Endogenous and Borrowed Proteolytic Activity in the Borrelia

2021 ◽  
Vol 85 (2) ◽  
Author(s):  
James L. Coleman ◽  
Jorge L. Benach ◽  
A. Wali Karzai
Keyword(s):  
Life Cycle ◽  
Lyme Disease ◽  
Adaptor Proteins ◽  
Physiological Changes ◽  
Relapsing Fever ◽  
Content Type ◽  
Outer Membranes ◽  
Tick Vector ◽  
Full Complement ◽  
Host Tissues

SUMMARY The Borrelia spp. are tick-borne pathogenic spirochetes that include the agents of Lyme disease and relapsing fever. As part of their life cycle, the spirochetes traffic between the tick vector and the vertebrate host, which requires significant physiological changes and remodeling of their outer membranes and proteome. This crucial proteome resculpting is carried out by a diverse set of proteases, adaptor proteins, and related chaperones. Despite its small genome, Borrelia burgdorferi has dedicated a large percentage of its genome to proteolysis, including a full complement of ATP-dependent proteases. Energy-driven proteolysis appears to be an important physiological feature of this dual-life-cycle bacterium. The proteolytic arsenal of Borrelia is strategically deployed for disposal of proteins no longer required as they move from one stage to another or are transferred from one host to another. Likewise, the Borrelia spp. are systemic organisms that need to break down and move through host tissues and barriers, and so their unique proteolytic resources, both endogenous and borrowed, make movement more feasible. Both the Lyme disease and relapsing fever Borrelia spp. bind plasminogen as well as numerous components of the mammalian plasminogen-activating system. This recruitment capacity endows the spirochetes with a borrowed proteolytic competency that can lead to increased invasiveness.

scholarly journals Blood Smears Have Poor Sensitivity for ConfirmingBorrelia miyamotoiDisease

2019 ◽  
Vol 57 (3) ◽  
Author(s):  
Sam R. Telford ◽  
Heidi K. Goethert ◽  
Philip J. Molloy ◽  
Victor Berardi
Keyword(s):  
Lyme Disease ◽  
Morphological Evidence ◽  
Hard Tick ◽  
Borrelia Miyamotoi ◽  
Relapsing Fever ◽  
Main Mode ◽  
Blood Samples ◽  
Content Type ◽  
Blood Smears ◽  
Thick Smear

ABSTRACTBorrelia miyamotoidisease (BMD) is a newly recognized borreliosis that is cotransmitted by ticks wherever Lyme disease is zoonotic. UnlikeBorrelia burgdorferisensu lato, the agent of Lyme disease,B. miyamotoiis closely related to relapsing fever spirochetes, such asBorrelia hermsii. Some authors have suggested that the disease caused byB. miyamotoishould be considered a hard-tick-transmitted relapsing fever, and thus, the main mode of confirming a diagnosis for that infection, microscopy to analyze a blood smear, may have clinical utility. To determine whether blood smears may detectB. miyamotoiin the blood of acute BMD patients, we made standard malariological thick smears from anticoagulated blood samples that were previously determined to contain this agent (by PCR) and analyzed them for morphological evidence of spirochetes. Spirochetes were not detected in the blood smears from 20 PCR positive patient blood samples after examination of 100 thick smear fields and only 2 of 20 demonstrated spirochetes when the examination was extended to 300 thick smear fields. Inoculation of severe combined immunodeficient (SCID) mice yielded isolates from 5 of 5 samples, but 0 of 3 BALB/c mice became infected. We conclude that in strong contrast to the diagnosis of typical relapsing fever, microscopy of blood smears is not sensitive enough for confirming a diagnosis of BMD but that SCID mouse inoculation could be a useful complement to PCR.

scholarly journals Imaging of Borrelia turicatae Producing the Green Fluorescent Protein Reveals Persistent Colonization of the Ornithodoros turicata Midgut and Salivary Glands from Nymphal Acquisition through Transmission

2016 ◽  
Vol 83 (5) ◽  
Author(s):  
Aparna Krishnavajhala ◽  
Hannah K. Wilder ◽  
William K. Boyle ◽  
Ashish Damania ◽  
Justin A. Thornton ◽  
...  
Keyword(s):  
Life Cycle ◽  
Green Fluorescent Protein ◽  
Salivary Glands ◽  
Fluorescent Protein ◽  
Blood Feeding ◽  
Relapsing Fever ◽  
Tick Feeding ◽  
Content Type ◽  
Green Fluorescent ◽  
Infectious Cycle

ABSTRACT Relapsing fever (RF) spirochetes colonize and are transmitted to mammals primarily by Ornithodoros ticks, and little is known regarding the pathogen's life cycle in the vector. To further understand vector colonization and transmission of RF spirochetes, Borrelia turicatae expressing a green fluorescent protein (GFP) marker (B. turicatae-gfp) was generated. The transformants were evaluated during the tick-mammal infectious cycle, from the third nymphal instar to adult stage. B. turicatae-gfp remained viable for at least 18 months in starved fourth-stage nymphal ticks, and the studies indicated that spirochete populations persistently colonized the tick midgut and salivary glands. Our generation of B. turicatae-gfp also revealed that within the salivary glands, spirochetes are localized in the ducts and lumen of acini, and after tick feeding, the tissues remained populated with spirochetes. The B. turicatae-gfp generated in this study is an important tool to further understand and define the mechanisms of vector colonization and transmission. IMPORTANCE In order to interrupt the infectious cycle of tick-borne relapsing fever spirochetes, it is important to enhance our understanding of vector colonization and transmission. Toward this, we generated a strain of Borrelia turicatae that constitutively produced the green fluorescent protein, and we evaluated fluorescing spirochetes during the entire infectious cycle. We determined that the midgut and salivary glands of Ornithodoros turicata ticks maintain the pathogens throughout the vector's life cycle and remain colonized with the spirochetes for at least 18 months. We also determined that the tick's salivary glands were not depleted after a transmission blood feeding. These findings set the framework to further understand the mechanisms of midgut and salivary gland colonization.

scholarly journals Cotransmission of Divergent Relapsing Fever Spirochetes by Artificially Infected Ornithodoros hermsi

2011 ◽  
Vol 77 (24) ◽  
pp. 8494-8499 ◽  
Author(s):  
Paul F. Policastro ◽  
Sandra J. Raffel ◽  
Tom G. Schwan
Keyword(s):  
Soft Tick ◽  
Relapsing Fever ◽  
Rodent Host ◽  
Borrelia Hermsii ◽  
Content Type ◽  
Tick Vector ◽  
Tick Infection ◽  
Group I ◽  
Ornithodoros Hermsi ◽  
Feeding Tick

ABSTRACTThe soft tickOrnithodoros hermsi, which ranges in specific arboreal zones of western North America, acts as a vector for the relapsing fever spirocheteBorrelia hermsii. Two genomic groups (genomic group I [GGI] and GGII) ofB. hermsiiare differentiated by multilocus sequence typing yet are codistributed in much of the vector's range. To test whether the tick vector can be infected via immersion, noninfected, colony-derivedO. hermsilarvae were exposed to reduced-humidity conditions before immersion in culture suspensions of several GGI and GGII isolates. We tested for spirochetes in ticks by immunofluorescence microscopy and in mouse blood by quantitative PCR of thevtplocus to differentiate spirochete genotypes. The immersed larval ticks were capable of spirochete transmission to mice at the first nymphal feeding. Tick infection with mixed cultures of isolates DAH (vtp-6) (GGI) and MTW-2 (vtp-5) (GGII) resulted in ticks that caused spirochetemias in mice consisting of MTW-2 or both DAH and MTW-2. These findings show that this soft tick species can acquireB. hermsiiby immersion in spirochete suspensions, that GGI and GGII isolates can coinfect the tick vector by this method, and that these spirochetes can be cotransmitted to a rodent host.

scholarly journals Dispensable Role of Mitochondrial Fission Protein 1 (Fis1) in the Erythrocytic Development of Plasmodium falciparum

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Mulaka Maruthi ◽  
Liqin Ling ◽  
Jing Zhou ◽  
Hangjun Ke
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Outer Membrane ◽  
Malaria Parasite ◽  
Mitochondrial Fission ◽  
Adaptor Proteins ◽  
Mitochondrial Outer Membrane ◽  
Content Type ◽  
Single Mitochondrion

ABSTRACT Malaria remains a huge global health burden, and control of this disease has run into a severe bottleneck. To defeat malaria and reach the goal of eradication, a deep understanding of the parasite biology is urgently needed. The mitochondrion of the malaria parasite is essential throughout the parasite’s life cycle and has been validated as a clinical drug target. In the asexual development of Plasmodium spp., the single mitochondrion grows from a small tubular structure to a complex branched network. This branched mitochondrion is divided at the end of schizogony when 8 to 32 daughter cells are produced, distributing one mitochondrion to each forming merozoite. In mosquito and liver stages, the giant mitochondrial network is split into thousands of pieces and daughter mitochondria are segregated into individual progeny. Despite the significance of mitochondrial fission in Plasmodium, the underlying mechanism is largely unknown. Studies of mitochondrial fission in model eukaryotes have revealed that several mitochondrial fission adaptor proteins are involved in recruiting dynamin GTPases to physically split mitochondrial membranes. Apicomplexan parasites, however, share no identifiable homologs of mitochondrial fission adaptor proteins with yeast or humans, except for Fis1. Here, we investigated the localization and essentiality of the Fis1 homolog in Plasmodium falciparum, PfFis1 (PF3D7_1325600), during the asexual life cycle. We found that PfFis1 requires an intact C terminus for mitochondrial localization but is not essential for parasite development or mitochondrial fission. The dispensable role of PfFis1 indicates that Plasmodium contains additional fission adaptor proteins on the mitochondrial outer membrane that could be essential for mitochondrial fission. IMPORTANCE Malaria is responsible for over 230 million clinical cases and ∼half a million deaths each year. The single mitochondrion of the malaria parasite functions as a metabolic hub throughout the parasite’s developmental cycle (DC) and also as a source of ATP in certain stages. To pass on its essential functions, the parasite’s mitochondrion needs to be properly divided and segregated into all progeny during cell division via a process termed mitochondrial fission. Due to the divergent nature of Plasmodium spp., the molecular players involved in mitochondrial fission and their mechanisms of action remain largely unknown. Here, we found that the only identifiable mitochondrial fission adaptor protein that is evolutionarily conserved in the Apicomplexan phylum, Fis1, it not essential in P. falciparum asexual stages. Our data suggest that malaria parasites use redundant fission adaptor proteins on the mitochondrial outer membrane to mediate the fission process.

scholarly journals Structure, Function, and Interactions of the HIV-1 Capsid Protein

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 100
Author(s):  
Eric Rossi ◽  
Megan E. Meuser ◽  
Camille J. Cunanan ◽  
Simon Cocklin
Keyword(s):  
Life Cycle ◽  
Capsid Protein ◽  
Adaptor Proteins ◽  
Restriction Factors ◽  
Gag Polyprotein ◽  
Immunodeficiency Virus ◽  
Host Cell Factors ◽  
Hiv 1

The capsid (CA) protein of the human immunodeficiency virus type 1 (HIV-1) is an essential structural component of a virion and facilitates many crucial life cycle steps through interactions with host cell factors. Capsid shields the reverse transcription complex from restriction factors while it enables trafficking to the nucleus by hijacking various adaptor proteins, such as FEZ1 and BICD2. In addition, the capsid facilitates the import and localization of the viral complex in the nucleus through interaction with NUP153, NUP358, TNPO3, and CPSF-6. In the later stages of the HIV-1 life cycle, CA plays an essential role in the maturation step as a constituent of the Gag polyprotein. In the final phase of maturation, Gag is cleaved, and CA is released, allowing for the assembly of CA into a fullerene cone, known as the capsid core. The fullerene cone consists of ~250 CA hexamers and 12 CA pentamers and encloses the viral genome and other essential viral proteins for the next round of infection. As research continues to elucidate the role of CA in the HIV-1 life cycle and the importance of the capsid protein becomes more apparent, CA displays potential as a therapeutic target for the development of HIV-1 inhibitors.

scholarly journals Multispecies Transcriptomics Data Set of Brugia malayi, Its Wolbachia Endosymbiont wBm, and Aedes aegypti across the B. malayi Life Cycle

2018 ◽  
Vol 7 (18) ◽  
Author(s):  
Matthew Chung ◽  
Laura Teigen ◽  
Silvia Libro ◽  
Robin E. Bromley ◽  
Nikhil Kumar ◽  
...  
Keyword(s):  
Life Cycle ◽  
Aedes Aegypti ◽  
Brugia Malayi ◽  
Adult Males ◽  
Data Set ◽  
Content Type ◽  
Transcriptomics Data ◽  
Wolbachia Endosymbiont ◽  
Males And Females ◽  
Stage 1

Here, we present a comprehensive transcriptomics data set of Brugia malayi, its Wolbachia endosymbiont wBm, and its vector host. This study samples from 16 stages across the entire B. malayi life cycle, including stage 1 through 4 larvae, adult males and females, embryos, immature microfilariae, and mature microfilariae.

scholarly journals The Western Progression of Lyme Disease: Infectious and NonclonalBorrelia burgdorferi Sensu LatoPopulations in Grand Forks County, North Dakota

2014 ◽  
Vol 81 (1) ◽  
pp. 48-58 ◽  
Author(s):  
Brandee L. Stone ◽  
Nathan M. Russart ◽  
Robert A. Gaultney ◽  
Angela M. Floden ◽  
Jefferson A. Vaughan ◽  
...  
Keyword(s):  
Lyme Disease ◽  
16S Rrna ◽  
16S Rrna Gene ◽  
North Dakota ◽  
Intergenic Spacer ◽  
Rrna Gene ◽  
Content Type ◽  
Intergenic Spacer Region ◽  
Grand Forks ◽  
The 16S Rrna Gene

ABSTRACTScant attention has been paid to Lyme disease,Borrelia burgdorferi,Ixodes scapularis, or reservoirs in eastern North Dakota despite the fact that it borders high-risk counties in Minnesota. Recent reports ofB. burgdorferiandI. scapularisin North Dakota, however, prompted a more detailed examination. Spirochetes cultured from the hearts of five rodents trapped in Grand Forks County, ND, were identified asB. burgdorferi sensu latothrough sequence analyses of the 16S rRNA gene, the 16S rRNA gene-ileTintergenic spacer region,flaB,ospA,ospC, andp66. OspC typing revealed the presence of groups A, B, E, F, L, and I. Two rodents were concurrently carrying multiple OspC types. Multilocus sequence typing suggested the eastern North Dakota strains are most closely related to those found in neighboring regions of the upper Midwest and Canada. BALB/c mice were infected withB. burgdorferiisolate M3 (OspC group B) by needle inoculation or tick bite. Tibiotarsal joints and ear pinnae were culture positive, andB. burgdorferiM3 was detected by quantitative PCR (qPCR) in the tibiotarsal joints, hearts, and ear pinnae of infected mice. Uninfected larvalI. scapularisticks were able to acquireB. burgdorferiM3 from infected mice; M3 was maintained inI. scapularisduring the molt from larva to nymph; and further, M3 was transmitted from infectedI. scapularisnymphs to naive mice, as evidenced by cultures and qPCR analyses. These results demonstrate that isolate M3 is capable of disseminated infection by both artificial and natural routes of infection. This study confirms the presence of unique (nonclonal) and infectiousB. burgdorferipopulations in eastern North Dakota.

scholarly journals Characterization and Molecular Epidemiology of a Fungal Infection of Edible Crabs (Cancer pagurus) and Interaction of the Fungus with the Dinoflagellate Parasite Hematodinium

2012 ◽  
Vol 79 (3) ◽  
pp. 783-793 ◽  
Author(s):  
Amanda L. Smith ◽  
Kristina M. Hamilton ◽  
Lucy Hirschle ◽  
Emma C. Wootton ◽  
Claire L. Vogan ◽  
...  
Keyword(s):  
Ribosomal Dna ◽  
Host Response ◽  
Small Subunit ◽  
Fungal Isolate ◽  
Content Type ◽  
Cancer Pagurus ◽  
South Wales ◽  
Disease Condition ◽  
Fungal Sepsis ◽  
Host Tissues

ABSTRACTThis study reports on an emerging fungal disease of the edible crab,Cancer pagurus. Juvenile (prerecruit) crabs were found to be subject to this disease condition during the months of May to September at two intertidal sites in South Wales, United Kingdom. Histopathology revealed that the fungi overwhelm the host response in the tissues, leading to progressive septicemia. The causative agent of this infection was isolated and grown in pure culture and was identified as a member of theOphiocordycepsclade by sequencing of the small subunit of the fungal ribosomal DNA (rDNA). Of the crabs naturally infected with the fungus, 94% had a coinfection with the parasitic dinoflagellateHematodiniumspecies. To determine if there was any interaction between the two disease-causing agents, apparently fungus-free crabs, both with and without naturalHematodiniuminfections, were challenged with the fungal isolate. The presence ofHematodiniumcaused a significant reduction in fungal multiplication in the hemocoel of the crabs in comparison to that inHematodinium-free individuals. Histopathology of coinfected crabs showed a systemic multiplication ofHematodiniumwithin host tissues, leading to a rapid death, whileHematodinium-free crabs experimentally infected with the fungal isolate died due to fungal sepsis (septicemia) with the same characteristic pathology as seen in natural infections.

The use of the risk assessment in the life cycle assessment framework

2015 ◽  
Vol 26 (3) ◽  
pp. 389-406 ◽  
Author(s):  
Maria Francesca Milazzo ◽  
Francesco Spina
Keyword(s):  
Risk Assessment ◽  
Life Cycle Assessment ◽  
Life Cycle ◽  
Human Health ◽  
Biodiesel Production ◽  
Health Impacts ◽  
Complete Analysis ◽  
Transfer Factors ◽  
Content Type ◽  
Human Health Impacts

Purpose – The purpose of this paper is to quantify the human health impacts of soy-biodiesel production with the aim to discuss about its environmental sustainability. Design/methodology/approach – The integrated use of two current approaches, risk assessment (RA) and life cycle assessment (LCA), has allowed improvement of the potentialities of both in obtaining a more complete analysis. The implementation of a life cycle indicator for the assessment of the impacts on the human health, integrating the features of both approaches, is the main focus of this paper. Findings – It has been found that, although the biodiesel is a green fuel, it has some criticalities in its life cycle, which cannot be disregarded. In fact, even if biodiesel is essentially a clean fuel there are some phases, prior to the industrial phase, that can cause negative effects on human health and ecosystems. Practical implications – Results suggest some measures which can be adopted to substantially reduce human health impacts. Further alternative could be analysed in future to gain more insight about the use of biodiesel fuels. Originality/value – The estimation of the impacts of a process producing biodiesel has been made by using a novel approach. The novelty is associated with the calculation of the impacts on human health by using the transfer factors applied in RA. The use of such factors, properly modified in order to estimate the impacts on a wider scale than a site-dimension, allows defining a holistic approach, as LCA and RA are used as complete units but at the same time can be related to each other.

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