Roles of Tick Symbiotic Microorganisms in Pathogen Transmission

Abstract

Ticks have garnered significant research interest owing to their ability to vector pathogens into humans and animals. The intricate symbiotic associations between ticks and tick microbiota substantially influence developmental processes, reproductive success, and potential to serve as vectors for tick-transmitted diseases. This paper reviews the epidemiology of diseases transmitted by ticks and delves into the composition and function of tick endosymbionts in transmission and infection. This review also highlights the role of tick immunity in maintaining gut homeostasis. Finally, tick symbiont-pathogen interactions and potential strategies for controlling tick-borne diseases by leveraging symbiotic relationships are discussed.

Keywords

tick / tick-borne pathogens / endosymbionts / symbiont-pathogen interactions / tick control strategies

References

[1] Min P, Song J, Zhao S. Tick species, tick-borne pathogen distribution and risk factor analysis in border areas of China, Russia and North Korea. Front Vet Sci. 2025; 12: 1529253.

[2] Shah T, Li Q, Wang B, Baloch Z, Xia X. Geographical distribution and pathogenesis of ticks and tick-borne viral diseases. Front Microbiol. 2023; 14: 1185829.

[3] Yang H, Gould CA, Jones R, St Juliana A, Sarofim M, Rissing M, et al. By-degree health and economic impacts of Lyme disease, Eastern and Midwestern United States. Ecohealth. 2024; 1: 56-70.

[4] Wimms C, Aljundi E, Halsey SJ. Regional dynamics of tick vectors of human disease. Curr Opin Insect Sci. 2023; 55: 101006.

[5] Luo YF, Li SQ. Indian monsoon drove the dispersal of the thoracica group of Scytodes spitting spiders . Zool Res. 2024; 1: 152-159.

[6] Zhang MZ, Bian C, Ye RZ, Cui XM, Yao NN, Yang JH, et al. A series of patients infected with the emerging tick-borne Yezo virus in China: an active surveillance and genomic analysis. Lancet Infect Dis. 2024; 25(4): 390-398.

[7] Bakker JW, Esser HJ, Sprong H, Godeke GJ, Hoornweg TE, de Boer WF, et al. Differential susceptibility of geographically distinct Ixodes ricinus populations to tick-borne encephalitis virus and louping ill virus . Emerg Microbes Infect. 2024; 13(1): 2321992.

[8] Tang X, Cui Y, Namarra U, Tian X, Rivas-Giorgi F, Fikrig E. Dual roles for a tick protein disulfide isomerase during the life cycle of the Lyme disease agent. mBio. 2024; 15(12): e0175424.

[9] Jia N, Wang J, Shi W, Du L, Sun Y, Zhan W, et al. Large-scale comparative analyses of tick genomes elucidate their genetic diversity and vector capacities. Cell. 2020; 5: 1328-1340.e1313.

[10] Melo CL, Mageste LR, Guaraldo L, Paula DP, Wakimoto MD. Use of digital tools in arbovirus surveillance: scoping review. J Med Internet Res. 2024; 26: e57476.

[11] Rowan S, Mohseni N, Chang M, Burger H, Peters M, Mir S. From tick to test: a comprehensive review of tick-borne disease diagnostics and surveillance methods in the United States. Life (Basel). 2023; 13(10): 2048.

[12] de la Fuente J, Antunes S, Bonnet S, Cabezas-Cruz A, Domingos AG, Estrada-Peña A, et al. Tick-pathogen interactions and vector competence: identification of molecular drivers for tick-borne diseases. Front Cell Infect Microbiol. 2017; 77: 114.

[13] Hajdušek O, Síma R, Ayllón N, Jalovecká M, Perner J, de la Fuente J, et al. Interaction of the tick immune system with transmitted pathogens. Front Cell Infect Microbiol. 2013; 3: 26.

[14] Zhong Z, Wang K, Wang J. Tick symbiosis. Curr Opin Insect Sci. 2024; 62: 101163.

[15] Elston KM, Leonard SP, Geng P, Bialik SB, Robinson E, Barrick JE. Engineering insects from the endosymbiont out. Trends Microbiol. 2022; 30(1): 79-96.

[16] Wang J, Gao L, Aksoy S. Microbiota in disease-transmitting vectors. Nat Rev Microbiol. 2023; 9: 604-618.

[17] Guizzo MG, Tirloni L, Gonzalez SA, Farber MD, Braz G, Parizi LF, et al. Coxiella endosymbiont of Rhipicephalus microplus modulates tick physiology with a major impact in blood feeding capacity . Front Microbiol. 2022; 13: 868575.

[18] Samaddar S, Rolandelli A, O’Neal AJ, Laukaitis-Yousey HJ, Marnin L, Singh N, et al. Bacterial reprogramming of tick metabolism impacts vector fitness and susceptibility to infection. Nat Microbiol. 2024; 9: 2278-2291.

[19] Duron O. Nutritional symbiosis in ticks: singularities of the genus Ixodes. Trends Parasitol. 2024; 8: 696-706.

[20] Buysse M, Floriano AM, Gottlieb Y, Nardi T, Comandatore F, Olivieri E, et al. A dual endosymbiosis supports nutritional adaptation to hematophagy in the invasive tick Hyalomma marginatum . Elife. 2021; 10: e72747.

[21] Cibichakravarthy B, Shaked N, Kapri E, Gottlieb Y. Endosymbiont-derived metabolites are essential for tick host reproductive fitness. mSphere. 2024; 9(7): e0069323.

[22] Zhang YK, Li SS, Yang C, Zhang YF, Zhang XY, Liu JZ. Tetracycline inhibits tick host reproduction by modulating bacterial microbiota, gene expression and metabolism levels. Pest Manag Sci. 2024; 80(2): 366-375.

[23] Hayes BM, Radkov AD, Yarza F, Flores S, Kim J, Zhao Z, et al. Ticks resist skin commensals with immune factor of bacterial origin. Cell. 2020; 183(6): 1562-1571.e1512.

[24] Hussain S, Perveen N, Hussain A, Song B, Aziz MU, Zeb J, et al. The symbiotic continuum within ticks: opportunities for disease control. Front Microbiol. 2022; 13: 854803.

[25] Sun Y, Chen C, Zeng C, Xia Q, Yuan C, Pei H. Severe fever with thrombocytopenia syndrome virus infection shapes gut microbiome of the tick vector Haemaphysalis longicornis . Parasit Vectors. 2024; 1: 107.

[26] Mazuecos L, González-García A, de la Fuente J. Genetic modification, characterization, and co-infection of Franken Sphingomonas and Anaplasma phagocytophilum in tick cells . STAR Protoc. 2023; 4(3): 102557.

[27] Mazuecos L, Alberdi P, Hernández-Jarguín A, Contreras M, Villar M, Cabezas-Cruz A, et al. Frankenbacteriosis targeting interactions between pathogen and symbiont to control infection in the tick vector. iScience. 2023; 26(5): 106697.

[28] Liu MC, Zhang JT, Chen JJ, Zhu Y, Fu BK, Hu ZY, et al. A global dataset of microbial community in ticks from metagenome study. Sci Data. 2022; 9(1): 560.

[29] Liu Q, Yang K, Xie B, Gao Y, Xu S, Lu Y. Mapping structural variations in Haemaphysalis longicornis and Rhipicephalus microplus reveals vector-pathogen adaptation . iScience. 2023; 26(4): 106398.

[30] Yu Z, Wang H, Wang T, Sun W, Yang X, Liu J. Tick-borne pathogens and the vector potential of ticks in China. Parasit Vectors. 2015; 8: 24.

[31] Leventhal SS, Bisom T, Clift D, Rao D, Meade-White K, Shaia C, et al. Antibodies targeting the Crimean-Congo hemorrhagic fever virus nucleoprotein protect via TRIM21. Nat Commun. 2024; 15(1): 9236.

[32] Zhang X, Zhao C, Si X, Hu Q, Zheng A. Natural circulation of tick-borne severe fever with thrombocytopenia syndrome virus in the city ecosystem, China. Virol Sin. 2023; 5: 832-835.

[33] Halsby K, Gildea L, Madhava H. Angulo FJ, Pilz A, Erber W, et al. Clinical manifestations and outcomes of tick-borne encephalitis: a systematic literature review. Ticks Tick Borne Dis. 2024; 15(6): 102407.

[34] Bai Y, Xiao J, Moming A, Fu J, Wang J, Zhou M, et al. Identification and characterization of new Siberian subtype of tick-borne encephalitis virus isolates revealed genetic variations of the Chinese strains. Infect Genet Evol. 2024; 124: 105660.

[35] Ohira M, Yoshii K, Aso Y, Nakajima H, Yamashita T, Takahashi-Iwata I, et al. First evidence of tick-borne encephalitis (TBE) outside of Hokkaido Island in Japan. Emerg Microbes Infect. 2023; 12(2): 2278898.

[36] Kovalev SY, Okulovskaya VY. The first record of Omsk hemorrhagic fever virus and tick-borne encephalitis virus of baltic lineage from the Kemerovo Region of Russia. Vector Borne Zoonotic Dis. 2024; 24(7): 443-450.

[37] Yang D, Li XJ, Tu DZ, Li XL, Wei B. Advances in viral encephalitis: viral transmission, host immunity, and experimental animal models. Zool Res. 2023; 44(3): 525-542.

[38] Peng R, Zhang S, Cui Y, Shi Y, Gao GF, Qi J. Structures of human-infecting Thogotovirus fusogens support a common ancestor with insect baculovirus . Proc Natl Acad Sci U S A. 2017; 114(42): E8905-E8912.

[39] Talactac MR, Yoshii K, Hernandez EP, Kusakisako K, Galay RL, Fujisaki K, et al. Vector competence of Haemaphysalis longicornis ticks for a Japanese isolate of the Thogoto virus . Sci Rep. 2018; 1: 9300.

[40] Lledó L, Giménez-Pardo C, Gegúndez MI. Epidemiological study of Thogoto and Dhori virus infection in people bitten by ticks, and in sheep, in an area of Northern Spain. Int J Environ Res Public Health. 2020; 17(7): 2254.

[41] Xue L, Chang T, Li Z, Wang C, Zhao H, Li M, et al. Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses. Nat Commun. 2024; 15: 4620.

[42] Rupani A, Elshabrawy HA, Bechelli J. Dermatological manifestations of tick-borne viral infections found in the United States. Virol J. 2022; 19(1): 199.

[43] Cleveland DW, Anderson CC, Brissette CA. Borrelia miyamotoi: a comprehensive review . Pathogens. 2023; 12(2): 267.

[44] Du CH, Yang JH, Yao MG, Jiang BG, Zhang Y, He ZH. Systematic investigation of the Borrelia miyamotoi spirochetes in ticks, wildlife and domestic animal hosts in Yunnan province, Southwest China . One Health. 2024; 18: 100735.

[45] Dumler JS, Choi KS, Garcia-Garcia JC, Barat NS, Scorpio DG, Garyu JW. Human granulocytic anaplasmosis and Anaplasma phagocytophilum . Emerg Infect Dis. 2005; 11(12): 1828-1834.

[46] Sullivan MD, Glose K, Sward D. Tick-borne illnesses in emergency and wilderness medicine. Emerg Med Clin North Am. 2024; 42(3): 597-611.

[47] Sharma R, Patil RD, Singh B, Chakraborty S, Chandran D, Dhama K, et al. Tularemia - a re-emerging disease with growing concern. Vet Q. 2023; 1: 1-16.

[48] Waked R, Krause PJ. Human babesiosis. Infect Dis Clin North Am. 2022; 3: 655-670.

[49] Guo WB, Shi WQ, Wang Q, Pan YS, Chang QC, Jiang BG, et al. Distribution of Dermacentor silvarum and associated pathogens: meta-analysis of global published data and a field survey in China . Int J Environ Res Public Health. 2021; 18(9): 4430.

[50] Wang J, Zhang S, Yang J, Liu J, Zhang D, Li Y, et al. Babesia divergens in human in Gansu province, China . Emerg Microbes Infect. 2019; 8(1): 959-961.

[51] Yao J, Liu G, Zou Y, Jiang J, Li S, Wang H, et al. Babesia microti causing intravascular hemolysis in immunocompetent child, China . Emerg Infect Dis. 2023; 29(3): 667-669.

[52] Hong SH, Kim SY, Song BG, Rho JR, Cho CR, Kim CN, et al. Detection and characterization of an emerging type of Babesia sp. similar to Babesia motasi for the first case of human babesiosis and ticks in Korea . Emerg Microbes Infect. 2019; 8(1): 869-878.

[53] Axt CW, Springer A, Strube C, Jung C, Naucke TJ, Müller E, et al. Molecular and serological detection of vector-borne pathogens responsible for equine piroplasmosis in Europe between 2008 and 2021. Microorganisms. 2024; 12(4): 816.

[54] Cloete HPP, Rautenbach Y, Leisewitz AL, Mellanby RJ, Thompson PN, Schoeman JP. Prevalence of co-infections with Ehrlichia spp. or Theileria spp. in dogs naturally infected with babesiosis in the Eastern Cape province . Vet Parasitol Reg Stud Reports. 2024; 54: 101092.

[55] Motavallihaghi S, Fakhar M, Sharbatkhori M, Paghe AS. First molecular evidence of Theileria lestoquardi in small ruminants in northern Iran . Ann Parasitol. 2022; 68(3): 531-536.

[56] Fathi A, Nabavi R, Noaman V, Sarani A, Saadati D, Ben Said M, et al. Molecular identification, risk factor assessment, and phylogenetic analysis of tick-borne pathogens in symptomatic and asymptomatic cattle from South-Eastern Iran. Exp Appl Acarol. 2024; 92(3): 479-506.

[57] Lakew BT, Eastwood S, Walkden-Brown SW. Epidemiology and transmission of Theileria orientalis in Australasia . Pathogens. 2023; 12(10): 1187.

[58] Parfut A, Laugel E, Baer S, Gonzalez G, Hansmann Y, Wendling MJ, et al. Tick-borne encephalitis in pediatrics: an often overlooked diagnosis. Infect Dis Now. 2023; 53(2): 104645.

[59] Yakut N, Kepenekli E, Dogru O. Crimean-Congo hemorrhagic fever with hemophagocytic lymphohistiocytosis. Rev Soc Bras Med Trop. 2021; 54: e0438-2020.

[60] Ergönül Ö. Crimean-Congo haemorrhagic fever. Lancet Infect Dis. 2006; 6(4): 203-214.

[61] Li L, Liu Y, Rao J, Hu H, Liu J, Wang X, et al. Mucin-like protein of Crimean-Congo hemorrhagic fever virus is a key virulence factor and a potent target for developing novel attenuated vaccine. Cell Res. 2025; 35(7): 524-527.

[62] Yang T, Huang H, Jiang L, Li J. Overview of the immunological mechanism underlying severe fever with thrombocytopenia syndrome (Review). Int J Mol Med. 2022; 50(3): 118.

[63] Fill MA, Compton ML, McDonald EC, Moncayo AC, Dunn JR, Schaffner W, et al. Novel clinical and pathologic findings in a heartland virus-associated death. Clin Infect Dis. 2017; 64(4): 510-512.

[64] Savage HM, Godsey MS Jr, Panella NA, Burkhalter KL, Manford J, Trevino-Garrison IC, et al. Surveillance for tick-borne viruses near the location of a fatal human case of bourbon virus (Family Orthomyxoviridae: Genus Thogotovirus) in Eastern Kansas, 2015 . J Med Entomol. 2018; 55(3): 701-705.

[65] Lambert AJ, Velez JO, Brault AC, Calvert AE, Bell-Sakyi L, Bosco-Lauth AM, et al. Molecular, serological and in vitro culture-based characterization of Bourbon virus, a newly described human pathogen of the genus Thogotovirus . J Clin Virol. 2015; 73: 127-132.

[66] Khan M, Beckham JD, Piquet AL, Tyler KL, Pastula DM. An overview of powassan virus disease. Neurohospitalist. 2019; 9(4): 181-182.

[67] Charrel RN, Attoui H, Butenko AM, Clegg JC, Deubel V, Frolova TV, et al. Tick-borne virus diseases of human interest in Europe. Clin Microbiol Infect. 2004; 10(12): 1040-1055.

[68] Růžek D, Yakimenko VV, Karan LS, Tkachev SE. Omsk haemorrhagic fever. Lancet. 2010; 376(9758): 2104-2113.

[69] Zhang Q, Li N, Deng C, Zhang Z, Li X, Yoshii K, et al. Trans complementation of replication-defective Omsk hemorrhagic fever virus for antiviral study. Virol Sin. 2019; 34(4): 412-422.

[70] Owen S, Gaffney C, Grado L, Woodson ML, King JA, Balaraman RP, et al. Colorado tick fever virus induces apoptosis in human endothelial cells to facilitate viral replication. Ticks Tick Borne Dis. 2021; 12(5): 101775.

[71] Shah SZ, Jabbar B, Ahmed N, Rehman A, Nasir H, Nadeem S, et al. Epidemiology, pathogenesis, and control of a tick-borne disease- Kyasanur forest disease: current status and future directions. Front Cell Infect Microbiol. 2018; 8: 149.

[72] Bhatia B, Feldmann H, Marzi A. Kyasanur forest disease and Alkhurma hemorrhagic fever virus-two neglected zoonotic pathogens. Microorganisms. 2020; 8(9): 1406.

[73] Gupta N, Wilson W, Neumayr A, Saravu K. Kyasanur forest disease: a state-of-the-art review. QJM. 2022; 115(6): 351-358.

[74] Chakraborty S, Andrade FCD, Ghosh S, Uelmen J, Ruiz MO. Historical expansion of Kyasanur forest disease in India from 1957 to 2017: a retrospective analysis. Geohealth. 2019; 3(2): 44-55.

[75] Oliveira A, Selvaraj K, Tripathy JP, Betodkar U, Cacodcar J, Quadros N, et al. Geospatial clustering, seasonal trend and forecasting of Kyasanur forest disease in the state of Goa, India, 2015-2018. Trop Med Health. 2020; 48: 27.

[76] Zhang MZ, Bian C, Ye RZ, Cui XM, Chu YL, Yao NN, et al. Human infection with a novel tickborne orthonairovirus species in China. N Engl J Med. 2025; 392(2): 200-202.

[77] Zhang XA, Ma YD, Zhang YF, Hu ZY, Zhang JT, Han S, et al. A new orthonairovirus associated with human febrile illness. N Engl J Med. 2024; 391(9): 821-831.

[78] Jakab Á, Kahlig P, Kuenzli E, Neumayr A. Tick borne relapsing fever - a systematic review and analysis of the literature. PLoS Negl Trop Dis. 2022; 16(2): e0010212.

[79] Krause PJ, Fish D, Narasimhan S, Barbour AG. Borrelia miyamotoi infection in nature and in humans . Clin Microbiol Infect. 2015; 7: 631-639.

[80] Jiang BG, Jia N, Jiang JF, Zheng YC, Chu YL, Jiang RR, et al. Borrelia miyamotoi infections in humans and ticks, Northeastern China . Emerg Infect Dis. 2018; 24(2): 236-241.

[81] Boulanger N, Boyer P, Talagrand-Reboul E, Hansmann Y. Ticks and tick-borne diseases. Med Mal Infect. 2019; 49(2): 87-97.

[82] Eldin C, Mélenotte C, Mediannikov O, Ghigo E, Million M, Edouard S, et al. From Q fever to Coxiella burnetii infection: a paradigm change . Clin Microbiol Rev. 2017; 30(1): 115-190.

[83] Körner S, Makert GR, Ulbert S, Pfeffer M, Mertens-Scholz K. The prevalence of coxiella burnetii in hard ticks in Europe and their role in Q Fever transmission revisited-a systematic review . Front Vet Sci. 2021; 8: 655715. doi: 10.3389/fvets.2021.655715.

[84] Spernovasilis N, Markaki I, Papadakis M, Mazonakis N, Ierodiakonou D. Mediterranean spotted fever: current knowledge and recent advances. Trop Med Infect Dis. 2021; 6(4): 172.

[85] Moore A, Nelson C, Molins C, Mead P, Schriefer M. Current guidelines, common clinical pitfalls, and future directions for laboratory diagnosis of Lyme disease, United States. Emerg Infect Dis. 2016; 22(7): 1169-1177.

[86] Nadelman RB, Hanincová K, Mukherjee P, Liveris D, Nowakowski J, McKenna D, et al. Differentiation of reinfection from relapse in recurrent Lyme disease. N Engl J Med. 2012; 367(20): 1883-1890.

[87] Madison-Antenucci S, Kramer LD, Gebhardt LL, Kauffman E . Emerging tick-borne diseases. Clin Microbiol Rev. 2020; 33(2): 10-1128.

[88] Portillo A, Santibáñez P, Palomar AM, Santibáñez S, Oteo JA. ‘ Candidatus Neoehrlichia mikurensis’ in Europe . New Microbes New Infect. 2018; 22: 30-36.

[89] Chaorattanakawee S, Tachavarong W, Hananantachai H, Bunsermyos W, Chanarat N, Promsathaporn S, et al. Seasonal pattern of questing ticks and prevalence of pathogenic Rickettsia and Anaplasmataceae in Khao Yai national park, Thailand . Travel Med Infect Dis. 2024; 58: 102696.

[90] Steiner DJ, Furuya Y, Metzger DW. Host-pathogen interactions and immune evasion strategies in Francisella tularensis pathogenicity . Infect Drug Resist. 2014; 7: 239-251.

[91] Chen M, Liu Q, Xue J, Chen S, Huang D, Yu Y, et al. Spreading of human babesiosis in China: current epidemiological status and future challenges. China CDC Wkly. 2020; 2(33): 634-637.

[92] Abdelbaset AE, Nonaka N, Nakao R . Tick-borne diseases in Egypt: a one health perspective. One Health. 2022; 15: 100443.

[93] Al-Hosary A, Ahmed L, Ahmed J, Nijhof A, Clausen PH. Epidemiological study on tropical theileriosis (Theileria annulata infection) in the Egyptian Oases with special reference to the molecular characterization of Theileria spp. Ticks Tick Borne Dis. 2018; 9(6): 1489-1493.

[94] Baneth G. Perspectives on canine and feline hepatozoonosis. Vet Parasitol. 2011; 181(1): 3-11.

[95] Baneth G, Allen K. Hepatozoonosis of dogs and cats. Vet Clin North Am Small Anim Pract. 2022; 52(6): 1341-1358.

[96] Greay TL, Gofton AW, Paparini A, Ryan UM, Oskam CL, Irwin PJ. Recent insights into the tick microbiome gained through next-generation sequencing. Parasit Vectors. 2018; 11: 12.

[97] Tian D, Ye RZ, Li YY, Wang N, Gao WY, Wang BH, et al. Virome specific to tick genus with distinct ecogeographical distribution. Microbiome. 2025; 13(1): 57.

[98] Song X, Zhong Z, Gao L, Weiss BL, Wang J. Metabolic interactions between disease-transmitting vectors and their microbiota. Trends Parasitol. 2022; 38(8): 697-708.

[99] Zhong Z, Zhong T, Peng Y, Zhou X, Wang Z, Tang H, et al. Symbiont-regulated serotonin biosynthesis modulates tick feeding activity. Cell Host Microbe. 2021; 29(10): 1545-1557.e1544.

[100] Smith TA, Driscoll T, Gillespie JJ, Raghavan R. A Coxiella-like endosymbiont is a potential vitamin source for the Lone Star tick . Genome Biol Evol. 2015; 7(3): 831-838.

[101] Guizzo MG, Parizi LF, Nunes RD, Schama R, Albano RM, Tirloni L, et al. A Coxiella mutualist symbiont is essential to the development of Rhipicephalus microplus . Sci Rep. 2017; 7(1): 17554.

[102] Machado-Ferreira E, Vizzoni VF, Balsemão-Pires E, Moerbeck L, Gazeta GS, Piesman J, et al. Coxiella symbionts are widespread into hard ticks . Parasitol Res. 2016; 115(12): 4691-4699.

[103] Liu JN, Yu ZJ, Liu LM, Li NX, Wang RR, Zhang CM, et al. Identification, distribution and population dynamics of Francisella-like endosymbiont in Haemaphysalis doenitzi (Acari: Ixodidae) . Sci Rep. 2016; 6: 35178.

[104] Gerhart JG, Auguste Dutcher H, Brenner AE, Moses AS, Grubhoffer L, Raghavan R. Multiple acquisitions of pathogen-derived Francisella endosymbionts in soft ticks . Genome Biol Evol. 2018; 10(2): 607-615.

[105] Sassera D, Lo N, Epis S, D’Auria G, Montagna M, Comandatore F, et al. Phylogenomic evidence for the presence of a flagellum and cbb(3) oxidase in the free-living mitochondrial ancestor. Mol Biol Evol. 2011; 28(12): 3285-3296.

[106] Mukhacheva TA, Kovalev SY. Bacteria of the family ‘ Candidatus Midichloriaceae’ in sympatric zones of Ixodes ticks: genetic evidence for vertical transmission . Microb Ecol. 2017; 74(1): 185-193.

[107] Lejal E, Chiquet J, Aubert J, Robin S, Estrada-Peña A, Rue O, et al. Temporal patterns in Ixodes ricinus microbial communities: an insight into tick-borne microbe interactions . Microbiome. 2021; 9: 153.

[108] Binetruy F, Bailly X, Chevillon C, Martin OY, Bernasconi MV, Duron O. Phylogenetics of the Spiroplasma ixodetis endosymbiont reveals past transfers between ticks and other arthropods . Ticks Tick Borne Dis. 2019; 10(3): 575-584.

[109] Sazama EJ, Ouellette SP, Wesner JS. Bacterial endosymbionts are common among, but not necessarily within, insect species. Environ Entomol. 2019; 48(1): 127-133.

[110] Cull B, Burkhardt NY, Wang XR, Thorpe CJ, Oliver JD, Kurtti TJ, et al. The Ixodes scapularis symbiont Rickettsia buchneri inhibits growth of pathogenic rickettsiaceae in tick cells: implications for vector competence . Front Vet Sci. 2021; 8: 748427.

[111] Bonnet SI, Binetruy F, Hernández-Jarguín AM, Duron O. The tick microbiome: why non-pathogenic microorganisms matter in tick biology and pathogen transmission. Front Cell Infect Microbiol. 2017; 7: 236.

[112] Chen HY, Li CQ, Chen SY, Xiao H. Metagenomic analysis reveals hidden links between gut microbes and habitat adaptation among cave and surface dwelling Sinocyclocheilus species . Zool Res. 2023; 44(4): 793-807.

[113] Wang HY, Liu LX, Chen XY, Zhang YD, Li WX, Li WW. Comprehensive analysis of the gut microbiome and post-translational modifications elucidates the route involved in microbiota-host interactions. Zool Res. 2024; 45(1): 95-107.

[114] Maitre A, Kratou M, Corona-Guerrero I, Abuin-Denis L, Mateos-Hernández L, Mosqueda J, et al. Differential interactions of Rickettsia species with tick microbiota in Rh. sanguineus and Rh. turanicus . Sci Rep. 2024; 14(1): 20674.

[115] Kolo AO, Raghavan R. Impact of endosymbionts on tick physiology and fitness. Parasitology. 2023; 150(10): 859-865.

[116] Cibichakravarthy B, Oses-Prieto JA, Ben-Yosef M, Burlingame AL, Karr TL, Gottlieb Y. Comparative proteomics of Coxiella like endosymbionts (CLEs) in the symbiotic organs of Rhipicephalus sanguineus ticks . Microbiol Spectr. 2022; 10(1): e0167321.

[117] Olivieri E, Epis S, Castelli M, Varotto Boccazzi I, Romeo C, Desirò A, et al. Tissue tropism and metabolic pathways of Midichloria mitochondrii suggest tissue-specific functions in the symbiosis with Ixodes ricinus . Ticks Tick Borne Dis. 2019; 10(5): 1070-1077.

[118] Brinkerhoff RJ, Clark C, Ocasio K, Gauthier DT, Hynes WL. Factors affecting the microbiome of Ixodes scapularis and Amblyomma americanum . PLoS One. 2020; 15(5): e0232398.

[119] Zhang R, Yu G, Huang Z, Zhang Z. Microbiota assessment across different developmental stages of Dermacentor silvarum (Acari: Ixodidae) revealed stage-specific signatures . Ticks Tick Borne Dis. 2020; 11(2): 101321.

[120] Pollet T, Sprong H, Lejal E, Krawczyk AI, Moutailler S, Cosson JF, et al. The scale affects our view on the identification and distribution of microbial communities in ticks. Parasit Vectors. 2020; 13(1): 36.

[121] Ahantarig A, Trinachartvanit W, Baimai V, Grubhoffer L. Hard ticks and their bacterial endosymbionts (or would be pathogens). Folia Microbiol (Praha). 2013; 58(5): 419-428.

[122] Bonnet SI, Pollet T. Update on the intricate tango between tick microbiomes and tick-borne pathogens. Parasite Immunol. 2021; 43(5): e12813.

[123] Narasimhan S, Rajeevan N, Liu L, Zhao YO, Heisig J, Pan J, et al. Gut microbiota of the tick vector Ixodes scapularis modulate colonization of the Lyme disease spirochete . Cell Host Microbe. 2014; 15(1): 58-71.

[124] Kitsou C, Foor SD, Dutta S, Bista S, Pal U. Tick gut barriers impacting tick-microbe interactions and pathogen persistence. Mol Microbiol. 2021; 116(5): 1241-1248.

[125] Yang X, Koči J, Smith AA, Zhuang X, Sharma K, Dutta S, et al. A novel tick protein supports integrity of gut peritrophic matrix impacting existence of gut microbiome and Lyme disease pathogens. Cell Microbiol. 2021; 23(2): e13275.

[126] Narasimhan S, Fikrig E. Tick microbiome: the force within. Trends Parasitol. 2015; 31(7): 315-323.

[127] Maqbool M, Sajid MS, Saqib M, Anjum FR, Tayyab MH, Rizwan HM, et al. Potential mechanisms of transmission of tick-borne viruses at the virus-tick interface. Front Microbiol. 2022; 13: 846884.

[128] Talactac MR, Hernandez EP, Hatta T, Yoshii K, Kusakisako K, Tsuji N, et al. The antiviral immunity of ticks against transmitted viral pathogens. Dev Comp Immunol. 2021; 119: 104012.

[129] Sonenshine DE, Macaluso KR. Microbial invasion vs. tick immune regulation. Front Cell Infect Microbiol. 2017; 7: 390.

[130] Fogaça AC, Sousa G, Pavanelo DB, Esteves E, Martins LA, Urbanová V, et al. Tick immune system: what is known, the interconnections, the gaps, and the challenges. Front Immunol. 2021; 12: 628054.

[131] Rosa RD, Capelli-Peixoto J, Mesquita RD, Kalil SP, Pohl PC, Braz GR, et al. Exploring the immune signalling pathway-related genes of the cattle tick Rhipicephalus microplus: from molecular characterization to transcriptional profile upon microbial challenge . Dev Comp Immunol. 2016; 59: 1-14.

[132] O’Neal AJ, Singh N, Rolandelli A, Laukaitis HJ, Wang X, Shaw DK, et al. Croquemort elicits activation of the immune deficiency pathway in ticks. Proc Natl Acad Sci U S A. 2023; 120(20): e2208673120.

[133] Sidak-Loftis LC, Rosche KL, Pence N, Ujczo JK, Hurtado J, Fisk EA, et al. The unfolded-protein response triggers the arthropod immune deficiency pathway. mBio. 2022; 13(4): e0070322.

[134] Harrison DA, McCoon PE, Binari R, Gilman M, Perrimon N . Drosophila unpaired encodes a secreted protein that activates the JAK signaling pathway . Genes Dev. 1998; 12(20): 3252-3263.

[135] Rana VS, Kitsou C, Dutta S, Ronzetti MH, Zhang M, Bernard Q, et al. Dome1-JAK-STAT signaling between parasite and host integrates vector immunity and development. Science. 2023; 379(6628): eabl3837.

[136] Liu L, Dai J, Zhao YO, Narasimhan S, Yang Y, Zhang L, et al. Ixodes scapularis JAK-STAT pathway regulates tick antimicrobial peptides, thereby controlling the agent of human granulocytic anaplasmosis . J Infect Dis. 2012; 206(8): 1233-1241.

[137] Khogali R, Bastos A, Getange D, Kalayou S, Ongeso N, Petra Verhoeven JT, et al. Exploring the microbiomes of camel ticks to infer vector competence: insights from tissue-level symbiont-pathogen relationships. Sci Rep. 2025; 15: 5574.

[138] Gall CA, Reif KE, Scoles GA, Mason KL, Mousel M, Noh SM, et al. The bacterial microbiome of Dermacentor andersoni ticks influences pathogen susceptibility . ISME J. 2016; 10(8): 1846-1855.

[139] Skinner KM, Underwood J, Ghosh A, Oliva Chavez AS, Brelsfoard CL. Wolbachia impacts Anaplasma infection in Ixodes scapularis tick cells . Int J Environ Res Public Health. 2022; 19(3): 1051.

[140] Duron O, Morel O, Noël V, Buysse M, Binetruy F, Lancelot R, et al. Tick-bacteria mutualism depends on B vitamin synthesis pathways. Curr Biol. 2018; 28(12): 1896-1902.e1895.

[141] Abraham NM, Liu L, Jutras BL, Yadav AK, Narasimhan S, Gopalakrishnan V, et al. Pathogen-mediated manipulation of arthropod microbiota to promote infection. Proc Natl Acad Sci U S A. 2017; 114(5): E781-E790.

[142] Kurokawa C, Lynn GE, Pedra JHF, Pal U, Narasimhan S, Fikrig E. Interactions between Borrelia burgdorferi and ticks . Nat Rev Microbiol. 2020; 18(10): 587-600.

[143] Narasimhan S, Rajeevan N, Graham M, Wu MJ, DePonte K, Marion S, et al. Tick transmission of Borrelia burgdorferi to the murine host is not influenced by environmentally acquired midgut microbiota . Microbiome. 2022; 10: 173.

[144] Hamilton PT, Maluenda E, Sarr A, Belli A, Hurry G, Duron O, et al. Borrelia afzelii infection in the rodent host has dramatic effects on the bacterial microbiome of Ixodes ricinus ticks . Appl Environ Microbiol. 2021; 87(18): e0064121.

[145] Mota TF, Fukutani ER, Martins KA, Salgado VR, Andrade BB, Fraga DBM, et al. Another tick bites the dust: exploring the association of microbial composition with a broad transmission competence of tick vector species. Microbiol Spectr. 2023; 11(6): e0215623.

[146] Zhang L, Wang D, Shi P, Li J, Niu J, Chen J, et al. A naturally isolated symbiotic bacterium suppresses flavivirus transmission by Aedes mosquitoes . Science. 2024; 384(6693): eadn9524.

[147] Hu W, Gao H, Cui C, Wang L, Wang Y, Li Y, et al. Harnessing engineered symbionts to combat concurrent malaria and arboviruses transmission. Nat Commun. 2025; 16(1): 2104.

[148] Mateos-Hernández L, Obregón D, Maye J, Borneres J, Versille N, de la Fuente J, et al. Anti-tick microbiota vaccine impacts Ixodes ricinus performance during feeding . Vaccines (Basel). 2020; 8(4): 702.

[149] Maitre A, Mateos-Hernandez L, Kratou M, Egri N, Maye J, Juan M, et al. Effects of live and peptide-based antimicrobiota vaccines on Ixodes ricinus fitness, microbiota, and acquisition of tick-borne pathogens . Pathogens. 2025; 14(3): 206.

[150] Leclerc L, Mattick J, Burns BP, Sassera D, Hotopp JD, Lo N. Metatranscriptomics provide insights into the role of the symbiont Midichloria mitochondrii in Ixodes ticks . FEMS Microbiol Ecol. 2024; 100(12): fiae133.

[151] Abbas MN, Jmel MA, Mekki I, Dijkgraaf I, Kotsyfakis M. Recent advances in tick antigen discovery and anti-tick vaccine development. Int J Mol Sci. 2023; 24(5): 4969.

[152] de la Fuente J, Mazuecos L, Contreras M. Innovative approaches for the control of ticks and tick-borne diseases. Ticks Tick Borne Dis. 2023; 14(6): 102227.

[153] Maldonado-Ruiz LP, Park Y, Zurek L. Liquid water intake of the lone star tick, Amblyomma americanum: implications for tick survival and management . Sci Rep. 2020; 10(1): 6000.

[154] Li LH, Zhang Y, Zhu D. Effects of antibiotic treatment on the fecundity of Rhipicephalus haemaphysaloides ticks . Parasit Vectors. 2018; 11: 242.

[155] Zhang L, Han J, Zhou Q, He Z, Sun SW, Li R, et al. Differential microbial composition in parasitic vs. questing ticks based on 16S next-generation sequencing. Front Microbiol. 2023; 14: 1264939.

[156] Daifalla N, Cayabyab MJ, Xie E, Kim HB, Tzipori S, Stashenko P, et al. Commensal Streptococcus mitis is a unique vector for oral mucosal vaccination . Microbes Infect. 2015; 17(3): 237-242.

[157] Chen X, Shi T, Chen F, Xie X, Fang H, Wu Z. Orally antigen-engineered yeast vaccine elicits robust intestinal mucosal immunity. ACS Nano. 2025; 19(11): 10841-10853.

[158] Antunes S, Domingos A. Tick vaccines and concealed versus exposed antigens. Pathogens. 2023; 12(3): 374.

[159] Bai X, Huang Z, Duraj-Thatte AM, Ebert MP, Zhang F, Burgermeister E, et al. Engineering the gut microbiome. Nat Rev Bioeng. 2023; 1: 665-679.

[160] Jin L, Jiang BG, Yin Y, Guo J, Jiang JF, Qi X, et al. Interference with LTβR signaling by tick saliva facilitates transmission of Lyme disease spirochetes. Proc Natl Acad Sci U S A. 2022; 119(47): e2208274119.

[161] Rodríguez-Mallon A. The Bm86 discovery: a revolution in the development of anti-tick vaccines. Pathogens. 2023; 12(2): 231.