microbeПроблемы особо опасных инфекцийProblems of Particularly Dangerous Infections0370-10692658-719XRussian Research Anti-Plague Institute “Microbe”10.21055/0370-1069-2022-4-29-40microbe-1758Research ArticleОБЗОРЫREVIEWSСовременные молекулярно-генетические методы и перспективы их применения для индикации и идентификации штаммов Yersinia pestisAdvanced Molecular-Genetic Methods and Prospects for Their Application for the Indication and Identification of Yersinia pestis Strainshttps://orcid.org/0000-0002-4115-9486НикифоровК. А.NikiforovK. A.

Никифоров Константин Алексеевич

Российская Федерация, 410005, Саратов, ул. Университетская, 46

Konstantin A. Nikiforov

46, Universitetskaya St., Saratov, 410005, Russian Federation.

rusrapi@microbe.ruФКУН «Российский научно-исследовательский противочумный институт «Микроб»РоссияRussian Research Anti-Plague Institute “Microbe”Russian Federation202211022023042940Copyright © Никифоров К.А., 20232023Никифоров К.А.Nikiforov K.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.microbe.ru/jour/article/view/1758

В обзоре представлен анализ литературных данных, посвященных применению разнообразных современных молекулярно-генетических методов для проведения индикации и идентификации штаммов Yersinia pestis, обладающих разными свойствами и степенью вирулентности, что обусловлено разнообразными природными условиями, в которых они циркулируют. Методы рассмотрены и с позиции перспективности их применения на трех уровнях (территориальном, региональном и федеральном) системы лабораторной диагностики инфекционных болезней в организациях Роспотребнадзора, для решения задачи поддержания санитарно-эпидемиологического благополучия населения страны. Рассмотрены основные группы методов: основанные на анализе длин рестрикционных фрагментов (рибо- и IS-типирование, пульс-гельэлектрофорез); основанные на анализе специфических фрагментов (DFR-типирование, VNTR-типирование); основанные на секвенировании (MLST, CRISPR-анализ, SNP-анализ); ПЦР -методы (включая IPCR, SPA); методы изотермической амплификации (LAMP, HDA, RPA, SEA, PCA, SHERLOCK); ДНК‑ чипы; методы, использующие технологию аптамеров; био- и наносенсоры; ДНК - оригами; методы на основе нейронных сетей. В результате проведенного анализа можно сделать вывод о стремительном развитии молекулярной диагностики и генетики, которое направлено на повышение оперативности, многофакторности и упрощение применения с отсутствием необходимости в дорогостоящем оборудовании и высококвалифицированных кадрах для проведения анализа. На всех уровнях системы лабораторной диагностики инфекционных болезней в организациях Ропотребнадзора возможно использование методов, основанных на ПЦР, изотермической амплификации, SHERLOCK, биосенсорах, малогабаритных приборах для секвенирования. На территориальном уровне в противочумных станциях перспективным является использование иммуно‑ПЦР и SPA для проведения индикации Y. pestis. На региональном уровне многообещающим выглядит внедрение технологий, основанных на использовании аптамеров и ДНК‑ чипах. Для федерального уровня перспективно применение методов ДНК -оригами и новых технологий полногеномного секвенирования в рамках выполнения расширенной идентификации, молекулярного типирования и секвенирования геномов штаммов возбудителя чумы.

The review provides an analysis of the literature data on the use of various modern molecular-genetic methods for the indication and identification of Yersinia pestis strains with different properties and degree of virulence, which is caused by the diverse natural conditions in which they circulate. The methods are also considered from the perspective of their promising application at three levels (territorial, regional and federal) of the system for laboratory diagnosis of infectious diseases at the premises of Rospotrebnadzor organizations to solve the problem of maintaining the sanitary and epidemiological well-being of the country’s population. The main groups of methods considered are as follows: based on the analysis of the lengths of restriction fragments (ribo- and IS-typing, pulse gel electrophoresis); based on the analysis of specific fragments (DFR typing, VNTR typing); based on sequencing (MLST, CRISPR analysis, SNP analysis); PCR methods (including IPCR, SPA); isothermal amplification methods (LAMP, HDA, RPA, SEA, PCA, SHERLOCK); DNA-microarray; methods using aptamer technology; bio- and nano-sensors; DNA origami; methods based on neural networks. We can conclude that the rapid development of molecular diagnostics and genetics is aimed at increasing efficiency, multi-factorial approaches and simplifying the application of techniques with no need for expensive equipment and highly qualified personnel for analysis. At all levels of the system for laboratory diagnosis of infectious diseases at the Rospotrebnadzor organizations, it is possible to use methods based on PCR, isothermal amplification, SHERLOCK, biosensors, and small-sized sequencing devices. At the territorial level, at plague control stations, the use of immuno-PCR and SPA for the indication of Y. pestis is viable. At the regional level, introduction of the technologies based on the use of aptamers and DNA chips looks promising. For the federal level, the use of DNA origami methods and new technologies of whole genome sequencing is a prospect within the framework of advanced identification, molecular typing and sequencing of the genomes of plague agent strains.

возбудитель чумымолекулярно-генетические методыplague agentmolecular-genetic methodsReferencesОнищенко Г.Г., Смоленский В.Ю., Ежлова Е.Б., Демина Ю.В., Топорков В.П., Топорков А.В., Ляпин М.Н., Кутырев В.В. Концептуальные основы биологической безопасности. Часть 1. Вестник Российской академии медицинских наук. 2013; 10:4–13.Onishchenko G.G., Smolensky V.Yu., Ezhlova E.B., Demina Yu.V., Toporkov V.P., Toporkov A.V., Lyapin M.N., Kutyrev V.V. [Conceptual bases of biological safety. Part 1]. Vestnik Rossiyskoi Akademii Meditsinskikh Nauk [Bulletin of the Russian Academy of Medical Sciences]. 2013; (10):4–13.Онищенко Г.Г., Кутырев В.В., Кривуля С.Д., Федоров Ю.М., Топорков В.П. Стратегия борьбы с инфекционными болезнями и санитарная охрана территорий в современных условиях. Проблемы особо опасных инфекций. 2006; 2:5–9.Onishchenko G.G., Kutyrev V.V., Krivulya S.D., Fedorov Yu.M., Toporkov V.P. [Strategy for combating infectious diseases and sanitary protection of territories under modern conditions]. Problemy Osobo Opasnykh Infektsii [Problems of Particularly Dangerous Infections]. 2006; (2):5–9.Ерошенко Г.А., Краснов Я.М., Носов Н.Ю., Куклева Л.М., Никифоров К.А., Оглодин Е.Г., Кутырев В.В. Совершенствование подвидовой классификации Yersinia pestis на основе данных полногеномного секвенирования штаммов из России и сопредельных государств. Проблемы особо опасных инфекций. 2015; 4:58–64. DOI: 10.21055/0370-1069-2015-4-58-64.Eroshenko G.A., Krasnov Y.M., Nosov N.Yu., Kukleva L.M., Nikiforov K.A., Oglodin E.G., Kutyrev V.V. [Updating of intra-specific Yersinia pestis classification, based on the results of whole-genome sequencing of the strains from the Russian Federation and the neighboring states]. Problemy Osobo Opasnykh Infektsii [Problems of Particularly Dangerous Infections]. 2015; (4):58–64. DOI: 10.21055/0370-1069-2015-4-58-64.Kutyrev V.V., Eroshenko G.A., Motin V.L., Nosov N.Y., Krasnov J.M., Kukleva L.M., Nikiforov K.A., Al’khova Z.V., Oglodin E.G., Guseva N.P. Phylogeny and classification of Yersinia pestis through the lens of strains from the plague foci of Commonwealth of Independent States. Front. Microbiol. 2018; 9:1106. DOI: 10.3389/fmicb.2018.01106.Kutyrev V.V., Eroshenko G.A., Motin V.L., Nosov N.Y., Krasnov J.M., Kukleva L.M., Nikiforov K.A., Al’khova Z.V., Oglodin E.G., Guseva N.P. Phylogeny and classification of Yersinia pestis through the lens of strains from the plague foci of Commonwealth of Independent States. Front. Microbiol. 2018; 9:1106. DOI: 10.3389/fmicb.2018.01106.Никифоров К.А., Морозов О.А., Носов Н.Ю., Куклева Л.М., Ерошенко Г.А., Кутырев В.В. Популяционная структура, таксономия и генетические особенности штаммов Yersinia pestis центральноазиатского подвида. Генетика. 2018; 54(10):1125–35. DOI: 10.1134/S0016675818100107.Nikiforov K.A., Morozov O.A., Nosov N.Yu., Kukleva L.M., Eroshenko G.A., Kutyrev V.V. [Population structure, taxonomy and genetic features of Yersinia pestis strains of the Central Asian subspecies]. Genetika [Genetics]. 2018; 54(10):1125–35. DOI: 10.1134/S0016675818100107.Cui Y., Yu C., Yan Y., Li D., Li Y., Jombart T., Weinert L.A., Wang Z., Guo Z., Xu L., Zhang Y., Zheng H., Qin N., Xiao X., Wu M., Wang X., Zhou D., Qi Z., Du Z., Wu H., Yang X., Cao H., Wang H., Wang J., Yao S., Rakin A., Li Y., Falush D., Balloux F., Achtman M., Song Y., Wang J., Yang R. Historical variations in mutation rate in an epidemic pathogen, Yersinia pestis. Proc. Natl Acad. Sci. USA. 2013; 110(2):577–82. DOI: 10.1073/pnas.1205750110.Cui Y., Yu C., Yan Y., Li D., Li Y., Jombart T., Weinert L.A., Wang Z., Guo Z., Xu L., Zhang Y., Zheng H., Qin N., Xiao X., Wu M., Wang X., Zhou D., Qi Z., Du Z., Wu H., Yang X., Cao H., Wang H., Wang J., Yao S., Rakin A., Li Y., Falush D., Balloux F., Achtman M., Song Y., Wang J., Yang R. Historical variations in mutation rate in an epidemic pathogen, Yersinia pestis. Proc. Natl Acad. Sci. USA. 2013; 110(2):577–82. DOI: 10.1073/pnas.1205750110.Платонов М.Е., Евсеева В.В., Дентовская С.В., Анисимов А.П. Молекулярное типирование Yersinia pestis. Молекулярная генетика, микробиология и вирусология. 2013; 2:3–12.Platonov M.E., Evseeva V.V., Dentovskaya S.V., Anisimov A.P. [Molecular typing of Yersinia pestis]. Molekulyarnaya Genetika, Mikrobiologiya i Virusologiya [Molecular Genetics, Microbiology, and Virology]. 2013; (2):3–12.Zhang Y., Luo T., Yang C, Yue X., Guo R., Wang X., Buren M., Song Y., Yang R., Cao H., Cui Y., Dai X. Phenotypic and molecular genetic characteristics of Yersinia pestis at an emerging natural plague focus, Junggar Basin, China. Am. J. Trop. Med. Hyg. 2018; 98(1):231–7. DOI: 10.4269/ajtmh.17-0195.Zhang Y., Luo T., Yang C, Yue X., Guo R., Wang X., Buren M., Song Y., Yang R., Cao H., Cui Y., Dai X. Phenotypic and molecular genetic characteristics of Yersinia pestis at an emerging natural plague focus, Junggar Basin, China. Am. J. Trop. Med. Hyg. 2018; 98(1):231–7. DOI: 10.4269/ajtmh.17-0195.Wang P., Shi L., Zhang F., Guo Y., Zhang Z., Tan H., Cui Z., Ding Y., Liang Y., Liang Y., Yu D., Xu J., Li W., Song Z. Ten years of surveillance of the Yulong plague focus in China and the molecular typing and source tracing of the isolates. PLoS Negl. Trop. Dis. 2018; 12(3):e0006352. DOI: 10.1371/journal.pntd.0006352.Wang P., Shi L., Zhang F., Guo Y., Zhang Z., Tan H., Cui Z., Ding Y., Liang Y., Liang Y., Yu D., Xu J., Li W., Song Z. Ten years of surveillance of the Yulong plague focus in China and the molecular typing and source tracing of the isolates. PLoS Negl. Trop. Dis. 2018; 12(3):e0006352. DOI: 10.1371/journal.pntd.0006352.Nour El-Din H.T., Yassin A.S., Ragab Y.M., Hashem A.M. Phenotype-genotype characterization and antibiotic-resistance correlations among colonizing and infectious methicillin-resistant Staphylococcus aureus recovered from intensive care units. Infect. Drug. Resist. 2021; 14:1557–71. DOI: 10.2147/IDR.S296000.Nour El-Din H.T., Yassin A.S., Ragab Y.M., Hashem A.M. Phenotype-genotype characterization and antibiotic-resistance correlations among colonizing and infectious methicillin-resistant Staphylococcus aureus recovered from intensive care units. Infect. Drug. Resist. 2021; 14:1557–71. DOI: 10.2147/IDR.S296000.Jolley K.A., Maiden M.C. Using multilocus sequence typing to study bacterial variation: prospects in the genomic era. Future Microbiol. 2014; 9(5):623–30. DOI: 10.2217/fmb.14.24.Jolley K.A., Maiden M.C. Using multilocus sequence typing to study bacterial variation: prospects in the genomic era. Future Microbiol. 2014; 9(5):623–30. DOI: 10.2217/fmb.14.24.Grissa I., Vergnaud G., Pourcel C. Clustered regularly interspaced short palindromic repeats (CRISPRs) for the genotyping of bacterial pathogens. Methods Mol. Biol. 2009; 551:105–16. DOI: 10.1007/978-1-60327-999-4_9.Grissa I., Vergnaud G., Pourcel C. Clustered regularly interspaced short palindromic repeats (CRISPRs) for the genotyping of bacterial pathogens. Methods Mol. Biol. 2009; 551:105–16. DOI: 10.1007/978-1-60327-999-4_9.Spyrou M.A., Keller M., Tukhbatova R.I., Scheib C.L., Nelson E.A., Andrades Valtueña A., Neumann G.U., Walker D., Alterauge A., Carty N., Cessford C., Fetz H., Gourvennec M., Hartle R., Henderson M., von Heyking K., Inskip S.A., Kacki S., Key F.M., Knox E.L., Later C., Maheshwari-Aplin P., Peters J., Robb J.E., Schreiber J., Kivisild T., Castex D., Lösch S., Harbeck M., Herbig A., Bos K.I., Krause J. Phylogeography of the second plague pandemic revealed through analysis of historical Yersinia pestis genomes. Nat. Commun. 2019; 10(1):4470. DOI: 10.1038/s41467-019-12154-0.Spyrou M.A., Keller M., Tukhbatova R.I., Scheib C.L., Nelson E.A., Andrades Valtueña A., Neumann G.U., Walker D., Alterauge A., Carty N., Cessford C., Fetz H., Gourvennec M., Hartle R., Henderson M., von Heyking K., Inskip S.A., Kacki S., Key F.M., Knox E.L., Later C., Maheshwari-Aplin P., Peters J., Robb J.E., Schreiber J., Kivisild T., Castex D., Lösch S., Harbeck M., Herbig A., Bos K.I., Krause J. Phylogeography of the second plague pandemic revealed through analysis of historical Yersinia pestis genomes. Nat. Commun. 2019; 10(1):4470. DOI: 10.1038/s41467-019-12154-0.Chen F., Ye J., Liu W., Chio C., Wang W., Qin W. Knockout of a highly GC-rich gene in Burkholderia pyrrocinia by recombineering with freeze-thawing transformation. Mol. Plant Pathol. 2021; 22(7):843–57. DOI: 10.1111/mpp.13058.Chen F., Ye J., Liu W., Chio C., Wang W., Qin W. Knockout of a highly GC-rich gene in Burkholderia pyrrocinia by recombineering with freeze-thawing transformation. Mol. Plant Pathol. 2021; 22(7):843–57. DOI: 10.1111/mpp.13058.Yang S., Yuan Z.J., Zhu Y.H., Chen X., Wang W. lncRNA PVT1 promotes cetuximab resistance of head and neck squamous cell carcinoma cells by inhibiting miR-124-3p. Head Neck. 2021; 43(9):2712–23. DOI: 10.1002/hed.26742.Yang S., Yuan Z.J., Zhu Y.H., Chen X., Wang W. lncRNA PVT1 promotes cetuximab resistance of head and neck squamous cell carcinoma cells by inhibiting miR-124-3p. Head Neck. 2021; 43(9):2712–23. DOI: 10.1002/hed.26742.Mortazavipour M.M., Shahbazi S., Mahdian R. Detection of paternal IVS-II-1 (G>A) (HBB: c.315+1G>A) mutation in cell-free fetal DNA using COLD-PCR assay. Hemoglobin. 2020; 44(3):168–73. DOI: 10.1080/03630269.2020.1768864.Mortazavipour M.M., Shahbazi S., Mahdian R. Detection of paternal IVS-II-1 (G>A) (HBB: c.315+1G>A) mutation in cell-free fetal DNA using COLD-PCR assay. Hemoglobin. 2020; 44(3):168–73. DOI: 10.1080/03630269.2020.1768864.Kane S.R., Shah S.R., Alfaro T.M. Development of a rapid viability polymerase chain reaction method for detection of Yersinia pestis. J. Microbiol. Methods. 2019; 162:21–7. DOI: 10.1016/j.mimet.2019.05.005.Kane S.R., Shah S.R., Alfaro T.M. Development of a rapid viability polymerase chain reaction method for detection of Yersinia pestis. J. Microbiol. Methods. 2019; 162:21–7. DOI: 10.1016/j.mimet.2019.05.005.Siggillino A., Ulivi P., Pasini L., Reda M.S., Chiadini E., Tofanetti F.R., Baglivo S., Metro G., Crinó L., Delmonte A., Minotti V., Roila F., Ludovini V. Detection of EGFR mutations in plasma cell-free tumor DNA of TKI-treated advanced-NSCLC patients by three methodologies: Scorpion-ARMS, PNAClamp, and Digital PCR. Diagnostics (Basel). 2020; 10(12):1062. DOI: 10.3390/diagnostics10121062.Siggillino A., Ulivi P., Pasini L., Reda M.S., Chiadini E., Tofanetti F.R., Baglivo S., Metro G., Crinó L., Delmonte A., Minotti V., Roila F., Ludovini V. Detection of EGFR mutations in plasma cell-free tumor DNA of TKI-treated advanced-NSCLC patients by three methodologies: Scorpion-ARMS, PNAClamp, and Digital PCR. Diagnostics (Basel). 2020; 10(12):1062. DOI: 10.3390/diagnostics10121062.Schneider R., Lamien-Meda A., Auer H., Wiedermann-Schmidt U., Chiodini P.L., Walochnik J. Validation of a novel FRET real-time PCR assay for simultaneous quantitative detection and discrimination of human Plasmodium parasites. PLoS One. 2021; 16(6):e0252887. DOI: 10.1371/journal.pone.0252887.Schneider R., Lamien-Meda A., Auer H., Wiedermann-Schmidt U., Chiodini P.L., Walochnik J. Validation of a novel FRET real-time PCR assay for simultaneous quantitative detection and discrimination of human Plasmodium parasites. PLoS One. 2021; 16(6):e0252887. DOI: 10.1371/journal.pone.0252887.Sherrill-Mix S., Hwang Y., Roche A.M., Glascock A., Weiss S.R., Li Y., Haddad L., Deraska P., Monahan C., Kromer A., Graham-Wooten J., Taylor L.J., Abella B.S., Ganguly A., Collman R.G., Van Duyne G.D., Bushman F.D. Detection of SARS-CoV-2 RNA using RT-LAMP and molecular beacons. Genome Biol. 2021; 22(1):169. DOI: 10.1186/s13059-021-02387-y.Sherrill-Mix S., Hwang Y., Roche A.M., Glascock A., Weiss S.R., Li Y., Haddad L., Deraska P., Monahan C., Kromer A., Graham-Wooten J., Taylor L.J., Abella B.S., Ganguly A., Collman R.G., Van Duyne G.D., Bushman F.D. Detection of SARS-CoV-2 RNA using RT-LAMP and molecular beacons. Genome Biol. 2021; 22(1):169. DOI: 10.1186/s13059-021-02387-y.Никифоров К.А., Куклева Л.М., Ситмбетов Д.А., Осина Н.А., Ерошенко Г.А., Кутырев В.В. Конструирование набора реагентов «ГенПест-подвид/алтай-РГ Ф». Проблемы особо опасных инфекций. 2021; 4:90–5. DOI: 10.21055/0370-1069-2021-4-90-95.Nikiforov K.A., Kukleva L.M., Sitmbetov D.A., Osina N.A., Eroshenko G.A., Kutyrev V.V. [Construction of the reagent panel “GenPest-subspecies/Altai-RGF”]. Problemy Osobo Opasnykh Infektsii [Problems of Particularly Dangerous Infections]. 2021; (4):90–5. DOI: 10.21055/0370-1069-2021-4-90-95.Thomas M.C., Janzen T.W., Huscyzynsky G., Mathews A., Amoako K.K. Development of a novel multiplexed qPCR and Pyrosequencing method for the detection of human pathogenic yersiniae. Int. J. Food. Microbiol. 2017; 257:247–53. DOI: 10.1016/j.ijfoodmicro.2017.06.019.Thomas M.C., Janzen T.W., Huscyzynsky G., Mathews A., Amoako K.K. Development of a novel multiplexed qPCR and Pyrosequencing method for the detection of human pathogenic yersiniae. Int. J. Food. Microbiol. 2017; 257:247–53. DOI: 10.1016/j.ijfoodmicro.2017.06.019.Newton C.R., Graham A., Heptinstall L.E., Powell S.J., Summers C., Kalsheker N., Smith J.C., Markham A.F. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res. 1989; 17(7):2503–16. DOI: 10.1093/nar/17.7.2503.Newton C.R., Graham A., Heptinstall L.E., Powell S.J., Summers C., Kalsheker N., Smith J.C., Markham A.F. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res. 1989; 17(7):2503–16. DOI: 10.1093/nar/17.7.2503.Cai L., Kong F., Jelfs P., Gilbert G.L., Sintchenko V. Rolling circle amplification and multiplex allele-specific PCR for rapid detection of katG and inhA gene mutations in Mycobacterium tuberculosis. Int. J. Med. Microbiol. 2009; 299(8):574–81. DOI: 10.1016/j.ijmm.2009.05.006.Cai L., Kong F., Jelfs P., Gilbert G.L., Sintchenko V. Rolling circle amplification and multiplex allele-specific PCR for rapid detection of katG and inhA gene mutations in Mycobacterium tuberculosis. Int. J. Med. Microbiol. 2009; 299(8):574–81. DOI: 10.1016/j.ijmm.2009.05.006.Vogler A.J., Driebe E.M., Lee J., Auerbach R.K., Allender C.J., Stanley M., Kubota K., Andersen G.L., Radnedge L., Worsham P.L., Keim P., Wagner D.M. Assays for the rapid and specific identification of North American Yersinia pestis and the common laboratory strain CO92. Biotechniques. 2008; 44(2):201, 203–204, 207. DOI: 10.2144/000112815.Vogler A.J., Driebe E.M., Lee J., Auerbach R.K., Allender C.J., Stanley M., Kubota K., Andersen G.L., Radnedge L., Worsham P.L., Keim P., Wagner D.M. Assays for the rapid and specific identification of North American Yersinia pestis and the common laboratory strain CO92. Biotechniques. 2008; 44(2):201, 203–204, 207. DOI: 10.2144/000112815.Sano T., Smith C.L., Cantor C.R. Immuno-PCR: very sensitive antigen detection by means of specific antibody-DNA conjugates. Science. 1992; 258(5079):120–2. DOI: 10.1126/science.1439758.Sano T., Smith C.L., Cantor C.R. Immuno-PCR: very sensitive antigen detection by means of specific antibody-DNA conjugates. Science. 1992; 258(5079):120–2. DOI: 10.1126/science.1439758.Jayathilake C., Nemoto N. cDNA Display-mediated immuno-PCR (cD-IPCR): An ultrasensitive immunoassay for biomolecular detection. Methods Mol Biol. 2021; 2261:307–21. DOI: 10.1007/978-1-0716-1186-9_19.Jayathilake C., Nemoto N. cDNA Display-mediated immuno-PCR (cD-IPCR): An ultrasensitive immunoassay for biomolecular detection. Methods Mol Biol. 2021; 2261:307–21. DOI: 10.1007/978-1-0716-1186-9_19.Malou N., Tran T.N., Nappez C., Signoli M., Le Forestier C., Castex D., Drancourt M., Raoult D. Immuno-PCR – a new tool for paleomicrobiology: the plague paradigm. PLoS One. 2012; 7(2):e31744. DOI: 10.1371/journal.pone.0031744.Malou N., Tran T.N., Nappez C., Signoli M., Le Forestier C., Castex D., Drancourt M., Raoult D. Immuno-PCR – a new tool for paleomicrobiology: the plague paradigm. PLoS One. 2012; 7(2):e31744. DOI: 10.1371/journal.pone.0031744.Adessi C., Matton G., Ayala G., Turcatti G., Mermod J.J., Mayer P., Kawashima E. Solid phase DNA amplification: characterization of primer attachment and amplification mechanisms. Nucleic Acids Res. 2000; 28(20):E87. DOI: 10.1093/nar/28.20.e87.Adessi C., Matton G., Ayala G., Turcatti G., Mermod J.J., Mayer P., Kawashima E. Solid phase DNA amplification: characterization of primer attachment and amplification mechanisms. Nucleic Acids Res. 2000; 28(20):E87. DOI: 10.1093/nar/28.20.e87.Notomi T., Okayama H., Masubuchi H., Yonekawa T., Watanabe K., Amino N., Hase T. Loop-mediated isothermal amplification of DNA. Nucleic Acids Res. 2000; 28(12):E63. DOI: 10.1093/nar/28.12.e63.Notomi T., Okayama H., Masubuchi H., Yonekawa T., Watanabe K., Amino N., Hase T. Loop-mediated isothermal amplification of DNA. Nucleic Acids Res. 2000; 28(12):E63. DOI: 10.1093/nar/28.12.e63.Singh R., Pal V., Tripathi N.K., Goel A.K. Development of a pair of real-time loop mediated isothermal amplification assays for detection of Yersinia pestis, the causative agent of plague. Mol. Cell Probes. 2020; 54:101670. DOI: 10.1016/j.mcp.2020.101670.Singh R., Pal V., Tripathi N.K., Goel A.K. Development of a pair of real-time loop mediated isothermal amplification assays for detection of Yersinia pestis, the causative agent of plague. Mol. Cell Probes. 2020; 54:101670. DOI: 10.1016/j.mcp.2020.101670.Jin J., Duan L., Fu J., Chai F., Zhou Q., Wang Y., Shao X., Wang L., Yan M., Su X., Zhang Y., Pan J., Chen J. A real-time LAMP-based dual-sample microfluidic chip for rapid and simultaneous detection of multiple waterborne pathogenic bacteria from coastal waters. Anal. Methods. 2021; 13(24):2710–21. DOI: 10.1039/d1ay00492a.Jin J., Duan L., Fu J., Chai F., Zhou Q., Wang Y., Shao X., Wang L., Yan M., Su X., Zhang Y., Pan J., Chen J. A real-time LAMP-based dual-sample microfluidic chip for rapid and simultaneous detection of multiple waterborne pathogenic bacteria from coastal waters. Anal. Methods. 2021; 13(24):2710–21. DOI: 10.1039/d1ay00492a.Liu W., Dong D., Yang Z., Zou D., Chen Z., Yuan J., Huang L. Polymerase spiral reaction (PSR): A novel isothermal nucleic acid amplification method. Sci. Rep. 2015; 5:12723. DOI: 10.1038/srep12723.Liu W., Dong D., Yang Z., Zou D., Chen Z., Yuan J., Huang L. Polymerase spiral reaction (PSR): A novel isothermal nucleic acid amplification method. Sci. Rep. 2015; 5:12723. DOI: 10.1038/srep12723.Mayboroda O., Gonzalez Benito A., Sabaté del Rio J., Svobodova M., Julich S., Tomaso H., O’Sullivan C.K., Katakis I. Isothermal solid-phase amplification system for detection of Yersinia pestis. Anal. Bioanal. Chem. 2016; 408(3):671–6. DOI: 10.1007/s00216-015-9177-1.Mayboroda O., Gonzalez Benito A., Sabaté del Rio J., Svobodova M., Julich S., Tomaso H., O’Sullivan C.K., Katakis I. Isothermal solid-phase amplification system for detection of Yersinia pestis. Anal. Bioanal. Chem. 2016; 408(3):671–6. DOI: 10.1007/s00216-015-9177-1.Shi L., Yang G., Zhang Z., Xia L., Liang Y., Tan H., He J., Xu J., Song Z., Li W., Wang P. Reemergence of human plague in Yunnan, China in 2016. PLoS One. 2018; 13(6):e0198067. DOI: 10.1371/journal.pone.0198067.Shi L., Yang G., Zhang Z., Xia L., Liang Y., Tan H., He J., Xu J., Song Z., Li W., Wang P. Reemergence of human plague in Yunnan, China in 2016. PLoS One. 2018; 13(6):e0198067. DOI: 10.1371/journal.pone.0198067.Zasada A.A., Zacharczuk K., Formińska K., Wiatrzyk A., Ziółkowski R., Malinowska E. Isothermal DNA amplification combined with lateral flow dipsticks for detection of biothreat agents. Anal. Biochem. 2018; 560:60–6. DOI: 10.1016/j.ab.2018.09.008.Zasada A.A., Zacharczuk K., Formińska K., Wiatrzyk A., Ziółkowski R., Malinowska E. Isothermal DNA amplification combined with lateral flow dipsticks for detection of biothreat agents. Anal. Biochem. 2018; 560:60–6. DOI: 10.1016/j.ab.2018.09.008.Kortli S., Jauset-Rubio M., Tomaso H., Abbas M.N., Bashammakh A.S., El-Shahawi M.S., Alyoubi A.O., Ben-Ali M., O’Sullivan C.K. Yersinia pestis detection using biotinylated dNTPs for signal enhancement in lateral flow assays. Anal. Chim. Acta. 2020; 1112:54–61. DOI: 10.1016/j.aca.2020.03.059.Kortli S., Jauset-Rubio M., Tomaso H., Abbas M.N., Bashammakh A.S., El-Shahawi M.S., Alyoubi A.O., Ben-Ali M., O’Sullivan C.K. Yersinia pestis detection using biotinylated dNTPs for signal enhancement in lateral flow assays. Anal. Chim. Acta. 2020; 1112:54–61. DOI: 10.1016/j.aca.2020.03.059.Müller K., Daßen S., Holowachuk S., Zwirglmaier K., Stehr J., Buersgens F., Ullerich L., Stoecker K. Pulse-Controlled Amplification – A new powerful tool for on-site diagnostics under resource limited conditions. PLoS Negl. Trop. Dis. 2021; 15(1):e0009114. DOI: 10.1371/journal.pntd.0009114.Müller K., Daßen S., Holowachuk S., Zwirglmaier K., Stehr J., Buersgens F., Ullerich L., Stoecker K. Pulse-Controlled Amplification – A new powerful tool for on-site diagnostics under resource limited conditions. PLoS Negl. Trop. Dis. 2021; 15(1):e0009114. DOI: 10.1371/journal.pntd.0009114.Cunningham C.H., Hennelly C.M., Lin J.T., Ubalee R., Boyce R.M., Mulogo E.M., Hathaway N., Thwai K.L., Phanzu F., Kalonji A., Mwandagalirwa K., Tshefu A., Juliano J.J., Parr J.B. A novel CRISPR-based malaria diagnostic capable of Plasmodium detection, species differentiation, and drug-resistance genotyping. EBioMedicine. 2021; 68:103415. DOI: 10.1016/j.ebiom.2021.103415.Cunningham C.H., Hennelly C.M., Lin J.T., Ubalee R., Boyce R.M., Mulogo E.M., Hathaway N., Thwai K.L., Phanzu F., Kalonji A., Mwandagalirwa K., Tshefu A., Juliano J.J., Parr J.B. A novel CRISPR-based malaria diagnostic capable of Plasmodium detection, species differentiation, and drug-resistance genotyping. EBioMedicine. 2021; 68:103415. DOI: 10.1016/j.ebiom.2021.103415.Schermer B., Fabretti F., Damagnez M., Di Cristanziano V., Heger E., Arjune S., Tanner N.A., Imhof T., Koch M., Ladha A., Joung J., Gootenberg J.S., Abudayyeh O.O., Burst V., Zhang F., Klein F., Benzing T., Müller R.U. Rapid SARS-CoV-2 testing in primary material based on a novel multiplex RT-LAMP assay. PLoS One. 2020; 15(11):e0238612. DOI: 10.1371/journal.pone.0238612.Schermer B., Fabretti F., Damagnez M., Di Cristanziano V., Heger E., Arjune S., Tanner N.A., Imhof T., Koch M., Ladha A., Joung J., Gootenberg J.S., Abudayyeh O.O., Burst V., Zhang F., Klein F., Benzing T., Müller R.U. Rapid SARS-CoV-2 testing in primary material based on a novel multiplex RT-LAMP assay. PLoS One. 2020; 15(11):e0238612. DOI: 10.1371/journal.pone.0238612.Савватеева Е.Н., Дементьева Е.И., Цыбульская М.В., Осипова Т.В., Рябых Т.П., Турыгин А.Ю., Юрасов Р.А., Заседателев А.С., Рубина А.Ю. Биологический микрочип для одновременного количественного иммунологического анализа маркеров онкологических заболеваний в сыворотке крови человека. Бюллетень экспериментальной биологии и медицины. 2009; 6:679–83.Savvateeva E.N., Dement’eva E.I., Tsybul’skaya M.V., Osipova T.V., Ryabykh T.P., Turygin A.Yu., Yurasov R.A., Zasedatelev A.S., Rubina A.Yu. [Biological microchip for simultaneous quantitative immunological analysis of cancer markers in human blood serum]. Byulleten’ Eksperimental’noy Biologii i Meditsiny [Bulletin of Experimental Biology and Medicine]. 2009; 6:679–83.Jiang D., Tian Y., Zhang Y., Lu X., Xiao D., Zhou C. Onestep fast and label-free imaging array for multiplexed detection of trace avian influenza viruses. Anal. Chim. Acta. 2021; 1171:338645. DOI: 10.1016/j.aca.2021.338645.Jiang D., Tian Y., Zhang Y., Lu X., Xiao D., Zhou C. Onestep fast and label-free imaging array for multiplexed detection of trace avian influenza viruses. Anal. Chim. Acta. 2021; 1171:338645. DOI: 10.1016/j.aca.2021.338645.Srinivasan V., Stedtfeld R.D., Tourlousse D.M., Baushke S.W., Xin Y., Miller S.M., Pham T., Rouillard J.M., Gulari E., Tiedje J.M., Hashsham S.A. Diagnostic microarray for 14 water and foodborne pathogens using a flatbed scanner. J. Microbiol. Methods. 2017; 139:15–21. DOI: 10.1016/j.mimet.2017.04.009.Srinivasan V., Stedtfeld R.D., Tourlousse D.M., Baushke S.W., Xin Y., Miller S.M., Pham T., Rouillard J.M., Gulari E., Tiedje J.M., Hashsham S.A. Diagnostic microarray for 14 water and foodborne pathogens using a flatbed scanner. J. Microbiol. Methods. 2017; 139:15–21. DOI: 10.1016/j.mimet.2017.04.009.Никифоров К.А., Уткин Д.В., Макашова М.А., Куклева Л.М., Ерошенко Г.А., Кутырев В.В. Конструирование системы мультиплексных ПЦР с гибридизационно-флуоресцентным учетом результатов на твердой подложке для индикации и идентификации штаммов возбудителя чумы. Биотехнология. 2020; 36(3):46–56. DOI: 10.21519/0234-2758-2020-36-3-46-56.Nikiforov K.A., Utkin D.V., Makashova M.A., Kukleva L.M., Eroshenko G.A., Kutyrev V.V. [Construction of a multiplex PCR system with hybridization-fluorescence registration of results on a solid substrate for the indication and identification of plague agent strains]. Biotekhnologiya [Biotechnology]. 2020; 36(3):46–56. DOI: 10.21519/0234-2758-2020-36-3-46-56.Famulok M. Allosteric aptamers and aptazymes as probes for screening approaches. Curr. Opin. Mol. Ther. 2005; 7(2):137‒43.Famulok M. Allosteric aptamers and aptazymes as probes for screening approaches. Curr. Opin. Mol. Ther. 2005; 7(2):137‒43.Ellington A.D., Szostak J.W. In vitro selection of RNA molecules that bind specific ligands. Nature. 1990; 346(6287):818‒22. DOI: 10.1038/346818a0.Ellington A.D., Szostak J.W. In vitro selection of RNA molecules that bind specific ligands. Nature. 1990; 346(6287):818‒22. DOI: 10.1038/346818a0.Jeddi I., Saiz L. Computational design of single-stranded DNA hairpin aptamers immobilized on a biosensor substrate. Sci. Rep. 2021; 11(1):10984. DOI: 10.1038/s41598-021-88796-2.Jeddi I., Saiz L. Computational design of single-stranded DNA hairpin aptamers immobilized on a biosensor substrate. Sci. Rep. 2021; 11(1):10984. DOI: 10.1038/s41598-021-88796-2.Duanghathaipornsuk S., Reaver N.G.F., Cameron B.D., Kim D.S. Adsorption kinetics of glycated hemoglobin on aptamer microarrays with antifouling surface modification. Langmuir. 2021; 37(15):4647–57. DOI: 10.1021/acs.langmuir.1c00446.Duanghathaipornsuk S., Reaver N.G.F., Cameron B.D., Kim D.S. Adsorption kinetics of glycated hemoglobin on aptamer microarrays with antifouling surface modification. Langmuir. 2021; 37(15):4647–57. DOI: 10.1021/acs.langmuir.1c00446.Jalali T., Salehi-Vaziri M., Pouriayevali M.H., Gargari S.L.M. Aptamer based diagnosis of Crimean-Congo hemorrhagic fever from clinical specimens. Sci. Rep. 2021; 11(1):12639. DOI: 10.1038/s41598-021-91826-8.Jalali T., Salehi-Vaziri M., Pouriayevali M.H., Gargari S.L.M. Aptamer based diagnosis of Crimean-Congo hemorrhagic fever from clinical specimens. Sci. Rep. 2021; 11(1):12639. DOI: 10.1038/s41598-021-91826-8.Qlark L.C. Jr. Monitor and control of blood and tissue oxygen tensions. ASAIO J. 1956; 2(1):41–8.Qlark L.C. Jr. Monitor and control of blood and tissue oxygen tensions. ASAIO J. 1956; 2(1):41–8.Hong C.A., Park J.C., Na H., Jeon H., Nam Y.S. Short DNA-catalyzed formation of quantum dot-DNA hydrogel for enzymefree femtomolar specific DNA assay. Biosens Bioelectron. 2021; 182:113110. DOI: 10.1016/j.bios.2021.113110.Hong C.A., Park J.C., Na H., Jeon H., Nam Y.S. Short DNA-catalyzed formation of quantum dot-DNA hydrogel for enzymefree femtomolar specific DNA assay. Biosens Bioelectron. 2021; 182:113110. DOI: 10.1016/j.bios.2021.113110.Born F., Braun P., Scholz H.C., Grass G. Specific detection of Yersinia pestis based on receptor binding proteins of phages. Pathogens. 2020; 9(8):611. DOI: 10.3390/pathogens9080611.Born F., Braun P., Scholz H.C., Grass G. Specific detection of Yersinia pestis based on receptor binding proteins of phages. Pathogens. 2020; 9(8):611. DOI: 10.3390/pathogens9080611.Liu X., Wang L., Zhao J., Zhu Y., Yang J., Yang F. Enhanced binding efficiency of microcantilever biosensor for the detection of Yersinia. Sensors (Basel). 2019; 19(15):3326. DOI: 10.3390/s19153326.Liu X., Wang L., Zhao J., Zhu Y., Yang J., Yang F. Enhanced binding efficiency of microcantilever biosensor for the detection of Yersinia. Sensors (Basel). 2019; 19(15):3326. DOI: 10.3390/s19153326.Seeman N.C. Nucleic acid junctions and lattices. J. Theor. Biol. 1982; 99(2):237–47. DOI: 10.1016/0022-5193(82)90002-9.Seeman N.C. Nucleic acid junctions and lattices. J. Theor. Biol. 1982; 99(2):237–47. DOI: 10.1016/0022-5193(82)90002-9.Rothemund P.W. Folding DNA to create nanoscale shapes and patterns. Nature. 2006; 440(7082):297–302. DOI: 10.1038/nature04586.Rothemund P.W. Folding DNA to create nanoscale shapes and patterns. Nature. 2006; 440(7082):297–302. DOI: 10.1038/nature04586.Raveendran M., Lee A.J., Sharma R., Wälti C., Actis P. Rational design of DNA nanostructures for single molecule biosensing. Nat. Commun. 2020; 11(1):4384. DOI: 10.1038/s41467-020-18132-1.Raveendran M., Lee A.J., Sharma R., Wälti C., Actis P. Rational design of DNA nanostructures for single molecule biosensing. Nat. Commun. 2020; 11(1):4384. DOI: 10.1038/s41467-020-18132-1.Ochmann S.E., Vietz C., Trofymchuk K., Acuna G.P., Lalkens B., Tinnefeld P. Optical nanoantenna for single moleculebased detection of Zika virus nucleic acids without molecular multiplication. Anal. Chem. 2017; 89(23):13000–7. DOI: 10.1021/acs.analchem.7b04082.Ochmann S.E., Vietz C., Trofymchuk K., Acuna G.P., Lalkens B., Tinnefeld P. Optical nanoantenna for single moleculebased detection of Zika virus nucleic acids without molecular multiplication. Anal. Chem. 2017; 89(23):13000–7. DOI: 10.1021/acs.analchem.7b04082.Yang B., Zhang Z., Yang C., Wang Y., Orr M.C., Hongbin W., Zhang A.B. Identification of species by combining molecular and morphological data using convolutional neural networks. Syst. Biol. 2022; 71(3):690–705. DOI: 10.1093/sysbio/syab076.Yang B., Zhang Z., Yang C., Wang Y., Orr M.C., Hongbin W., Zhang A.B. Identification of species by combining molecular and morphological data using convolutional neural networks. Syst. Biol. 2022; 71(3):690–705. DOI: 10.1093/sysbio/syab076.

The authors declare that there are no conflicts of interest present.