Two Kinds of Ferritin Protect Ixodid Ticks from Iron Overload and Consequent Oxidative Stress

Galay, Remil Linggatong; Umemiya‐Shirafuji, Rika; Bacolod, Eugene T.; Maeda, Hiroki; Kusakisako, Kodai; Koyama, Jiro; Tsuji, Naotoshi; Mochizuki, Masahito; Fujisaki, Kozo; Tanaka, Tetsuya

doi:10.1371/journal.pone.0090661

Cited by 51 publications

(40 citation statements)

References 40 publications

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“…In addition to the role of storage in mammals, insect ferritins have shown to assist in iron transport (Pham and Winzerling, 2010). Ferritin has been previously identified in several tick species including Ornithodoros moubata , Ixodes ricinus , H. longicornis and R. microplus (Galay et al, 2014; Hajdusek et al, 2010; Kopáček et al, 2003). Silencing of ferritin has demonstrated negative effects on tick feeding and tick reproduction (Galay et al, 2013, 2014).…”

Section: Resultsmentioning

confidence: 99%

“…Ferritin has been previously identified in several tick species including Ornithodoros moubata , Ixodes ricinus , H. longicornis and R. microplus (Galay et al, 2014; Hajdusek et al, 2010; Kopáček et al, 2003). Silencing of ferritin has demonstrated negative effects on tick feeding and tick reproduction (Galay et al, 2013, 2014). Immunization trials against ferritin where tick infestations were reduced indicate that tick ferritins are essential for successful feeding (Hajdusek et al, 2010).…”

Section: Resultsmentioning

confidence: 99%

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Identification of 24h Ixodes scapularis immunogenic tick saliva proteins

Lewis

Radulović

Kim

et al. 2015

Ticks and Tick-borne Diseases

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Ixodes scapularis is arguably the most medically important tick species in the United States. This tick transmits 5 of the 14 human tick-borne disease (TBD) agents in the USA: Borrelia burgdorferi, Anaplasma phagocytophilum, B. miyamotoi, Babesia microti, and Powassan virus disease. Except for the Powassan virus disease, I. scapularis-vectored TBD agents require more than 24 h post attachment to be transmitted. This study describes identification of 24 h immunogenic I. scapularis tick saliva proteins, which could provide opportunities to develop strategies to stop tick feeding before transmission of the majority of pathogens. A 24 h fed female I. scapularis phage display cDNA expression library was biopanned using rabbit antibodies to 24 h fed I. scapularis female tick saliva proteins, subjected to next generation sequencing, de novo assembly, and bioinformatic analyses. A total of 182 contigs were assembled, of which ~19% (35/182) are novel and did not show identity to any known proteins in GenBank. The remaining ~81% (147/182) of contigs were provisionally identified based on matches in GenBank including ~18% (27/147) that matched protein sequences previously annotated as hypothetical and putative tick saliva proteins. Others include proteases and protease inhibitors (~3%, 5/147), transporters and/or ligand binding proteins (~6%, 9/147), immunogenic tick saliva housekeeping enzyme-like (17%, 25/147), ribosomal protein-like (~31%, 46/147), and those classified as miscellaneous (~24%, 35/147). Notable among the miscellaneous class include antimicrobial peptides (microplusin and ricinusin), myosin-like proteins that have been previously found in tick saliva, and heat shock tick saliva protein. Data in this study provides the foundation for in-depth analysis of I. scapularis feeding during the first 24 h, before the majority of TBD agents can be transmitted.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Identification of 24h Ixodes scapularis immunogenic tick saliva proteins

Lewis

Radulović

Kim

et al. 2015

Ticks and Tick-borne Diseases

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“…RNAi is a good technique for screening candidate antigens for vaccine development [12]. Our previous gene silencing studies showed that HlFERs are crucial to the blood feeding and reproduction of H. longicornis [17], providing protection against ironmediated oxidative stress [18] and making them good candidate vaccine antigens. Our vaccination experiments showed that both rHlFER1 and rHlFER2 are highly immunogenic, inducing host antibody production.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous studies on two ferritins of the hard tick H. longicornis using RNAi showed that both are physiologically important in blood feeding and reproduction [17] by preventing iron overload and the occurrence of oxidative stress [18]. Furthermore, a previous study showed that FER2 vaccination had considerable effects on infestation of I. ricinus and R. microplus [19].…”

Section: Discussionmentioning

confidence: 99%

Evaluation and comparison of the potential of two ferritins as anti-tick vaccines against Haemaphysalis longicornis

et al. 2014

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Background: Tick control is an essential aspect of controlling the spread of tick-borne diseases affecting humans and animals, but it presently faces several challenges. Development of an anti-tick vaccine is aimed at designing cost-effective and environmentally friendly protection against ticks and tick-borne diseases as an alternative to the use of chemical acaricides. A single vaccine from the tick midgut protein Bm86 is currently available for field applications, but its efficacy is limited to only some tick species. Identification of candidate vaccine antigens that can affect multiple tick species is highly desirable. The hard tick Haemaphysalis longicornis has two kinds of the iron-binding protein ferritin (HlFER), an intracellular HlFER1 and a secretory HlFER2, and RNA interference experiments showed that these are physiologically important in blood feeding and reproduction and in protection against oxidative stress. Here we investigated the potential of targeting HlFERs for tick control by immunizing the host with recombinant HlFERs (rHlFER1 and rHlFER2).Methods: Rabbits were immunized with rHlFERs three times subcutaneously at two-week intervals. Antisera were collected before the first immunization and a week after each immunization to confirm the antigen-specific serum antibody titer by serum ELISA. Two weeks after the final immunization, the rabbits were challenged with tick infestation. After dropping, tick feeding and reproduction parameters were evaluated to determine vaccine efficacy. To demonstrate the effects of antibodies, oxidative stress was detected in the eggs and larvae.Results: The antibody titer of rHlFER-immunized rabbits greatly increased after the second immunization. Antibodies exhibited cross-reactivity with rHlFERs and reacted with tick native HlFERs in Western blot analysis. Significantly lower bodyweight was observed in the ticks infested from the rHlFER2-immunized rabbit compared to those from the control rabbit. Reduced oviposition and hatching rate were observed in both rHlFER-immunized groups. rHlFER2 showed a higher vaccine efficacy. The antibodies against rHlFERs were detected in the eggs, and higher levels of oxidative stress biomarkers in the eggs and larvae, of ticks from rHlFER vaccinated rabbits. Conclusion:Collectively, these results showed that HlFER2 has a good potential as an anti-tick vaccine antigen that may affect multiple tick species.

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“…Silencing two types of the iron storage protein ferritin greatly reduced the ticks' capacity to engorge and produce eggs, also affecting post-blood meal survival due to occurrence of iron-mediated oxidative stress [113]. An iron regulatory protein responsible for translation of iron binding proteins was characterized in I. scapularis, with its knockdown greatly reducing egg hatchability [111].…”

Section: Genes Related To Structural and Metabolic Functionsmentioning

confidence: 99%

RNA Interference – A Powerful Functional Analysis Tool for Studying Tick Biology and its Control

Galay¹,

Umemiya‐Shirafuji²,

MasamiMochizuki³

et al. 2016

RNA Interference

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Ticks (Acari: Ixodida) are blood-sucking arthropods globally recognized as vectors of numerous diseases. They are primarily responsible for the transmission of various pathogens, including viruses, rickettsiae, and blood parasites of animals. Ticks are second to mosquitoes in terms of disease transmission to humans. The continuous emergence of tick-borne diseases and acaricide resistance of ticks necessitates the development of new and more effective control agents and strategies; therefore, understanding of different aspects of tick biology and their interaction with pathogens is very crucial in developing effective control strategies. RNA interference (RNAi) has been widely used in the area of tick research as a versatile reverse genetic tool to elucidate the functions of various tick proteins. During the past decade, numerous studies on ticks utilized RNAi to evaluate potentially key tick proteins involved in blood feeding, reproduction, evasion of host immune response, interaction with pathogens, and pathogen transmission that may be targeted for tick and pathogen control. This chapter reviewed the application of RNAi in tick research over the past decade, focusing on the impact of this technique in the advancement of knowledge on tick and pathogen biology.

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Two Kinds of Ferritin Protect Ixodid Ticks from Iron Overload and Consequent Oxidative Stress

Cited by 51 publications

References 40 publications

Identification of 24h Ixodes scapularis immunogenic tick saliva proteins

Identification of 24h Ixodes scapularis immunogenic tick saliva proteins

Evaluation and comparison of the potential of two ferritins as anti-tick vaccines against Haemaphysalis longicornis

RNA Interference – A Powerful Functional Analysis Tool for Studying Tick Biology and its Control

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