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2025年5月28日 周三
首页 > 过刊浏览>2024年第51卷第8期 >2809-2818. DOI:10.13344/j.microbiol.china.240035
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人布鲁氏菌病致病机制及治疗研究进展
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黑龙江省卫生健康委科技计划(20221212071181)


Research progress in the pathogenesis and treatment of human brucellosis
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    摘要:

    人布鲁氏菌病(布病)是由兼性细胞内病原体布鲁氏菌(Brucella)引起的一种人畜共患病。人常通过直接接触受感染的动物或食用动物产品而获得感染。布鲁氏菌病因其临床表现不特异，治疗不及时易转为慢性，严重影响患者的生存质量。因此，了解病原体致病特点、与宿主细胞的相互作用机制和治疗现状可为临床诊疗提供新方向。本文阐述了布鲁氏菌感染机制、宿主(人)先天性及适应性反应机制，以及目前布鲁氏菌病临床特点和治疗方略，为人布鲁氏菌防治提供参考。

    Abstract:

    Human brucellosis is a zoonotic disease caused by the facultative intracellular pathogen Brucella. Humans often become infected through direct contact with infected animals or by eating animal products. Because of the unspecific clinical manifestations, brucellosis is easy to become chronic without timely diagnosis and treatment, which seriously affects the quality of life of the patients. Therefore, understanding the pathogenic characteristics of the pathogen, the mechanism of host-pathogen interaction, and the current treatment status can provide a new direction for the clinical diagnosis and treatment of brucellosis. This paper describes the infection mechanism of Brucella, the innate and adaptive response mechanisms of the host (human), and the current clinical characteristics and treatment strategies of brucellosis, aiming to provide reference for the prevention and treatment of human brucellosis.

    参考文献
    [1] MORENO E, CLOECKAERT A, MORIYÓN I. Brucella evolution and taxonomy[J]. Veterinary Microbiology, 2002, 90(1/2/3/4): 209-227.
    [2] CLOECKAERT A, VERGER JM, GRAYON M, PAQUET JY, GARIN-BASTUJI B, FOSTER G, GODFROID J. Classification of Brucella spp. isolated from marine mammals by DNA polymorphism at the omp2 locus[J]. Microbes and Infection, 2001, 3(9): 729-738.
    [3] SCHOLZ HC, HUBALEK Z, SEDLÁCEK I, VERGNAUD G, TOMASO H, AL DAHOUK S, MELZER F, KÄMPFER P, NEUBAUER H, CLOECKAERT A, MAQUART M, ZYGMUNT MS, WHATMORE AM, FALSEN E, BAHN P, GÖLLNER C, PFEFFER M, HUBER B, BUSSE HJ, NÖCKLER K. Brucella microti sp. nov., isolated from the common vole Microtus arvalis[J]. International Journal of Systematic and Evolutionary Microbiology, 2008, 58(Pt 2): 375-382.
    [4] APARICIO ED. Epidemiology of brucellosis in domestic animals caused by Brucella melitensis, Brucella suis and Brucella abortus[J]. Revue Scientifique et Technique (International Office of Epizootics), 2013, 32(1): 43-51, 53-60.
    [5] KAUFMANN AF, FOX MD, BOYCE JM, ANDERSON DC, POTTER ME, MARTONE WJ, PATTON CM. Airborne spread of brucellosis[J]. Annals of the New York Academy of Sciences, 1980, 353: 105-114.
    [6] PEREIRA CR, de ALMEIDA JVFC, de OLIVEIRA IRC, de OLIVEIRA LF, PEREIRA LJ, ZANGERÔNIMO MG, LAGE AP, DORNELES EMS. Occupational exposure to Brucella spp.: a systematic review and meta-analysis[J]. PLoS Neglected Tropical Diseases, 2020, 14(5): e0008164.
    [7] HUY TXN, NGUYEN TT, KIM H, REYES AWB, KIM S. Brucella phagocytosis mediated by pathogen-host interactions and their intracellular survival[J]. Microorganisms, 2022, 10(10): 2003.
    [8] COPIN R, VITRY MA, MAMBRES DH, MACHELART A, de TREZ C, VANDERWINDEN JM, MAGEZ S, AKIRA S, RYFFEL B, CARLIER Y, LETESSON JJ, MURAILLE E. In situ microscopy analysis reveals local innate immune response developed around Brucella infected cells in resistant and susceptible mice[J]. PLoS Pathogens, 2012, 8(3): e1002575.
    [9] KÖHLER S, MICHAUX-CHARACHON S, PORTE F, RAMUZ M, LIAUTARD JP. What is the nature of the replicative niche of a stealthy bug named Brucella?[J]. Trends in Microbiology, 2003, 11(5): 215-219.
    [10] von BARGEN K, GORVEL JP, SALCEDO SP. Internal affairs: investigating the Brucella intracellular lifestyle[J]. FEMS Microbiology Reviews, 2012, 36(3): 533-562.
    [11] CELLI J, de CHASTELLIER C, FRANCHINI DM, PIZARRO-CERDA J, MORENO E, GORVEL JP. Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum[J]. The Journal of Experimental Medicine, 2003, 198(4): 545-556.
    [12] STARR T, CHILD R, WEHRLY TD, HANSEN B, HWANG S, LÓPEZ-OTIN C, VIRGIN HW, CELLI J. Selective subversion of autophagy complexes facilitates completion of the Brucella intracellular cycle[J]. Cell Host & Microbe, 2012, 11(1): 33-45.
    [13] KO J, GENDRON-FITZPATRICK A, SPLITTER GA. Susceptibility of IFN regulatory factor-1 and IFN consensus sequence binding protein-deficient mice to brucellosis[J]. Journal of Immunology, 2002, 168(5): 2433-2440.
    [14] URIBE-QUEROL E, ROSALES C. Control of phagocytosis by microbial pathogens[J]. Frontiers in Immunology, 2017, 8: 1368.
    [15] JEAN C. The intracellular life cycle of Brucella spp.[J]. Microbiology Spectrum, 2019, 7(2): 10.1128/ microbiolspec.BAI-10.1128/microbiolspec0006-2019.
    [16] STARR T, NG TW, WEHRLY TD, KNODLER LA, CELLI J. Brucella intracellular replication requires trafficking through the late endosomal/lysosomal compartment[J]. Traffic, 2008, 9(5): 678-694.
    [17] DIACOVICH L, GORVEL JP. Bacterial manipulation of innate immunity to promote infection[J]. Nature Reviews Microbiology, 2010, 8: 117-128.
    [18] ATLURI VL, XAVIER MN, de JONG MF, den HARTIGH AB, TSOLIS RM. Interactions of the human pathogenic Brucella species with their hosts[J]. Annual Review of Microbiology, 2011, 65: 523-541.
    [19] BARRIONUEVO P, DELPINO MV, VELÁSQUEZ LN, SAMARTINO CG, CORIA LM, IBAÑEZ AE, RODRÍGUEZ ME, CASSATARO J, GIAMBARTOLOMEI GH. Brucella abortus inhibits IFN-γ-induced FcγRI expression and FcγRI-restricted phagocytosis via toll-like receptor 2 on human monocytes/macrophages[J]. Microbes and Infection, 2011, 13(3): 239-250.
    [20] ANDERSEN-NISSEN E, SMITH KD, STROBE KL, RASSOULIAN BARRETT SL, COOKSON BT, LOGAN SM, ADEREM A. Evasion of Toll-like receptor 5 by flagellated bacteria[J]. Proceedings of the National Academy of Sciences of the United States of America, 2005, 102(26): 9247-9252.
    [21] LIU Z, SHEN TF, WEI DW, YU Y, HUANG DS, GUAN P. Analysis of the epidemiological, clinical characteristics, treatment and prognosis of human brucellosis during 2014–2018 in Huludao, China[J]. Infection and Drug Resistance, 2020, 13: 435-445.
    [22] BARQUERO-CALVO E, CHAVES-OLARTE E, WEISS DS, GUZMÁN-VERRI C, CHACÓN-DÍAZ C, RUCAVADO A, MORIYÓN I, MORENO E. Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection[J]. PLoS One, 2007, 2(7): e631.
    [23] CHACÓN-DÍAZ C, ALTAMIRANO-SILVA P, GONZÁLEZ-ESPINOZA G, MEDINA MC, ALFARO- ALARCÓN A, BOUZA-MORA L, JIMÉNEZ-ROJAS C, WONG M, BARQUERO-CALVO E, ROJAS N, GUZMÁN-VERRI C, MORENO E, CHAVES- OLARTE E. Brucella canis is an intracellular pathogen that induces a lower proinflammatory response than smooth zoonotic counterparts[J]. Infection and Immunity, 2015, 83(12): 4861-4870.
    [24] OLT S, ERGENÇ HS, AÇıKGÖZ SB. Predictive contribution of neutrophil/lymphocyte ratio in diagnosis of brucellosis[J]. BioMed Research International, 2015, 2015: 210502.
    [25] MORENO E, BARQUERO-CALVO E. The role of neutrophils in brucellosis[J]. Microbiology and Molecular Biology Reviews: MMBR, 2020, 84(4): e00048-20.
    [26] SALCEDO SP, MARCHESINI MI, LELOUARD H, FUGIER E, JOLLY G, BALOR S, MULLER A, LAPAQUE N, DEMARIA O, ALEXOPOULOU L, COMERCI DJ, UGALDE RA, PIERRE P, GORVEL JP. Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btp1[J]. PLoS Pathogens, 2008, 4(2): e21.
    [27] SALMERÓN I, RODRÍGUEZ-ZAPATA M, SALMERÓN O, MANZANO L, VAQUER S, ALVAREZ-MON M. Impaired activity of natural killer cells in patients with acute brucellosis[J]. Clinical Infectious Diseases: an Official Publication of the Infectious Diseases Society of America, 1992, 15(5): 764-770.
    [28] BALDWIN CL, GOENKA R. Host immune responses to the intracellular bacteria Brucella: does the bacteria instruct the host to facilitate chronic infection?[J]. Critical Reviews in Immunology, 2006, 26(5): 407-442.
    [29] WATARAI M, MAKINO SI, FUJII Y, OKAMOTO K, SHIRAHATA T. Modulation of Brucella-induced macropinocytosis by lipid rafts mediates intracellular replication[J]. Cellular Microbiology, 2002, 4(6): 341-355.
    [30] MARTIROSYAN A, MORENO E, GORVEL JP. An evolutionary strategy for a stealthy intracellular Brucella pathogen[J]. Immunological Reviews, 2011, 240(1): 211-234.
    [31] GRILLÓ MJ, BLASCO JM, GORVEL JP, MORIYÓN I, MORENO E. What have we learned from brucellosis in the mouse model?[J]. Veterinary Research, 2012, 43(1): 29.
    [32] KAPSENBERG ML. Dendritic-cell control of pathogen-driven T-cell polarization[J]. Nature Reviews Immunology, 2003, 3: 984-993.
    [33] BILLARD E, DORNAND J, GROSS A. Brucella suis prevents human dendritic cell maturation and antigen presentation through regulation of tumor necrosis factor alpha secretion[J]. Infection and Immunity, 2007, 75(10): 4980-4989.
    [34] DURWARD M, RADHAKRISHNAN G, HARMS J, BAREISS C, MAGNANI D, SPLITTER GA. Active evasion of CTL mediated killing and low quality responding CD8+ T cells contribute to persistence of brucellosis[J]. PLoS One, 2012, 7(4): e34925.
    [35] PASQUALI P, THORNTON AM, VENDETTI S, PISTOIA C, PETRUCCI P, TARANTINO M, PESCIAROLI M, RUGGERI F, BATTISTONI A, SHEVACH EM. CD4+CD25+ T regulatory cells limit effector T cells and favor the progression of brucellosis in BALB/c mice[J]. Microbes and Infection, 2010, 12(1): 3-10.
    [36] GAO N, JENNINGS P, GUO YH, YUAN D. Regulatory role of natural killer (NK) cells on antibody responses to Brucella abortus[J]. Innate Immunity, 2011, 17(2): 152-163.
    [37] SPERA JM, COMERCI DJ, UGALDE JE. Brucella alters the immune response in a prpA-dependent manner[J]. Microbial Pathogenesis, 2014, 67/68: 8-13.
    [38] KIANMEHR Z, SOLEIMANJAHI H, ARDESTANI SK, FOTOUHI F, ABDOLI A. Influence of Brucella abortus lipopolysaccharide as an adjuvant on the immunogenicity of HPV-16 L1VLP vaccine in mice[J]. Medical Microbiology and Immunology, 2015, 204(2): 205-213.
    [39] 白常乐. 布氏菌病再感染时的流行病学和临床-实验诊断特点[J]. 地方病译丛, 1989(3): 16-18. BAI CL. Epidemiological and clinical-experimental diagnostic characteristics of brucellosis reinfection[J]. Translation of Endemic Diseases, 1989(3): 16-18 (in Chinese).
    [40] 孙天志. 布鲁氏菌病的再感染[J]. 地方病译丛, 1980(2): 45-46. SUN TZ. Reinfection of brucellosis[J]. Translation of Endemic Diseases, 1980(2): 45-46 (in Chinese).
    [41] FAO, WHO. Joint FAO/WHO expert committee on brucellosis[M]. World Health Organization Technical Report Series, 1986, 740: 1-132.
    [42] ROUSHAN MRH, MOHRAZ M, HAJIAHMADI M, RAMZANI A, VALAYATI AA. Efficacy of Gentamicin plus Doxycycline versus Streptomycin plus Doxycycline in the Treatment of Brucellosis in Humans[J]. Clinical Infectious Diseases, 2006, 42(8): 1075-1080.
    [43] ALAVI SM, ALAVI L. Treatment of brucellosis: a systematic review of studies in recent twenty years[J]. Caspian Journal of Internal Medicine, 2013, 4(2): 636-641.
    [44] del POZO JSG, SOLERA J. Systematic review and meta-analysis of randomized clinical trials in the treatment of human brucellosis[J]. PLoS One, 2012, 7(2): e32090.
    [45] KUNJACHAN S, JOSE S, THOMAS CA, JOSEPH E, KIESSLING F, LAMMERS T. Physicochemical and biological aspects of macrophage-mediated drug targeting in anti-microbial therapy[J]. Fundamental & Clinical Pharmacology, 2012, 26(1): 63-71.
    [46] MODE S, KETTERER M, QUÉBATTE M, DEHIO C. Antibiotic persistence of intracellular Brucella abortus[J]. PLoS Neglected Tropical Diseases, 2022, 16(7): e0010635.
    [47] RAZEI A, JAVANBAKHT M, HAJIZADE A, HEIAT M, ZHAO S, AGHAMOLLAEI H, SAADATI M, KHAFAEI M, ASADI M, CEGOLON L, KEIHAN AH. Nano and microparticle drug delivery systems for the treatment of Brucella infections[J]. Biomedicine & Pharmacotherapy, 2023, 169: 115875.
    [48] GIULIETTI S, BIGINI V, SAVATIN DV. ROS and RNS production, subcellular localization, and signaling triggered by immunogenic danger signals[J]. Journal of Experimental Botany, 2023: erad449.
    [49] HOSSEINI SM, TAHERI M, NOURI F, FARMANI A, MOEZ NM, ARABESTANI MR. Nano drug delivery in intracellular bacterial infection treatments[J]. Biomedicine & Pharmacotherapy, 2022, 146: 112609.
    [50] BODAGHABADI N, HAJIGHOLAMI S, MALEKSHAHI ZV, ENTEZARI M, NAJAFI F, SHIRZAD H, SADEGHIZADEH M. Preparation and evaluation of rifampicin and co-trimoxazole-loaded nanocarrier against Brucella melitensis infection[J]. Iranian Biomedical Journal, 2018, 22(4): 275-282.
    [51] GHADERKHANI J, YOUSEFIMASHOUF R, ARABESTANI M, ROSHANAEI G, ASL SS, ABBASALIPOURKABIR R. Improved antibacterial function of Rifampicin-loaded solid lipid nanoparticles on Brucella abortus[J]. Artificial Cells, Nanomedicine, and Biotechnology, 2019, 47(1): 1181-1193.
    [52] WARETH G, DADAR M, ALI H, HAMDY MER, AL-TALHY AM, ELKHARSAWI AR, EL TAWAB AAA, NEUBAUER H. The perspective of antibiotic therapeutic challenges of brucellosis in the Middle East and North African countries: current situation and therapeutic management[J]. Transboundary and Emerging Diseases, 2022, 69(5): e1253-68.
    [53] IMBULUZQUETA E, GAMAZO C, LANA H, CAMPANERO MÁ, SALAS D, GIL AG, ELIZONDO E, VENTOSA N, VECIANA J, BLANCO-PRIETO MJ. Hydrophobic gentamicin-loaded nanoparticles are effective against Brucella melitensis infection in mice[J]. Antimicrobial Agents and Chemotherapy, 2013, 57(7): 3326-3333.
    [54] RAZEI A, CHERAGHALI AM, SAADATI M, RAMANDI MF, PANAHI Y, HAJIZADE A, SIADAT SD, BEHROUZI A. Gentamicin-loaded chitosan nanoparticles improve its therapeutic effects on Brucella-infected J774A.1 murine cells[J]. Galen Medical Journal, 2019, 8: e1296.
    [55] MITCHELL G, CHEN C, PORTNOY DA. Strategies used by bacteria to grow in macrophages[J]. Microbiology Spectrum, 2017: 701-725.
    [56] BOSCHIROLI ML, OUAHRANI-BETTACHE S, FOULONGNE V, MICHAUX-CHARACHON S, BOURG G, ALLARDET-SERVENT A, CAZEVIEILLE C, LIAUTARD JP, RAMUZ M, O’CALLAGHAN D. The Brucella suis virB operon is induced intracellularly in macrophages[J]. Proceedings of the National Academy of Sciences of the United States of America, 2002, 99(3): 1544-1549.
    [57] PORTE F, LIAUTARD JP, KÖHLER S. Early acidification of phagosomes containing Brucella suis is essential for intracellular survival in murine macrophages[J]. Infection and Immunity, 1999, 67(8): 4041-4047.
    [58] 魏雪梅, 赵亚娟, 郑丽丽. 羟氯喹药物全球专利布局与研发态势分析[J]. 科学观察, 2020, 15(5): 32-37. WEI XM, ZHAO YJ, ZHENG LL. Hydroxychloroquine development trend analysis from the perspective of patent[J]. Science Focus, 2020, 15(5): 32-37 (in Chinese).
    [59] KARIMITABAR Z, CHEGINI Z, SHOKOOHIZADEH L, MOEZ NM, ARABESTANI MR, HOSSEINI SM. Use of the quantum dot-labeled solid lipid nanoparticles for delivery of streptomycin and hydroxychloroquine: a new therapeutic approach for treatment of intracellular Brucella abortus infection[J]. Biomedicine & Pharmacotherapy, 2023, 158: 114116.
    [60] MAJZOOBI MM, HASHMI SH, EMAMI K, SOLTANIAN AR. Combination of doxycycline, streptomycin and hydroxychloroquine for short-course treatment of brucellosis: a single-blind randomized clinical trial[J]. Infection, 2022, 50(5): 1267-1271.
    [61] SAYAN M, KıLıC S, UYANıK MH. Epidemiological survey of rifampicin resistance in clinic isolates of Brucella melitensis obtained from all regions of Turkey[J]. Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy, 2012, 18(1): 41-46.
    [62] JOHANSEN TB, SCHEFFER L, JENSEN VK, BOHLIN J, FERUGLIO SL. Whole-genome sequencing and antimicrobial resistance in Brucella melitensis from a Norwegian perspective[J]. Scientific Reports, 2018, 8: 8538.
    [63] SHEVTSOV A, SYZDYKOV M, KUZNETSOV A, SHUSTOV A, SHEVTSOVA E, BERDIMURATOVA K, MUKANOV K, RAMANKULOV Y. Antimicrobial susceptibility of Brucella melitensis in Kazakhstan[J]. Antimicrobial Resistance and Infection Control, 2017, 6: 130.
    [64] ALAMIAN S, DADAR M, ETEMADI A, AFSHAR D, ALAMIAN MM. Antimicrobial susceptibility of Brucella spp. isolated from Iranian patients during 2016 to 2018[J]. Iranian Journal of Microbiology, 2019, 11(5): 363-367.
    [65] LIU ZG, DI DD, WANG M, LIU RH, ZHAO HY, PIAO DR, ZHAO ZZ, HAO YQ, DU YN, JIANG H, CUI BY, XIA XZ. In vitro antimicrobial susceptibility testing of human Brucella melitensis isolates from Ulanqab of Inner Mongolia, China[J]. BMC Infectious Diseases, 2018, 18(1): 43.
    [66] 杨晓雯, 姜霞, 安翠红, 孙长云, 李巧玲, 李文博, 蔡英桂, 姜海. 羊种布鲁氏菌分离株体外抗生素敏感性研究[J]. 疾病监测, 2021, 36(12): 1286-1290. YANG XW, JIANG X, AN CH, SUN CY, LI QL, LI WB, CAI YG, JIANG H. Sensitivity of Brucella melitensis isolates to antibiotics in vitro[J]. Disease Surveillance, 2021, 36(12): 1286-1290 (in Chinese).
    [67] MA HR, XU HJ, WANG X, BU ZY, YAO T, ZHENG ZR, SUN Y, JI X, LIU J. Molecular characterization and antimicrobial susceptibility of human Brucella in Northeast China[J]. Frontiers in Microbiology, 2023, 14: 1137932.
    [68] BALABAN NQ, HELAINE S, LEWIS K, ACKERMANN M, ALDRIDGE B, ANDERSSON DI, BRYNILDSEN MP, BUMANN D, CAMILLI A, COLLINS JJ, DEHIO C, FORTUNE S, GHIGO JM, HARDT WD, HARMS A, HEINEMANN M, HUNG DT, JENAL U, LEVIN BR, MICHIELS J, et al. Definitions and guidelines for research on antibiotic persistence[J]. Nature Reviews Microbiology, 2019, 17: 441-448.
    [69] 邢智锋, 吴群红, 金福芝, 石刚, 黄纯英. 1949–2009年黑龙江省人间布鲁氏菌病疫情分析[J]. 疾病监测, 2011, 26(11): 861-863. XING ZF, WU QH, JIN FZ, SHI G, HUANG CY. Human distribution of brucellosis’ in Heilongjiang Province, 1949–2009[J]. Disease Surveillance, 2011, 26(11): 861-863 (in Chinese).
    [70] 袁爽, 万晓宇, 唐磊, 尹世辉, 葛晶雪, 邢智锋. 黑龙江省2010–2019年人间布鲁氏菌病流行病学特征与空间聚集性分析[J]. 中国卫生工程学, 2022, 21(6): 889-893. YUAN S, WAN XY, TANG L, YIN SH, GE JX, XING ZF. Epidemiological characteristics and spatial aggregation of human brucellosis in Heilongjiang Province from 2010 to 2019[J]. Chinese Journal of Public Health Engineering, 2022, 21(6): 889-893 (in Chinese).
    [71] 葛晶雪, 尹世辉, 唐磊, 袁爽, 邢智锋. 2012–2022年黑龙江省人间布鲁氏菌病流行特征分析[J]. 中国卫生工程学, 2023, 22(6): 729-731, 736. GE JX, YIN SH, TANG L, YUAN S, XING ZF. Epidemiological characteristics of human brucellosis in Heilongjiang Province, 2012–2022[J]. Chinese Journal of Public Health Engineering, 2023, 22(6): 729-731, 736 (in Chinese).
    [72] QURESHI KA, PARVEZ A, FAHMY NA, ABDEL HADY BH, KUMAR S, GANGULY A, ATIYA A, ELHASSAN GO, ALFADLY SO, PARKKILA S, ASPATWAR A. Brucellosis: epidemiology, pathogenesis, diagnosis and treatment-a comprehensive review[J]. Annals of Medicine, 2023, 55(2): 2295398.
    [73] CZYŻ DM, JAIN-GUPTA N, SHUMAN HA, CROSSON S. A dual-targeting approach to inhibit Brucella abortus replication in human cells[J]. Scientific Reports, 2016, 6: 35835.
    [74] CHIARAVIGLIO L, KIRBY JE. High-throughput intracellular antimicrobial susceptibility testing of Legionella pneumophila[J]. Antimicrobial Agents and Chemotherapy, 2015, 59(12): 7517-7529.
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宫伟,葛晶雪,尹世辉,李梦奇,周澳,邢智锋,孙巍. 人布鲁氏菌病致病机制及治疗研究进展[J]. 微生物学通报, 2024, 51(8): 2809-2818

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  • 收稿日期:2024-01-11
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