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19. Tick Saliva and Salivary Glands: What Do We Know So Far on Their Role in Arthropod Blood Feeding and Pathogen Transmission

Author

Neelakanta, Girish and Sultana, Hameeda

Subjects
Microbiology (medical), cement, saliva, Immunology, Review, exosomes, vaccines, bacterial infections and mycoses, Microbiology, Salivary Glands, QR1-502, ticks, Cellular and Infection Microbiology, Infectious Diseases, HSP70s, parasitic diseases, Animals, OATPs, Salivary Proteins and Peptides, Arthropods, histamines
Abstract

Ticks are blood-sucking arthropods that have developed myriad of strategies to get a blood meal from the vertebrate host. They first attach to the host skin, select a bite site for a blood meal, create a feeding niche at the bite site, secrete plethora of molecules in its saliva and then starts feeding. On the other side, host defenses will try to counter-attack and stop tick feeding at the bite site. In this constant battle between ticks and the host, arthropods successfully pacify the host and completes a blood meal and then replete after full engorgement. In this review, we discuss some of the known and emerging roles for arthropod components such as cement, salivary proteins, lipocalins, HSP70s, OATPs, and extracellular vesicles/exosomes in facilitating successful blood feeding from ticks. In addition, we discuss how tick-borne pathogens modulate(s) these components to infect the vertebrate host. Understanding the biology of arthropod blood feeding and molecular interactions at the tick-host interface during pathogen transmission is very important. This information would eventually lead us in the identification of candidates for the development of transmission-blocking vaccines to prevent diseases caused by medically important vector-borne pathogens.

Published
2022
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22. Anaplasma phagocytophilum induces Ixodes scapularis ticks to express an antifreeze glycoprotein gene that enhances their survival in the cold

Author

Neelakanta, Girish, Sultana, Hameeda, Fish, Durland, Anderson, John F., and Fikrig, Erol

Subjects
Glycoproteins -- Properties -- Genetic aspects -- Physiological aspects, Gene expression -- Physiological aspects -- Genetic aspects, Adaptation (Physiology) -- Genetic aspects -- Physiological aspects, Gram-negative bacteria -- Genetic aspects -- Physiological aspects, Health care industry
Abstract

In the United States, Ixodes scapularis ticks overwinter in the Northeast and Upper Midwest and transmit the agent of human granulocytic anaplasmosis, Anaplasma phagocytophilum, among other pathogens. We now show that the presence of A. phagocytophilum in I. scapularis ticks increases their ability to survive in the cold. We identified an I. scapularis antifreeze glycoprotein, designated IAFGP, and demonstrated via RNAi knockdown studies the importance of IAFGP for the survival of I. scapularis ticks in a cold environment. Transfection studies also show that IAFGP increased the viability of yeast cells subjected to cold temperature. Remarkably, A. phagocytophilum induced the expression of iafgp, thereby increasing the cold tolerance and survival of I. scapularis. These data define a molecular basis for symbiosis between a human pathogenic bacterium and its arthropod vector and delineate what we believe to be a new pathway that may be targeted to alter the life cycle of this microbe and its invertebrate host., Introduction Diverse arthropods have intimate relationships with microbes (1-5). Several examples include pheromonal symbiosis of desert locusts (6) and nutritional symbiosis of flower thrips (7) with environmentally acquired bacteria. Aphid-Buchnera [...]

Published
2010
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26. RNA interference screen for human genes associated with West Nile virus infection

Author

Krishnan, Manoj N., Ng, Aylwin, Sukumaran, Bindu, Gilfoy, Felicia D., Uchil, Pradeep D., Sultana, Hameeda, Brass, Abraham L., Adametz, Rachel, Tsui, Melody, Qian, Feng, Montgomery, Ruth R., Lev, Sima, Mason, Peter W., Koski, Raymond A., Elledge, Stephen J., Xavier, Ramnik J., Agaisse, Herve, and Fikrig, Erol

Subjects
West Nile virus -- Genetic aspects -- Usage -- Research, Viral proteins -- Identification and classification -- Research -- Genetic aspects -- Usage, Environmental issues, Science and technology, Zoology and wildlife conservation, Identification and classification, Usage, Genetic aspects, Research
Abstract

West Nile virus (WNV), and related flaviviruses such as tick-borne encephalitis, Japanese encephalitis, yellow fever and dengue viruses, constitute a significant global human health problem (1). However, our understanding of [...]

Published
2008

32. Meeting Abstracts of the American Society for Exosomes and Microvesicles 2020 Annual Meeting

Author

Weaver, Alissa M., primary, McNamara, Ryan P., additional, Loh, Y Peng, additional, McMillan, Hannah M., additional, Rodriguez, Blanca V., additional, Erickson, James, additional, Branscome, Heather, additional, Sharif, Sarah Al, additional, Mishra, Ribhav, additional, Lennon, Kathleen M, additional, Lee, Amy H., additional, Lee, Jean C., additional, Ratitong, Bridget, additional, Pullan, Jessica, additional, Hood, Joshua L., additional, Khatkar, Pooja, additional, Zempleni, Janos, additional, Zhao, Yi, additional, Comfort, Nicole, additional, Pavlic, Jordan, additional, Hooten, Nicole Noren, additional, Andres, Sarah F., additional, Meyer, Lisa, additional, Sharma, Shivani, additional, Akers, Johnny, additional, Perin, Laura, additional, Purcell, Emma, additional, Sass, Dilorom, additional, Kurihara, Tatsuo, additional, Gupta, Shamba, additional, Nakase, Ikuhiko, additional, Cowen, Maria, additional, Kim, Yuriy, additional, Reshke, Ryan, additional, Ikezu, Tsuneya, additional, Sultana, Hameeda, additional, O’Brien, Killian P., additional, Nwokwu, Chukwumaobim D., additional, Zuhorn, Inge S., additional, Carding, Simon, additional, Steindler, Dennis A., additional, Verweij, Frederik J., additional, Vader, Pieter, additional, Olivier, Martin, additional, D’Souza-Schorey, Crislyn, additional, and Amit, Moran, additional

Published
2020
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36. Tick-Borne Flavivirus Inhibits Sphingomyelinase (Is SMase), a Venomous Spider Ortholog to Increase Sphingomyelin Lipid Levels for Its Survival in Ixodes scapularis Ticks.

Author

Regmi, Pravesh, Khanal, Supreet, Neelakanta, Girish, and Sultana, Hameeda

Subjects
IXODES scapularis, SPHINGOMYELIN, EXTRACELLULAR vesicles, TICKS, TICK-borne encephalitis viruses
Abstract

Our previous study showed that cells from medically important arthropods, such as ticks, secrete extracellular vesicles (EVs) including exosomes that mediate transmission of flavivirus RNA and proteins to the human cells. Understanding the molecular determinants and mechanism(s) of arthropod-borne flavivirus transmission via exosome biogenesis is very important. In this current study, we showed that in the presence of tick-borne Langat Virus (LGTV; a member of tick-borne encephalitis virus complex), the expression of arthropod Is SMase, a sphingomyelinase D (SMase D) that catalyzes the hydrolytic cleavage of substrates like sphingomyelin (SM) lipids, was significantly reduced in both Ixodes scapularis ticks (in vivo) and in tick cells (in vitro). The Is SMase reduced levels correlated with down-regulation of its activity upon LGTV replication in tick cells. Our data show that LGTV-mediated suppression of Is SMase allowed accumulation of SM lipid levels that supported membrane-associated viral replication and exosome biogenesis. Inhibition of viral loads and SM lipid built up upon GW4869 inhibitor treatment reversed the Is SMase levels and restored its activity. Our results suggest an important role for this spider venomous ortholog Is SMase in regulating viral replication associated with membrane-bound SM lipids in ticks. In summary, our study not only suggests a novel role for arthropod Is SMase in tick-LGTV interactions but also provides new insights into its important function in vector defense mechanism(s) against tick-borne virus infection and in anti-viral pathway(s). [ABSTRACT FROM AUTHOR]

Published
2020
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38. Coordination of different ligands to copper(II) and cobalt(III) metal centers enhances Zika virus and dengue virus loads in both arthropod cells and human keratinocytes

Author

Dutta, Shovan, primary, Celestine, Michael J., additional, Khanal, Supreet, additional, Huddleston, Alexis, additional, Simms, Colin, additional, Arca, Jessa Faye, additional, Mitra, Amlan, additional, Heller, Loree, additional, Kraj, Piotr J., additional, Ledizet, Michel, additional, Anderson, John F., additional, Neelakanta, Girish, additional, Holder, Alvin A., additional, and Sultana, Hameeda, additional

Published
2018
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43. Ixodes scapularisSrc tyrosine kinase facilitates Anaplasma phagocytophilumsurvival in its arthropod vector

Author

Turck, Jeremy W., Taank, Vikas, Neelakanta, Girish, and Sultana, Hameeda

Abstract

Anaplasma phagocytophilum,the agent of human anaplasmosis, is an obligate intracellular bacterium that uses multiple survival strategies to persist in Ixodes scapularisticks. Our previous study showed that A. phagocytophilumefficiently induced the tyrosine phosphorylation of several Ixodesproteins that includes extended phosphorylation of actin at tyrosine residue Y178. In order to identify the tyrosine kinase responsible for the A. phagocytophiluminduced tyrosine phosphorylation of proteins, we combed the I. scapularisgenome and identified a non-receptor Src tyrosine kinase ortholog. I. scapularisSrc kinase showed high degree of amino acid sequence conservation with Dsrc from Drosophila melanogaster. We noted that at different developmental stages of I. scapularisticks, larvae expressed significantly higher levels of srctranscripts in comparison to the other stages. We found that A. phagocytophilumsignificantly reduced Src levels in unfed nymphs and in nymphs while blood feeding (48 h during feeding) in comparison to the levels noted to relative uninfected controls. However, A. phagocytophilumincreased Src levels in fully engorged larvae and nymphs (48 h post feeding) and in vitrotick cells in comparison to the relative uninfected controls. Inhibition of Src kinase expression and activity by treatment with src-dsRNA or Src-inhibitor, respectively, significantly reduced A. phagocytophilumloads in ticks and tick cells. Overall, our study provides evidence for the important role of I. scapularisSrc kinase in facilitating A. phagocytophilumcolonization and survival in the arthropod vector.

Published
2019
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45. Cyclase associated protein CAP in the regulation of the actin cytoskeleton and cell polarity in Dictyostelium discoideum

Author

Sultana, Hameeda

Subjects
ddc:570, macromolecular substances
Abstract

Dictyostelium discoideum amoebae offer great opportunities to elucidate the signalling pathways involved in the generation of cell polarity. They constantly change their shape and form new ends in response to a plethora of environmental signals. This process requires distinct signalling molecules, the chemotactic machinery and components of the cytoskeleton such as CAP, which in Dictyostelium is involved in actin cytoskeleton rearrangements. Dictyostelium cells deficient for CAP show a defect in cell polarization during development and an altered cAMP relay response. In this work we wanted to study the position of CAP in the signalling network and made use of mutants defective in components of cAMP signalling (ACA, cAR1/3, G-alpha2, G-beta, PI3-kinase, Pianissimo and PKA) in which we studied CAP and CAP associated responses. Our studies revealed that CAP functions independent of ACA, cAR1/3, G-alpha2, G-beta, PI3-kinase and Pianissimo whereas the cAMP dependent protein kinase A (PKA) is necessary for targeting CAP to the sites of its cellular action. The localization data suggest that CAP and PKA may functionally co-operate to control actin organization and cell polarity. We further observed that CAP functions downstream of PI3-kinases or in parallel pathways because overexpression of CAP rescued the severe impairment in pinocytosis in the pik1-/2- cells, their altered distribution of F-actin and also the abnormal developmental phenotypes. In line with this proposal CAP could partially rescue the phagocytosis defect of the g-beta cells. CAP expression also improved the development of aggregation deficient aca- cells but did not lead to complete restoration. The cell polarity and streaming defects of aca- cells were also rescued by the moderate expression of CAP making CAP a molecule downstream in the hierarchy of the signal transduction cascade. On the other hand, CAP regulates LimD, a component of the actin cytoskeleton which in Dictyostelium is involved in generation of cell polarity as shown by an altered behaviour of GFP-LimD in CAP bsr cells in comparison to wild type. To gain more insight into the in vivo functioning of CAP, we performed a search for binding partners which suggested that CAP associates and interacts with the vacuolar ATPases complex, and that the absence of CAP disrupts the vacuolar network. This underlines the findings obtained in the PI3-kinase mutants that CAP is a general regulator of endocytosis. We also identified ARP2/3 complex p34-ARC subunit, Rab4, Rab11 and porin as potential interacting partners of CAP by biochemical methods. The significance of this interaction is under investigation. Finally, our microarray analysis suggested that in the absence of CAP the actin cytoskeleton and signalling machinery is strongly affected. The up-regulation of regA (negative regulator of intracellular cAMP), and kinases like erk1, statA and pakA might be of relevance for the altered cAMP relay of CAP bsr cells. The repression of the expression of cytoskeletal components like profilins I and II, villidin, coactosin, myosin and signalling molecules like NDP kinases

Published
2004

47. Antivirulence Properties of an Antifreeze Protein

Author

Heisig, Martin, primary, Abraham, Nabil M., additional, Liu, Lei, additional, Neelakanta, Girish, additional, Mattessich, Sarah, additional, Sultana, Hameeda, additional, Shang, Zhengling, additional, Ansari, Juliana M., additional, Killiam, Charlotte, additional, Walker, Wendy, additional, Cooley, Lynn, additional, Flavell, Richard A., additional, Agaisse, Herve, additional, and Fikrig, Erol, additional

Published
2014
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