The composition of cytoplasmic vacuoles containing the agent of Human Granulocytic Ehrlichiosis (HGE) was studied to investigate how this pathogen exists within infected host cells. Electron microscopy demonstrated that the HGE organism resides in a membrane-bound compartment within HL-60 cells: early forms of the HGE agent have a round reticular appearance while later structures are small and dense. Vacuoles containing HGE bacteria incorporated endocytosed colloidal gold particles, suggesting that they are part of the endocytic pathway. Antibodies directed to the mannose-6-phosphate receptor labeled vacuole membranes. Antibodies to the transferrin receptor and to the lysosomal membrane glycoprotein LAMP 1 did not. Moreover, 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine, which normally accumulates in compartments with low pH, was not present inside these vacuoles. These results suggest that vacuoles containing the agent of HGE fail to mature into phagolysosomes. We conclude that the agent of HGE appears to enter and modify part of the endocytic pathway.
P Webster, J W IJdo, L M Chicoine, E Fikrig
Title and authors | Publication | Year |
---|---|---|
Establishing the intracellular niche of obligate intracellular vacuolar pathogens.
Clemente TM, Angara RK, Gilk SD |
Frontiers in Cellular and Infection Microbiology | 2023 |
The Obligate Intracellular Bacterial Pathogen Anaplasma phagocytophilum Exploits Host Cell Multivesicular Body Biogenesis for Proliferation and Dissemination.
Read CB, Lind MCH, Chiarelli TJ, Izac JR, Adcox HE, Marconi RT, Carlyon JA |
mBio | 2022 |
Functional inhibition of acid sphingomyelinase disrupts infection by intracellular bacterial pathogens
CL Cockburn, RS Green, SR Damle, RK Martin, NN Ghahrai, PM Colonne, MS Fullerton, DH Conrad, CE Chalfant, DE Voth, EA Rucks, SD Gilk, JA Carlyon |
2019 | |
Anaplasmataceae Subversion of the Lysosomal Activity
RN Alves |
2018 | |
Manipulation of Host Cholesterol by Obligate Intracellular Bacteria
D Samanta, M Mulye, TM Clemente, AV Justis, SD Gilk |
Frontiers in Cellular and Infection Microbiology | 2017 |
Anaplasma phagocytophilum infection modulates expression of megakaryocyte cell cycle genes through phosphatidylinositol-3-kinase signaling
S Khanal, H Sultana, JD Catravas, JA Carlyon, G Neelakanta, UG Munderloh |
PloS one | 2017 |
Type IV Secretion in Gram-Negative and Gram-Positive Bacteria
S Backert, E Grohmann |
2017 | |
Anaplasma marginale Actively Modulates Vacuolar Maturation during Intracellular Infection of Its Tick Vector, Dermacentor andersoni
F Magunda, CW Thompson, DA Schneider, SM Noh, HL Drake |
Applied and environmental microbiology | 2016 |
Deviant Behavior: Tick-Borne Pathogens and Inflammasome Signaling
D Shaw, E McClure, X Wang, J Pedra |
Veterinary Sciences | 2016 |
Rapid Sequestration of Leishmania mexicana by Neutrophils Contributes to the Development of Chronic Lesion
BP Hurrell, S Schuster, E Grün, M Coutaz, RA Williams, W Held, B Malissen, M Malissen, S Yousefi, HU Simon, AJ Müller, F Tacchini-Cottier, I Müller |
PLoS pathogens | 2015 |
Bergey's Manual of Systematics of Archaea and Bacteria
CC Kuo, RS Stephens, PM Bavoil, B Kaltenboeck |
Bergey's Manual of Systematics of Archaea and Bacteria | 2015 |
Subversion of NPC1 pathway of cholesterol transport by Anaplasma phagocytophilum
Q Xiong, Y Rikihisa |
Cellular Microbiology | 2012 |
Intracellular Pathogens II: Rickettsiales
GH Palmer, AF Azad |
2012 | |
Mechanisms of Obligatory Intracellular Infection with Anaplasma phagocytophilum
Y Rikihisa |
Clinical microbiology reviews | 2011 |
Monoubiquitinated proteins decorate the Anaplasma phagocytophilum-occupied vacuolar membrane
B Huang, N Ojogun, SA Ragland, JA Carlyon |
FEMS Immunology & Medical Microbiology | 2011 |
Tropical Infectious Diseases: Principles, Pathogens and Practice
TB Nutman, JW Kazura |
Tropical Infectious Diseases: Principles, Pathogens and Practice | 2011 |
Proteomic Analysis of Anaplasma phagocytophilum during Infection of Human Myeloid Cells Identifies a Protein That Is Pronouncedly Upregulated on the Infectious Dense-Cored Cell
MJ Troese, A Kahlon, SA Ragland, AK Ottens, N Ojogun, KT Nelson, NJ Walker, DL Borjesson, JA Carlyon, RP Morrison |
Infection and immunity | 2011 |
Topley & Wilson's Microbiology and Microbial Infections
PM Pitha, MS Künzi |
Topley & Wilson's Microbiology and Microbial Infections | 2010 |
Human ehrlichiosis and anaplasmosis
N Ismail, KC Bloch, JW McBride |
Clinics in Laboratory Medicine | 2010 |
Molecular events involved in cellular invasion by Ehrlichia chaffeensis and Anaplasma phagocytophilum
Y Rikihisa |
Veterinary Parasitology | 2010 |
Anaplasma phagocytophilum and Ehrlichia chaffeensis: subversive manipulators of host cells
Y Rikihisa |
Nature Reviews Microbiology | 2010 |
Anaplasma phagocytophilum AptA modulates Erk1/2 signaling
B Sukumaran, JE Mastronunzio, S Narasimhan, S Fankhauser, PD Uchil, R Levy, M Graham, TM Colpitts, CF Lesser, E Fikrig |
Cellular Microbiology | 2010 |
The Anaplasma phagocytophilum-occupied vacuole selectively recruits Rab-GTPases that are predominantly associated with recycling endosomes
B Huang, A Hubber, JA McDonough, CR Roy, MA Scidmore, JA Carlyon |
Cellular Microbiology | 2010 |
Anaplasma phagocytophilum APH_0032 is expressed late during infection and localizes to the pathogen-occupied vacuolar membrane
B Huang, MJ Troese, D Howe, S Ye, JT Sims, RA Heinzen, DL Borjesson, JA Carlyon |
Microbial Pathogenesis | 2010 |
Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases
VG Fowler, WM Scheld, AS Bayer |
Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases | 2010 |
Type IV secretion in the obligatory intracellular bacterium Anaplasma phagocytophilum
Y Rikihisa, M Lin, H Niu |
Cellular Microbiology | 2010 |
Anaplasma phagocytophilum APH_1387 Is Expressed throughout Bacterial Intracellular Development and Localizes to the Pathogen-Occupied Vacuolar Membrane
B Huang, MJ Troese, S Ye, JT Sims, NL Galloway, DL Borjesson, JA Carlyon |
Infection and immunity | 2010 |
Autophagy in Infection and Immunity
B Levine, T Yoshimori, V Deretic |
2009 | |
Autophagy in Infection and Immunity
B Levine, T Yoshimori, V Deretic |
2009 | |
Autophagy in Infection and Immunity
B Levine, T Yoshimori, V Deretic |
2009 | |
Autophagy in Infection and Immunity
B Levine, T Yoshimori, V Deretic |
2009 | |
Autophagy in Infection and Immunity
B Levine, T Yoshimori, V Deretic |
2009 | |
Autophagy in Infection and Immunity
B Levine, T Yoshimori, V Deretic |
2009 | |
Autophagy in Infection and Immunity
B Levine, T Yoshimori, V Deretic |
2009 | |
Autophagy in Infection and Immunity
B Levine, T Yoshimori, V Deretic |
2009 | |
Autophagy in Infection and Immunity
B Levine, T Yoshimori, V Deretic |
2009 | |
Autophagy in Infection and Immunity
B Levine, T Yoshimori, V Deretic |
2009 | |
Autophagy in intracellular bacterial infection
E Campoy, MI Colombo |
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2009 |
Anaplasma phagocytophilum Dense-Cored Organisms Mediate Cellular Adherence through Recognition of Human P-Selectin Glycoprotein Ligand 1
MJ Troese, JA Carlyon |
Infection and immunity | 2009 |
Neutrophil apoptosis and the resolution of infection
AD Kennedy, FR DeLeo |
Immunologic Research | 2008 |
Subversion of cellular autophagy by Anaplasma phagocytophilum
H Niu, M Yamaguchi, Y Rikihisa |
Cellular Microbiology | 2008 |
Immune evasion and immunosuppression by Anaplasma phagocytophilum, the causative agent of tick-borne fever of ruminants and human granulocytic anaplasmosis
Z Woldehiwet |
The Veterinary Journal | 2008 |
Ehrlichioses et anaplasmoses humaines
S Rebaudet, P Brouqui |
EMC - Maladies Infectieuses | 2008 |
Anaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection
V Thomas, E Fikrig |
Cellular Microbiology | 2007 |
Anaplasma phagocytophilum AnkA is tyrosine-phosphorylated at EPIYA motifs and recruits SHP-1 during early infection
JW IJdo, AC Carlson, EL Kennedy |
Cellular Microbiology | 2007 |
Isolation and Establishment of the RaccoonEhrlichia-Like Agent in Tick Cell Culture
UG Munderloh, MJ Yabsley, SM Murphy, MP Luttrell, EW Howerth |
Vector-Borne and Zoonotic Diseases | 2007 |
An Ixodes scapularis protein required for survival of Anaplasma phagocytophilum in tick salivary glands
B Sukumaran, S Narasimhan, JF Anderson, K DePonte, N Marcantonio, MN Krishnan, D Fish, SR Telford, FS Kantor, E Fikrig |
Journal of Experimental Medicine | 2006 |
Infectious Disease and Therapy
A Tselis |
Epstein-Barr Virus | 2006 |
Differential expression of VirB9 and VirB6 during the life cycle of Anaplasma phagocytophilum in human leucocytes is associated with differential binding and avoidance of lysosome pathway
H Niu, Y Rikihisa, M Yamaguchi, N Ohashi |
Cellular Microbiology | 2006 |
Dissociation between Inhibition and Killing by Levofloxacin in Human Granulocytic Anaplasmosis
GP Wormser, A Filozov, SR Telford, S Utpat, RS Kamer, D Liveris, G Wang, L Zentmaier, I Schwartz, ME Aguero-Rosenfeld |
Vector-Borne and Zoonotic Diseases | 2006 |
Anaplasma phagocytophilum Modulates gp91 phox Gene Expression through Altered Interferon Regulatory Factor 1 and PU.1 Levels and Binding of CCAAT Displacement Protein
V Thomas, S Samanta, C Wu, N Berliner, E Fikrig |
Infection and immunity | 2005 |
Human Granulocytic Anaplasmosis and Anaplasma phagocytophilum
JS Dumler, KS Choi, JC Garcia-Garcia, NS Barat, DG Scorpio, JW Garyu, DJ Grab, JS Bakken |
Emerging infectious diseases | 2005 |
Tick-Borne Diseases of Humans
JL Goodman, DT Dennis, DE Sonenshine |
2005 | |
Defective Phagocytosis in Anaplasma phagocytophilum - Infected Neutrophils
JW Garyu, K Choi, DJ Grab, JS Dumler |
Infection and immunity | 2005 |
Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection
B Sukumaran, JA Carlyon, JL Cai, N Berliner, E Fikrig |
Infection and immunity | 2005 |
Insights into Pathogen Immune Evasion Mechanisms: Anaplasma phagocytophilum Fails to Induce an Apoptosis Differentiation Program in Human Neutrophils
DL Borjesson, SD Kobayashi, AR Whitney, JM Voyich, CM Argue, FR DeLeo |
Journal of immunology (Baltimore, Md. : 1950) | 2005 |
Molecular diagnosis of human granulocytic anaplasmosis
JS Dumler, P Brouqui |
Expert Review of Molecular Diagnostics | 2004 |
Characteristic peripheral blood findings in human ehrlichiosis
KS Hamilton, SM Standaert, MC Kinney |
Modern Pathology | 2004 |
Anaplasma phagocytophilum Utilizes Multiple Host Evasion Mechanisms To Thwart NADPH Oxidase-Mediated Killing during Neutrophil Infection
JA Carlyon, DA Latif, M Pypaert, P Lacy, E Fikrig |
Infection and immunity | 2004 |
Evaluation of Antibiotic Susceptibilities of Ehrlichia canis , Ehrlichia chaffeensis , and Anaplasma phagocytophilum by Real-Time PCR
S Branger, JM Rolain, D Raoult |
Antimicrobial agents and chemotherapy | 2004 |
Neutrophil NADPH Oxidase Is Reduced at the Anaplasma phagocytophilum Phagosome
JW IJdo, AC Mueller |
Infection and immunity | 2004 |
Ehrlichia chaffeensis and Anaplasma phagocytophilum lack genes for lipid A biosynthesis and incorporate cholesterol for their survival
M Lin, Y Rikihisa |
Infection and immunity | 2003 |
Invasion and survival strategies ofAnaplasma phagocytophilum
JA Carlyon, E Fikrig |
Cellular Microbiology | 2003 |
Mechanisms of pathogenesis: evasion of killing by polymorphonuclear leukocytes
LA Allen |
Microbes and Infection | 2003 |
Obligatory intracellular parasitism byEhrlichia chaffeensisandAnaplasma phagocytophiluminvolves caveolae and glycosylphosphatidylinositol-anchored proteins
M Lin, Y Rikihisa |
Cellular Microbiology | 2003 |
THECHLAMYDIALINCLUSION: Escape from the Endocytic Pathway1
KA Fields, T Hackstadt |
Annual Review of Cell and Developmental Biology | 2002 |
Exploitation of interleukin-8-induced neutrophil chemotaxis by the agent of human granulocytic ehrlichiosis
M Akkoyunlu, SE Malawista, J Anguita, E Fikrig |
Infection and immunity | 2001 |
Intracellular Parasitism by the Human Granulocytic Ehrlichiosis Bacterium Through the P-Selectin Ligand, PSGL-1
MJ Herron, CM Nelson, J Larson, KR Snapp, GS Kansas, JL Goodman |
Science | 2000 |
Persistent Bacterial Infections
JP Nataro, MJ Blaser, S Cunningham-Rundles |
2000 | |
Granulocytic Ehrlichiosis in Mice Deficient in Phagocyte Oxidase or Inducible Nitric Oxide Synthase
RN Moore, R Banerjee, J Anguita, E Fikrig |
Infection and immunity | 2000 |
Characterization and intracellular trafficking pattern of vacuoles containing Chlamydia pneumoniae in human epithelial cells
HM Al-Younes, T Rudel, TF Meyer |
Cellular Microbiology | 1999 |
Ehrlichia chaffeensis and E. sennetsu , but Not the Human Granulocytic Ehrlichiosis Agent, Colocalize with Transferrin Receptor and Up-Regulate Transferrin Receptor mRNA by Activating Iron-Responsive Protein 1
PE Orndorff, RE Barnewall, N Ohashi, Y Rikihisa |
Infection and immunity | 1999 |
Cloning, expression, and localization of a novel γ-adaptin-like molecule
DA Lewin, D Sheff, CE Ooi, JA Whitney, E Yamamoto, LM Chicione, P Webster, JS Bonifacino, I Mellman |
FEBS Letters | 1998 |