptability to environmental changes and stresses. The cross-species comparative analysis shows gene gain and loss events during the evolutionary process. The 11 families possess different expression patterns, while in the Eucalyptus genus, the ROS families present similar expression patterns. Overall, the comparative analysis might be a good criterion to evaluate the adaptation of different species with different characters, but only if data mining is as exhaustive as possible. It is also a good indicator to explore the evolutionary process.

scholarly journals Vaccinia Virus Telomeres: Interaction with the Viral I1, I6, and K4 Proteins

2001 ◽  
Vol 75 (21) ◽  
pp. 10090-10105 ◽  
Author(s):  
Joseph DeMasi ◽  
Shan Du ◽  
David Lennon ◽  
Paula Traktman
Keyword(s):  
Complex Formation ◽  
Vaccinia Virus ◽  
Affinity Purification ◽  
Virus Genome ◽  
Specific Protein ◽  
Telomeric Sequence ◽  
Genome Replication ◽  
Mobility Shift ◽  
Infected Cells ◽  
Necessary And Sufficient

ABSTRACT The 192-kb linear DNA genome of vaccinia virus has covalently closed hairpin termini that are extremely AT rich and contain 12 extrahelical bases. Vaccinia virus telomeres have previously been implicated in the initiation of viral genome replication; therefore, we sought to determine whether the telomeres form specific protein-DNA complexes. Using an electrophoretic mobility shift assay, we found that extracts prepared from virions and from the cytoplasm of infected cells contain telomere binding activity. Four shifted complexes were detected using hairpin probes representing the viral termini, two of which represent an interaction with the “flip” isoform and two with the “flop” isoform. All of the specificity for protein binding lies within the terminal 65-bp hairpin sequence. Viral hairpins lacking extrahelical bases cannot form the shifted complexes, suggesting that DNA structure is crucial for complex formation. Using an affinity purification protocol, we purified the proteins responsible for hairpin-protein complex formation. The vaccinia virus I1 protein was identified as being necessary and sufficient for the formation of the upper doublet of shifted complexes, and the vaccinia virus I6 protein was shown to form the lower doublet of shifted complexes. Competition and challenge experiments confirmed that the previously uncharacterized I6 protein binds tightly and with great specificity to the hairpin form of the viral telomeric sequence. Incubation of viral hairpins with extracts from infected cells also generates a smaller DNA fragment that is likely to reflect specific nicking at the apex of the hairpin; we show that the vaccinia virus K4 protein is necessary and sufficient for this reaction. We hypothesize that these telomere binding proteins may play a role in the initiation of vaccinia virus genome replication and/or genome encapsidation.

scholarly journals Structure and Expression of the FlaA Periplasmic Flagellar Protein of Borrelia burgdorferi

1998 ◽  
Vol 180 (9) ◽  
pp. 2418-2425 ◽  
Author(s):  
Yigong Ge ◽  
Chunhao Li ◽  
Linda Corum ◽  
Clive A. Slaughter ◽  
Nyles W. Charon
Keyword(s):  
Borrelia Burgdorferi ◽  
Treponema Pallidum ◽  
The Other ◽  
Wild Type ◽  
Serpulina Hyodysenteriae ◽  
Flagellar Proteins ◽  
Flagellar Protein ◽  
Periplasmic Flagella ◽  
Triton X ◽  
Translational Level

ABSTRACT The spirochete which causes Lyme disease, Borrelia burgdorferi, has many features common to other spirochete species. Outermost is a membrane sheath, and within this sheath are the cell cylinder and periplasmic flagella (PFs). The PFs are subterminally attached to the cell cylinder and overlap in the center of the cell. Most descriptions of the B. burgdorferi flagellar filaments indicate that these organelles consist of only one flagellin protein (FlaB). In contrast, the PFs from other spirochete species are comprised of an outer layer of FlaA and a core of FlaB. We recently found that a flaA homolog was expressed in B. burgdorferi and that it mapped in a fla/che operon. These results led us to analyze the PFs and FlaA of B. burgdorferi in detail. Using Triton X-100 to remove the outer membrane and isolate the PFs, we found that the 38.0-kDa FlaA protein purified with the PFs in association with the 41.0-kDa FlaB protein. On the other hand, purifying the PFs by using Sarkosyl resulted in no FlaA in the isolated PFs. Sarkosyl has been used by others to purifyB. burgdorferi PFs, and our results explain in part their failure to find FlaA. Unlike other spirochetes, B. burgdorferi FlaA was expressed at a lower level than FlaB. In characterizing FlaA, we found that it was posttranslationally modified by glycosylation, and thus it resembles its counterpart fromSerpulina hyodysenteriae. We also tested if FlaA was synthesized in a spontaneously occurring PF mutant of B. burgdorferi (HB19Fla−). Although this mutant still synthesizedflaA message in amounts similar to the wild-type amounts, it failed to synthesize FlaA protein. These results suggest that, in agreement with data found for FlaB and other spirochete flagellar proteins, FlaA is likely to be regulated on the translational level. Western blot analysis using Treponema pallidum anti-FlaA serum indicated that FlaA was antigenically well conserved in several spirochete species. Taken together, the results indicate that both FlaA and FlaB comprise the PFs of B. burgdorferi and that they are regulated differently from flagellin proteins of other bacteria.

scholarly journals Conservation of the HBV RNA element epsilon in nackednaviruses reveals ancient origin of protein-primed reverse transcription

2021 ◽  
Vol 118 (13) ◽  
pp. e2022373118
Author(s):  
Jürgen Beck ◽  
Stefan Seitz ◽  
Chris Lauber ◽  
Michael Nassal
Keyword(s):  
Reverse Transcription ◽  
Specific Protein ◽  
Amino Acid Side Chain ◽  
Genome Replication ◽  
Phylogenetic Distance ◽  
Nucleotide Substitutions ◽  
Protein Priming ◽  
P Proteins ◽  
Cell Host Microbe

Hepadnaviruses, with the human hepatitis B virus as prototype, are small, enveloped hepatotropic DNA viruses which replicate by reverse transcription of an RNA intermediate. Replication is initiated by a unique protein-priming mechanism whereby a hydroxy amino acid side chain of the terminal protein (TP) domain of the viral polymerase (P) is extended into a short DNA oligonucleotide, which subsequently serves as primer for first-strand synthesis. A key component in the priming of reverse transcription is the viral RNA element epsilon, which contains the replication origin and serves as a template for DNA primer synthesis. Here, we show that recently discovered non-enveloped fish viruses, termed nackednaviruses [C. Lauber et al., Cell Host Microbe 22, 387–399 (2017)], employ a fundamentally similar replication mechanism despite their huge phylogenetic distance and major differences in genome organization and viral lifestyle. In vitro cross-priming studies revealed that few strategic nucleotide substitutions in epsilon enable site-specific protein priming by heterologous P proteins, demonstrating that epsilon is functionally conserved since the two virus families diverged more than 400 Mya. In addition, other cis elements crucial for the hepadnavirus-typical replication of pregenomic RNA into relaxed circular double-stranded DNA were identified at conserved positions in the nackednavirus genomes. Hence, the replication mode of both hepadnaviruses and nackednaviruses was already established in their Paleozoic common ancestor, making it a truly ancient and evolutionary robust principle of genome replication that is more widespread than previously thought.

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