Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI44310.15789/2220-7619-2016-4-315-324REVIEWSОБЗОРЫUnknown«CANDIDATUS MIDICHLORIA MITOCHONDRII»: A NEW MEMBER OF ORDER RICKETTSIALES, ENDOSYMBIONT OF IXODES RICINUS TICK«CANDIDATUS MIDICHLORIA MITOCHONDRII» — НОВЫЙ ПРЕДСТАВИТЕЛЬ ПОРЯДКА RICKETTSIALES, ЭНДОСИМБИОНТ КЛЕЩЕЙ IXODES RICINUSShpynovS. N.ШпыновС. Н.
Russian Federation

PhD, MD (Medicine), Head of Laboratory of Ecology of Rickettsiae

д.м.н., руководитель лаборатории экологии риккетсий 

stan63@inbox.ruN.F. Gamaleya Federal Center of Epidemiology and Microbiology, Moscow, Russian FederationФГБУ Федеральный научно-исследовательский центр эпидемиологии и микробиологии им. Н.Ф. Гамалеи МЗ РФ, Москва, Россия06122016643153240501201705012017Copyright ©; 2016, Shpynov S.N.Copyright ©; 2016, Шпынов С.Н.2016Shpynov S.N.Шпынов С.Н.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/443

«Candidatus Midichloria mitochondrii» is the sheep tick Ixodes ricinus endosymbiont. This unique bacteria can occupy and persist within the mitochondria of animals. I. ricinus is an important vector of human pathogens in natural focal of infections. «Candidatus M. mitochondrii» found in the intermembrane space of mitochondria and in the cytoplasm of ovarian cells in 100% females of I. ricinus. The bacteria contain flagella in the salivary glands of ticks. «Candidatus M. mitochondrii» has two groups of unique genes for the members of the order Rickettsiales (cbb3 cytochrome oxidase and flagellin), which allows it to play an important role in embryogenesis of the I. ricinus ticks and cause seroconversion in 58% of patients after ticks bloodsucking. This bacterium formed MALOs group (midichloria and like organisms) with genetically closely related organisms which demonstrated a association with a wide range of host from arthropods to ciliates, amoebae, sponges, fish and various animals and humans. Now there is no data about replication the «Candidatus M. mitochondrii» in humans and pathogenicity of this microorganism. Although a high percentage of seropositive samples obtained from patients after bloodsucking of I. ricinus in anamnesis, this bacterium cannot yet be regarded as responsible for the pathology as known human pathogenic from order Rickettsi-ales (Rickettsia, Anaplasma and Ehrlichia spp.). Needed to reconsider the attitude to an immune response to the saliva of I. ricinus, taking into account the potential impact of «Candidatus M. mitochondrii». It is considered highly possible role of this bacterium in the immune response and immunomodulation in humans with bloodsucking of I. ricinus in anamnesis. DNA of «Candidatus M. mitochondrii» was the first time detected in I. ricinus ticks from European part of Russia.

Эндосимбионт иксодовых клещей Ixodes ricinus «Candidatus Midichloria mitochondrii» единственная из известных бактерий, которая может вторгаться и существовать внутри митохондрий животных. Ее хозяин — иксодовый клещ I. ricinus, является переносчиком возбудителей важных природно-очаговых заболеваний человека. «Candidatus M. mitochondrii» обнаружена в межмембранном пространстве митохондрий и в цитоплазме овариальных клеток у 100% самок I. ricinus. При локализации в слюнных железах клещей бактерия содержит жгутик. «Candidatus M. mitochondrii» имеет две группы генов (cbb3 цитохром оксидазу и флагеллин) уникальных для представителей порядка Rickettsiales, что позволяет ей играть важную роль в эмбриогенезе клещей I. ricinus и вызывать сероконверсию у 58% пациентов с присасыванием этого вида клещей в анамнезе. Недавно в порядке Rickettsiales было предложено выделить семейство «Candidatus Midichloriaceae» и внутри него род «Candidatus Midichloria», получившие названия в честь «Candidatus M. mitochondrii». Эта бактерия вместе с генетически близкородственными микроорганизмами образовала группу MALOs (midichloria and like organisms), представители которой продемонстрировали связь с широким кругом хозяев: от членистоногих до инфузорий, амеб, губок, рыб, различных животных и человека. В настоящее время отсутствуют данные о возможности репликации «Candidatus M. mitochondrii» в организме человека и патогенности этого микроорганизма. Несмотря на высокий процент серопозитивных проб, полученных от лиц с присасыванием I. ricinus в анамнезе, эту бактерию пока нельзя рассматривать как ответственную за патологию человека по примеру известных патогенных представителей порядка Rickettsiales (риккетсии, анаплазмы и эрлихии). Требуется пересмотреть отношение к иммунному ответу к слюне I. ricinus с учетом потенциального воздействия «Candidatus M. mitochondrii». Следует рассматривать высокую возможность роли этой бактерии в иммунном ответе и иммуномодуляции у человека с присасыванием I. ricinus в анамнезе. ДНК «Candidatus M. mitochondrii» была впервые генотипирована в клещах I. ricinus на территории Европейской части Российской Федерации.

«Candidatus Midichloria mitochondrii»endosymbiontMALOs (midichloria and like organisms)order RickettsialesticksIxodes ricinusmitochondria«Candidatus Midichloria mitochondrii»эндосимбионтгруппа MALOs (midichloria and like organisms)порядок Rickettsialesиксодовые клещиIxodes ricinusмитохондрия1.Медянников О.Ю., Иванов Л.И., Nishikawa M., Saito R., Сидельников И.Н., Здановская Н.И., Мокрецова Е.В., Тарасевич И.В., Suzuki H. Микроорганизм «Montezuma» из порядка Rickettsiales: потенциальный возбудитель клещевого трансмиссивного заболевания на Дальнем Востоке России // Журнал микробиологии, эпидемиологии и иммунобиологии. 2004. № 1. С. 7–13. [Mediannikov O., Ivanov L.I., Nishikawa M., Saito R., Sidel’nikov I.N., Zdanovskaia N.I., Mokretsova E.V., Tarasevich I.V., Suzuki H. Microorganism “Montezuma” of the order Rickettsiales: the potential causative agent of tick-borne disease in the Far East of Russia. Zhurnal mikrobiologii, epidemiologii i immunobiologii = Journal of Microbiology, Epidemiology and Immunobiology, 2004, no. l, pp. 7–13. (In Russ.)]2.Филиппова Н.А. Иксодовые клещи подсемейства Ixodinae. Л.: Наука, 1977. 396 с. [Filippova N.A. Iksodovye kleshhi podsemejstva Ixodinae [Ixodidae, Ticks of Subfamily of Ixodinae]. Leningrad: Nauka, 1977. 396 p.]3.Bazzocchi C., Mariconti M., Sassera D., Rinaldi L., Martin E., Cringoli G., Urbanelli S., Genchi C., Bandi C., Epis S. Molecular and serological evidence for the circulation of the tick symbiont Midichloria (Rickettsiales: Midichloriaceae) in different mammalian species. Parasites & Vectors, 2013, no. 6, pp. 350–356. doi: 10.1186/1756-3305-6-3504.Beninati T., Lo N., Sacchi L., Genchi C., Noda H., Bandi C. A novel alpha-Proteobacterium resides in the mitochondria of ovarian cells of the tick Ixodes ricinus. Appl. Environ. Microbiol., 2004, no. 70, pp. 2596–2602. doi: 10.1128/AEM.70.5.2596-2602.20045.Beninati T., Riegler M., Vilcins I.M., Sacchi L., McFadyen R., Krockenberger M., Bandi C., O’Neill S.L., Lo N. Absence of the symbiont Candidatus Midichloria mitochondrii in the mitochondria of the tick Ixodes holocyclus. FEMS Microbiol. Lett., 2009, no. 299, pp. 241–247. doi: 10.1186/s13071-015-0958-36.Boscaro V., Petroni G., Ristori A., Verni F., Vannini C. “Candidatus Defluviella procrastinata” and “Candidatus Cytrobacter zanobii”, two novel ciliate endosymbionts belonging to the “Midichloria clade”. Microb. Ecol., 2013, no. 65, pp. 302–310. doi: 10.1007/s00248-012-0170-37.Dumler J., Walker D. Order II. Rickettsiales Gieszczykiewicz 1939, 25AL emend. In: Bergey’s manual of systematic bacteriology. 2nd ed. Ed. Garrity G., Brenner D., Krieg N., Staley J. New York, Springer-Verlag, 2005, pp. 96–160.8.Epis S., Mandrioli M., Genchi M., Montagna M., Sacchi L., Pistone D., Sassera D. Localization of the bacterial symbiont Candidatus Midichloria mitochondrii within the hard tick Ixodes ricinus by whole-mount FISH staining. Ticks Tick-Borne Dis., 2013, no. 4, pp. 39–45. doi: 10.1016/j.ttbdis.2012.06.0059.Epis S., Sassera D., Beninati T., Lo N., Beati L., Piesman J., Rinaldi L., McCoy K.D., Torina A., Sacchi L., Clementi E., Genchi M., Magnino S., Bandi C. Midichloria mitochondrii is widespread in hard ticks (Ixodidae) and resides in the mitochondria of phylogenetically diverse species. Parasitology, 2008, no. 135, pp. 485–494. doi: 10.1017/S003118200700405210.Fraune S., Bosch T.C. Long-term maintenance of species-specific bacterial microbiota in the basal metazoan Hydra. Proc. Natl. Acad. Sci. USA, 2007, no. 104, pp. 13146–13151. doi: 10.1073/pnas.070337510411.Gofton A.W., Oskam C.L., Lo N., Beninati T., Wei H., McCarl V., Murray D.C., Paparini A., Greay T.L., Holmes A.J., Bunce M., Ryan U., Irwin P. Inhibition of the endosymbiont “Candidatus Midichloria mitochondrii” during 16S rRNA gene profiling reveals potential pathogens in Ixodes ticks from Australia. Parasit Vectors, 2015, no. 25, pp. 345–352. doi: 10.1186/s13071-015-0958-312.Granquist E.G., Kristiansson M., Lindgren P.E., Matussek A., Nødtvedt A., Okstad W., Stuen S. Evaluation of microbial communities and symbionts in Ixodes ricinus and ungulate hosts (Cervus elaphus and Ovis aries) from shared habitats on the west coast of Norway. Ticks Tick Borne Dis., 2014, no. 5 (6), pp. 780–784. doi: 10.1016/j.ttbdis.2014.05.00513.Harrus S., Perlman-Avrahami A., Mumcuoglu K.Y., Morick D., Eyal O., Baneth G. Molecular detection of Ehrlichia canis, Anaplasma bovis, Anaplasma platys, Candidatus Midichloria mitochondrii and Babesia canis vogeli in ticks from Israel. Clin. Microbiol. Infect., 2011, no. 17 (3), pp. 459–463. doi: 10.1111/j.1469-0691.2010.03316.x14.Hess S., Suthaus A., Melkonian M. “Candidatus Finniella” (Rickettsiales, Alphaproteobacteria), Novel Endosymbionts of Viridiraptorid Amoeboflagellates (Cercozoa, Rhizaria). Appl. Environ. Microbiol., 2015, vol. 82, no. 2, pp. 659–670. doi: 10.1128/AEM.02680-1515.Jiang J., Maina A.N., Knobel D.L., Cleaveland S., Laudisoit A., Wamburu K., Ogola E., Parola P., Breiman R.F., Njenga M.K., Richards A.L. Molecular detection of Rickettsia felis and Candidatus Rickettsia asemboensis in fleas from human habitats, Asembo, Kenya. Vector Borne Zoonotic Dis., 2013, no. 13 (8), pp. 550–558. doi:10.1089/vbz.2012.112316.Lewis D. The detection of rickettsia-like microorganisms within the ovaries of female Ixodes ricinus ticks. Z. Parasitenkd., 1979, no. 59 (3), pp. 295–298.17.Lloyd S.J., LaPatra S.E., Snekvik K.R., St-Hilaire S., Cain K.D., Call D.R. Strawberry disease lesions in rainbow trout from southern Idaho are associated with DNA from a Rickettsia-like organism. Dis. Aquat. Organ., 2008, no. 82, pp. 111–118. doi: 10.3354/dao0196918.Lommano E., Bertaiola L., Dupasquier C., Gern L. Infections and coinfections of questing Ixodes ricinus ticks by emerging zoo notic pathogens in Western Switzerland. Appl. Environ. Microbiol., 2012, no. 78 (13), pp. 4606–4612. doi: 10.1128/AEM.07961-1119.Mariconti M., Epis S., Gaibani P., Dalla Valle C., Sassera D., Tomao P., Fabbi M., Castelli F., Marone P., Sambri V., Bazzocchi C., Bandi C. Humans parasitized by the hard tick Ixodes ricinus are seropositive to Midichloria mitochondrii: is Midichloria a novel pathogen, or just a marker of tick bite? Pathog. Glob. Health, 2012, vol. 106, no. 7, pp. 391–396. doi: 10.1179/2047773212Y.000000005020.Mariconti M., Epis S., Sacchi L., Biggiogera M., Sassera D., Genchi M., Alberti E., Montagna M., Bandi C., Bazzocchi C. A study on the presence of flagella in the order Rickettsiales: the case of “Candidatus Midichloria mitochondrii. Microbiology, 2012, vol. 158, iss. 7 , pp. 1677–1683. doi: 10.1099/mic.0.057174-021.Matsuura Y., Kikuchi Y., Meng X.Y., Koga R., Fukatsu T. Novel clade of alphaproteobacterial endosymbionts associated with stinkbugs and other arthropods. Appl. Environ. Microbiol., 2012, no. 78, pp. 4149–4156. doi: 10.1128/AEM.00673-1222.Mediannikov O., Aubadie-Ladrix M., Raoult D. Candidatus “Rickettsia senegalensis” in cat fleas in Senegal. New Microbes New Infect., 2015, no. 3, pp. 24–28. doi: 10.1016/j.nmni.2014.10.00523.Montagna M., Sassera D., Epis S., Bazzocchi C., Vannini C., Lo N., Sacchi L., Fukatsu T., Petroni G., Bandi C. “Candidatus Midichloriaceae” fam. nov. (Rickettsiales), an ecologically widespread clade of intracellular Alphaproteobacteria. Appl. Environ. Microbiol., 2013, no. 79, pp. 3241–3248. doi: 10.1128/AEM.03971-1224.Murray R.G., Stackebrandt E. Taxonomic note: implementation of the provisional status Candidatus for incompletely described procaryotes. Int. J. Syst. Bacteriol., 1995, no. 45 (1), pp. 186–187.25.Ninio C., Plantard O., Serra V., Pollera C., Ferrari N., Cafiso A., Sassera D., Bazzocchi C. Antibiotic treatment of the hard tick Ixodes ricinus: influence on Midichloria mitochondrii load following blood meal. Ticks Tick Borne Dis., 2015, no. 6 (5), pp. 653– 657. doi: 10.1016/j.ttbdis.2015.05.01126.Palomar A.M., Portillo A., Santibáñez P., Mazuelas D., Roncero L., García-Álvarez L., Santibáñez S., Gutiérrez Ó., Oteo J.A. Detection of tick-borne Anaplasma bovis, Anaplasma phagocytophilum and Anaplasma centrale in Spain. Med. Vet. Entomol., 2015, no. 29(3), pp. 349–353. doi: 10.1111/mve.1212427.Parola P., Paddock C.D., Socolovschi C., Labruna M.B., Mediannikov O., Kernif T., Abdad M.Y., Stenos J., Bitam I., Fournier P.E., Raoult D. Update on tick-borne rickettsioses around the world: a geographic approach. Clin. Microbiol. Rev., 2013, no. 26 (4), pp. 657–702. doi: 10.1128/CMR.00032-1328.Paulsen K.M., Pedersen B.N., Soleng A., Okbaldet Y.B., Pettersson J.H., Dudman S.G., Ottesen P., Vik I.S., Vainio K., Andreassen Å. Prevalence of tick-borne encephalitis virus in Ixodes ricinus ticks from three islands in north-western Norway. APMIS, 2015, no. 123 (9), pp. 759–764. doi: 10.1111/apm.1241229.Ponnusamy L., Gonzalez A., Van Treuren W., Weiss S., Parobek C.M., Juliano J.J., Knight R., Roe R.M., Apperson C.S., Meshnick S.R. Diversity of Rickettsiales in the microbiome of the lone star tick, Amblyomma americanum. Appl. Environ. Microbiol., 2014, no. 80 (1), pp. 354–359. doi: 10.1128/AEM.02987-1330.Rendulic S., Jagtap P., Rosinus A., Eppinger M., Baar C., Lanz C., Keller H., Lambert C., Evans K.J., Goesmann A., Meyer F., Sockett R.E., Schuster S.C. A predator unmasked: life cycle of Bdellovibrio bacteriovorus from a genomic perspective. Science, 2004, vol. 303, iss. 5658, pp. 689–692. doi: 10.1126/science.109302731.Reye A.L., Stegniy V., Mishaeva N.P., Velhin S., Hübschen J.M., Ignatyev G., Muller C.P. Prevalence of tick-borne pathogens in Ixodes ricinus and Dermacentor reticulatus ticks from different geographical locations in Belarus. PLoS One, 2013, no. 8 (1): e54476. doi: 10.1371/journal.pone.0054476.32.Rizzoli A., Silaghi C., Obiegala A., Rudolf I., Hubálek Z., Földvári G., Plantard O., Vayssier-Taussat M., Bonnet S., Spitalská E., Kazimírová M. Ixodes ricinus and its transmitted pathogens in urban and peri-urban areas in Europe: new hazards and relevance for public health. Front. Public. Health., 2014, vol. 2:251. doi: 10.3389/fpubh.2014.0025133.Roux V., Rydkina E., Eremeeva M., Raoult D. Citrate synthase gene comparison, a new tool for phylogenetic analysis, and its application for the rickettsiae. Int. J. Syst. Bacteriol., 1997, no. 47 (2), pp. 252–261. doi: 10.1099/00207713-47-2-25234.Sacchi L., Bigliardi E., Corona S., Beninati T., Lo N., Franceschi A. A symbiont of the tick Ixodes ricinus invades and consumes mitochondria in a mode similar to that of the parasitic bacterium Bdellovibrio bacteriovorus. Tissue Cell, 2004, no. 36, pp. 43–53. doi: 10.1016/j.tice.2003.08.00435.Sanogo Y.O., Parola P., Shpynov S., Camicas J.L., Brouqui P., Caruso G., Raoult D. Genetic diversity of bacterial agents detected in ticks removed from asymptomatic patients in Northeastern Italy. Ann. N.Y. Acad. Sci., 2003, no. 990, pp. 182–190. doi: 10.1111/j.1749-6632.2003.tb07360.x36.Sassera D., Beninati T., Bandi C., Bouman E.A., Sacchi L., Fabbi M., Lo N. “Candidatus Midichloria mitochondrii”, an endo-symbiont of the tick Ixodes ricinus with a unique intramitochondrial lifestyle. Int. J. Syst. Evol. Microbiol., 2006, no. 56, pp. 2535– 2540. doi: 10.1099/ijs.0.64386-037.Sassera D., Lo N., Bouman E.A., Epis S., Mortarino M., Bandi C. “Candidatus Midichloria” endosymbionts bloom after the blood meal of the host, the hard tick Ixodes ricinus. Appl. Environ. Microbiol., 2008, no. 74, pp. 6138–6140. doi: 10.1128/AEM.00248-0838.Sassera D., Lo N., Epis S., D’Auria G., Montagna M., Comandatore F., Horner D., Pereto J., Luciano A.M., Franciosi F., Ferri E., Crotti E., Bazzocchi C., Daffonchio D., Sacchi L., Moya A., Latorre A., Bandi C. Phylogenomic evidence for the presence of a flagellum and cbb(3) oxidase in the free-living mitochondrial ancestor. Mol. Biol. Evol., 2011, no. 28, pp. 3285–3296. doi: 10.1093/molbev/msr15939.Schrallhammer M., Ferrantini F., Vannini C., Galati S., Schweikert M., Görtz H.D., Verni F., Petroni G. “Candidatus Megaira polyxenophila” gen. nov., sp. nov.: considerations on evolutionary history, host range and shift of early divergent rickettsiae. PLoS One, 2013, vol. 8, iss. 8:e72581. doi: 10.1371/journal.pone.007240.Shpynov S. Ixodes persulcatus, a major vector of Alphaproteobacteria in Russia. Ticks Tick-borne Dis., 2012, no. 3, pp. 304–306. doi: 10.1016/j.ttbdis.2012.10.02941.Skarphedinsson S., Jensen P.M., Kristiansen K. Survey of tickborne infections in Denmark. Emerg. Infect. Dis., 2005, no. 11, pp. 1055–1061. doi: 10.3201/eid1107.04126542.Szokoli F., Sabaneyeva E., Castelli M., Krenek S., Schrallhammer M., Soares C.A., Da Silva-Neto I.D., Berendonk T.U., Petroni G. “Candidatus Fokinia solitaria”, a novel “stand-alone” symbiotic lineage of Midichloriaceae (Rickettsiales). PLoS One, 2016, no. 11:e0145743. doi: 10.1371/journal.pone.014574343.Toft C., Fares M.A. The evolution of the flagellar assembly pathway in endosymbiotic bacterial genomes. Mol. Biol. Evol., 2008, no. 25, pp. 2069–2076. doi: 10.1093/molbev/msn15344.Vannini C., Ferrantini F., Schleifer K.H., Ludwig W., Verni F., Petroni G. “Candidatus anadelfobacter veles” and “Candidatus Cyrtobacter comes” two new rickettsiales species hosted by the protist ciliate Euplotes harpa (Ciliophora, Spirotrichea). Appl. Environ. Microbiol., 2010, no. 76, pp. 4047–4054. doi: 10.1128/AEM.03105-0945.Williams-Newkirk A.J., Rowe L.A., Mixson-Hayden T.R., Gregory A.D. Presence, genetic variability, and potential significance of “Candidatus Midichloria mitochondrii” in the lone star tick Amblyomma americanum. Exp. Appl. Acarol., 2012, no. 58, pp. 291–300. doi: 10.1007/s10493-012-9582-546.Zhu Z., Aeschlimann A., Gern L. Rickettsia-like microorganisms in the ovarian primordia of molting Ixodes ricinus (Acari: Ixodidae) larvae and nymphs. Ann. Parasitol. Hum. Comp., 1992, no. 67, pp. 99–110.