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  1. Article ; Online: The "Biological Weapons" of

    Rikihisa, Yasuko

    Frontiers in cellular and infection microbiology

    2022  Volume 11, Page(s) 830180

    Abstract: Ehrlichia ... ...

    Abstract Ehrlichia chaffeensis
    MeSH term(s) Autophagy ; Biological Warfare Agents ; Ehrlichia chaffeensis/metabolism ; Ehrlichiosis/microbiology ; Humans ; Monocytes/metabolism
    Chemical Substances Biological Warfare Agents
    Language English
    Publishing date 2022-01-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2021.830180
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  2. Article: Analysis of

    Kumar, Deepak / Budachetri, Khemraj / Rikihisa, Yasuko / Karim, Shahid

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Background: MicroRNAs (miRNAs) represent a subset of small noncoding RNAs and carry tremendous potential for regulating gene expression at the post-transcriptional level. They play pivotal roles in distinct cellular mechanisms including inhibition of ... ...

    Abstract Background: MicroRNAs (miRNAs) represent a subset of small noncoding RNAs and carry tremendous potential for regulating gene expression at the post-transcriptional level. They play pivotal roles in distinct cellular mechanisms including inhibition of bacterial, parasitic, and viral infections via immune response pathways. Intriguingly, pathogens have developed strategies to manipulate the host's miRNA profile, fostering environments conducive to successful infection. Therefore, changes in an arthropod host's miRNA profile in response to pathogen invasion could be critical in understanding host-pathogen dynamics. Additionally, this area of study could provide insights into discovering new targets for disease control and prevention. The main objective of the present study is to investigate the functional role of differentially expressed miRNAs upon
    Methods: Small RNA libraries from uninfected and
    Results: The sequencing of small RNA libraries generated >147 million raw reads in all four libraries and identified a total of >250 miRNAs across the four libraries. We identified 23 and 14 differentially expressed miRNAs in salivary glands, and midgut tissues infected with
    Conclusions: The current study identified known and novel miRNAs and suggests that interfering with these miRNAs may impact the vectorial capacity of ticks to harbor
    Language English
    Publishing date 2024-05-06
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.05.03.592465
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Role and Function of the Type IV Secretion System in Anaplasma and Ehrlichia Species.

    Rikihisa, Yasuko

    Current topics in microbiology and immunology

    2018  Volume 413, Page(s) 297–321

    Abstract: The obligatory intracellular pathogens Anaplasma phagocytophilum and Ehrlichia chaffeensis proliferate within membrane-bound vacuoles of human leukocytes and cause potentially fatal emerging infectious diseases. Despite the reductive genome evolution in ... ...

    Abstract The obligatory intracellular pathogens Anaplasma phagocytophilum and Ehrlichia chaffeensis proliferate within membrane-bound vacuoles of human leukocytes and cause potentially fatal emerging infectious diseases. Despite the reductive genome evolution in this group of bacteria, genes encoding the type IV secretion system (T4SS), which is homologous to the VirB/VirD4 system of the plant pathogen Agrobacterium tumefaciens, have been expanded and are highly expressed in A. phagocytophilum and E. chaffeensis in human cells. Of six T4SS effector proteins identified in them, roles and functions have been described so far only for ankyrin repeat domain-containing protein A (AnkA), Anaplasma translocated substrate 1 (Ats-1), and Ehrlichia translocated factor 1 (Etf-1, ECH0825). These effectors are abundantly produced and secreted into the host cytoplasm during infection, but not toxic to host cells. They contain eukaryotic protein motifs or organelle localization signals and have distinct subcellular localization, target to specific host cell molecules to promote infection. Ats-1 and Etf-1 are orthologous proteins, subvert two important innate immune mechanisms against intracellular infection, cellular apoptosis and autophagy, and manipulate autophagy to gain nutrients from host cells. Although Ats-1 and Etf-1 have similar functions and roles in obligatory intracellular infection, they are specifically adapted to the distinct membrane-bound intracellular niche of A. phagocytophilum and E. chaffeensis, respectively. Ectopic expression of these effectors enhances respective bacterial infection, whereas intracellular delivery of antibodies against these effectors or targeted knockdown of the effector with antisense peptide nucleic acid significantly impairs bacterial infection. Thus, both T4SSs have evolved as important survival and nutritional virulence mechanism in these obligatory intracellular bacteria. Future studies on the functions of Anaplasma and Ehrlichia T4SS effector molecules and signaling pathways will undoubtedly advance our understanding of the complex interplay between obligatory intracellular pathogens and their hosts. Such data can be applied toward the treatment and control of anaplasmosis and ehrlichiosis.
    MeSH term(s) Anaplasma ; Animals ; Bacterial Proteins ; Ehrlichia chaffeensis ; Ehrlichiosis ; Humans ; Type IV Secretion Systems
    Chemical Substances Bacterial Proteins ; Type IV Secretion Systems
    Language English
    Publishing date 2018-05-19
    Publishing country Germany
    Document type Journal Article
    ISSN 0070-217X
    ISSN 0070-217X
    DOI 10.1007/978-3-319-75241-9_12
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  4. Article ; Online: Subversion of RAB5-regulated autophagy by the intracellular pathogen

    Rikihisa, Yasuko

    Small GTPases

    2017  Volume 10, Issue 5, Page(s) 343–349

    Abstract: Intracellular pathogens often exploit RAB functions to establish a safe haven in which to survive and proliferate. ...

    Abstract Intracellular pathogens often exploit RAB functions to establish a safe haven in which to survive and proliferate.
    MeSH term(s) Animals ; Autophagic Cell Death ; Class III Phosphatidylinositol 3-Kinases/metabolism ; Ehrlichia chaffeensis/physiology ; Ehrlichiosis/metabolism ; Ehrlichiosis/pathology ; Endosomes/metabolism ; Endosomes/microbiology ; Host-Parasite Interactions/physiology ; Humans ; Lysosomes/metabolism ; Lysosomes/microbiology ; Type IV Secretion Systems/metabolism ; rab5 GTP-Binding Proteins/metabolism
    Chemical Substances Type IV Secretion Systems ; Class III Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; RAB5C protein, human (EC 3.6.1.-) ; rab5 GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2017-07-05
    Publishing country United States
    Document type Journal Article ; Review ; Video-Audio Media
    ZDB-ID 2682247-7
    ISSN 2154-1256 ; 2154-1248
    ISSN (online) 2154-1256
    ISSN 2154-1248
    DOI 10.1080/21541248.2017.1332506
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  5. Article ; Online: Rab27a via its effector JFC1 localizes to Anaplasma inclusions and promotes Anaplasma proliferation in leukocytes.

    Huang, Weiyan / Lin, Mingqun / Rikihisa, Yasuko

    Microbes and infection

    2023  , Page(s) 105278

    Abstract: Anaplasma phagocytophilum is an obligatory intracellular bacterium that causes tick-borne zoonosis called human granulocytic anaplasmosis. Mechanisms by which Anaplasma replicates inside of the membrane-bound compartment called "inclusion" in neutrophils ...

    Abstract Anaplasma phagocytophilum is an obligatory intracellular bacterium that causes tick-borne zoonosis called human granulocytic anaplasmosis. Mechanisms by which Anaplasma replicates inside of the membrane-bound compartment called "inclusion" in neutrophils are incompletely understood. A small GTPase Rab27a is found in the secretory granules and multivesicular endosomes. In this study we found Rab27a-containing granules were localized to Anaplasma inclusions in guanine nucleotide-dependent manner, and constitutively active Rab27a enhanced Anaplasma infection and dominant-negative Rab27a inhibited Anaplasma infection. Rab27a effector, JFC1 is known to mediate docking/fusion of Rab27a-bearing granules for exocytosis in leukocytes. shRNA stable knockdown of Rab27a or JFC1 inhibited Anaplasma infection in HL-60 cells. Similar to Rab27a, both endogenous and transfected JFC1 were localized to Anaplasma inclusions by immunostaining or live cell imaging. The JFC1 C2A domain that binds 3'-phosphoinositides, was sufficient and required for JFC1 and Rab27a localization to Anaplasma inclusions which were enriched with phosphatidylinositol 3-phosphate. Nexinhib20, the small molecule inhibitor specific to Rab27a and JFC1 binding, inhibited Anaplasma infection. Taken together, these results imply elevated phosphatidylinositol 3-phosphate in the inclusion membrane recruits JFC1 to mediate Rab27a-bearing granules/vesicles to dock/fuse with Anaplasma inclusions, the lumen of which is topologically equivalent to the exterior of the cell to benefit Anaplasma proliferation.
    Language English
    Publishing date 2023-12-16
    Publishing country France
    Document type Journal Article
    ZDB-ID 1465093-9
    ISSN 1769-714X ; 1286-4579
    ISSN (online) 1769-714X
    ISSN 1286-4579
    DOI 10.1016/j.micinf.2023.105278
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  6. Article ; Online: Inhibition of

    Lin, Mingqun / Koley, Amritendu / Zhang, Wenqing / Pei, Dehua / Rikihisa, Yasuko

    PNAS nexus

    2023  Volume 2, Issue 2, Page(s) pgad017

    Abstract: Ehrlichia ... ...

    Abstract Ehrlichia chaffeensis
    Language English
    Publishing date 2023-01-27
    Publishing country England
    Document type Journal Article
    ISSN 2752-6542
    ISSN (online) 2752-6542
    DOI 10.1093/pnasnexus/pgad017
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  7. Article ; Online: Correction for Zhi et al., "Cloning and Expression of the 44-Kilodalton Major Outer Membrane Protein Gene of the Human Granulocytic Ehrlichiosis Agent and Application of the Recombinant Protein to Serodiagnosis".

    Zhi, N / Ohashi, N / Rikihisa, Y / Horowitz, H W / Wormser, G P / Hechemy, K

    Journal of clinical microbiology

    2023  Volume 61, Issue 10, Page(s) e0070323

    Language English
    Publishing date 2023-09-07
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 390499-4
    ISSN 1098-660X ; 0095-1137
    ISSN (online) 1098-660X
    ISSN 0095-1137
    DOI 10.1128/jcm.00703-23
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  8. Article ; Online: Molecular Pathogenesis of Ehrlichia chaffeensis Infection.

    Rikihisa, Yasuko

    Annual review of microbiology

    2015  Volume 69, Page(s) 283–304

    Abstract: Ehrlichia chaffeensis is an obligatory intracellular and cholesterol-dependent bacterium that has evolved special proteins and functions to proliferate inside leukocytes and cause disease. E. chaffeensis has a multigene family of major outer membrane ... ...

    Abstract Ehrlichia chaffeensis is an obligatory intracellular and cholesterol-dependent bacterium that has evolved special proteins and functions to proliferate inside leukocytes and cause disease. E. chaffeensis has a multigene family of major outer membrane proteins with porin activity and induces infectious entry using its entry-triggering protein to bind the human cell surface protein DNase X. During intracellular replication, three functional pairs of two-component systems are sequentially expressed to regulate metabolism, aggregation, and the development of stress-resistance traits for transmission. A type IV secretion effector of E. chaffeensis blocks mitochondrion-mediated host cell apoptosis. Several type I secretion proteins are secreted at the Ehrlichia-host interface. E. chaffeensis strains induce strikingly variable inflammation in mice. The central role of MyD88, but not Toll-like receptors, suggests that Ehrlichia species have unique inflammatory molecules. A recent report about transient targeted mutagenesis and random transposon mutagenesis suggests that stable targeted knockouts may become feasible in Ehrlichia.
    MeSH term(s) Animals ; Ehrlichia chaffeensis/physiology ; Ehrlichiosis/immunology ; Ehrlichiosis/microbiology ; Ehrlichiosis/pathology ; Humans ; Inflammation ; Leukocytes/microbiology ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Type IV Secretion Systems
    Chemical Substances Reactive Oxygen Species ; Type IV Secretion Systems
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 207931-8
    ISSN 1545-3251 ; 0066-4227
    ISSN (online) 1545-3251
    ISSN 0066-4227
    DOI 10.1146/annurev-micro-091014-104411
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  9. Article ; Online: Ehrlichia chaffeensis Uses an Invasin To Suppress Reactive Oxygen Species Generation by Macrophages via CD147-Dependent Inhibition of Vav1 To Block Rac1 Activation.

    Teymournejad, Omid / Rikihisa, Yasuko

    mBio

    2020  Volume 11, Issue 2

    Abstract: The obligatory intracellular ... ...

    Abstract The obligatory intracellular pathogen
    MeSH term(s) Adhesins, Bacterial/genetics ; Adhesins, Bacterial/metabolism ; Animals ; Basigin/genetics ; Basigin/metabolism ; Ehrlichia chaffeensis/physiology ; Humans ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/microbiology ; Mice ; Mice, Knockout ; Monocytes/immunology ; Monocytes/metabolism ; Monocytes/microbiology ; Proto-Oncogene Proteins c-vav/antagonists & inhibitors ; Reactive Oxygen Species/metabolism ; rac1 GTP-Binding Protein/antagonists & inhibitors ; rac1 GTP-Binding Protein/metabolism
    Chemical Substances Adhesins, Bacterial ; Proto-Oncogene Proteins c-vav ; Reactive Oxygen Species ; Vav1 protein, mouse ; Basigin (136894-56-9) ; rac1 GTP-Binding Protein (EC 3.6.5.2)
    Language English
    Publishing date 2020-04-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.00267-20
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  10. Article ; Online: Carbon monoxide combined with artificial blood cells acts as an antioxidant for tissues thermally-damaged by dye laser irradiation.

    Rikihisa, Naoaki / Shimanouchi, Kae / Saito, Yoshiaki / Sakai, Hiromi / Mitsukawa, Nobuyuki

    Burns : journal of the International Society for Burn Injuries

    2022  Volume 49, Issue 2, Page(s) 388–400

    Abstract: Artificial red blood cells [i.e., hemoglobin vesicles (HbVs)] can be used as photosensitizers in pulsed-dye laser (PDL) treatment for port wine stains in animal models. Small HbVs are distributed in the vicinity of the endothelial cells of the blood ... ...

    Abstract Artificial red blood cells [i.e., hemoglobin vesicles (HbVs)] can be used as photosensitizers in pulsed-dye laser (PDL) treatment for port wine stains in animal models. Small HbVs are distributed in the vicinity of the endothelial cells of the blood vessels. In our previous in vivo experiments, both HbVs and red blood cells absorbed photons of the laser and generated heat, contributing to removal of very small blood vessels and large deeper subcutaneous blood vessels with PDL irradiation. Herein, we tested carbon monoxide-bound HbVs (CO-HbVs) that would produce heat energy while releasing CO in vessels after dye laser irradiation in a rabbit auricle model. We conducted this experiment to confirm secondary progression of thermal injury being reduced with the antioxidative property of CO. We histopathologically evaluated the damages to the large vessels and surrounding dermal tissue following PDL irradiation alone or subsequent to the intravenous injection of the qualified HbVs. The soft tissue damages were graded on a five-point scale and compared statistically. Intravenous CO-HbVs significantly reduced damage to the surrounding tissue after subsequent PDL irradiation; however, the degree of damage to the larger vessel wall resulted in a variety of changes, including a slight increase in our histopathological grades. This beneficial effect in dye laser treatment for port wine stains may be the result of the antioxidative property of CO against free radicals in the zone of stasis that may still be theoretically viable in burns. This effect of CO protecting tissues from thermal damage is consistent with previous reports of CO as a reducing agent. If the reducing agent can be delivered directly to the affected area immediately after the burn injury, even in a small amount, the complex inflammatory cascade may be reduced and unnecessary inflammation after laser treatment that lowers the patient's quality of life can be avoided.
    MeSH term(s) Animals ; Rabbits ; Port-Wine Stain/pathology ; Blood Substitutes ; Antioxidants ; Carbon Monoxide ; Lasers, Dye ; Endothelial Cells ; Reducing Agents ; Quality of Life ; Burns ; Hemoglobins
    Chemical Substances Blood Substitutes ; Antioxidants ; Carbon Monoxide (7U1EE4V452) ; Reducing Agents ; Hemoglobins
    Language English
    Publishing date 2022-03-19
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 197308-3
    ISSN 1879-1409 ; 0305-4179
    ISSN (online) 1879-1409
    ISSN 0305-4179
    DOI 10.1016/j.burns.2022.03.009
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