猪链球菌生物被膜的形成及其耐药机制研究进展

doi:10.16431/j.cnki.1671-7236.2024.09.028

摘要/Abstract

摘要： 猪链球菌(Streptococcus suis)是一种能引起猪和人感染，危害较大的人兽共患病病原体。猪链球菌在自然状态下具有形成生物被膜的能力，是其产生耐药性的重要原因之一。目前已知猪链球菌是在感染的黏附、集结和分散3个阶段形成生物被膜，其中毒力因子(荚膜多糖、溶菌酶释放蛋白和溶血素)起到主要作用，整个形成过程由细菌细胞的信号转导系统进行调控。细菌群体感应(quorum-sensing,QS)系统是细菌胞内重要的信号转导系统，它对细菌生物被膜的形成具有显著的调控作用，并通过调控水平基因转移、复制、生物被膜形成等方式增强细菌耐药性，同时在增加细菌密度等方面发挥重要作用。生物被膜的形成能够增强猪链球菌的耐药性，其耐药机制主要涉及QS系统调控、胞外聚合物的形成、细胞外DNA作用、外排泵作用、生物被膜结构和水平基因转移。明确猪链球菌生物被膜的形成与调控及生物被膜引起耐药的机制，对猪链球菌的预防和治疗具有重要意义。化学消毒剂、高温、紫外线和臭氧均能破坏猪链球菌的生物被膜并杀灭细菌；使用抗生素或抗菌剂等化学合成药物能抑制生物被膜的形成或破坏生物被膜，从而达到杀灭细菌的作用，实现治疗猪链球菌感染的目的。此外，部分中药对猪链球菌的生物被膜有抑制和破坏作用，其活性成分具有抗耐药的特性，具有良好的开发前景。笔者对猪链球菌生物被膜的形成和调控机制及其引起的耐药机制的研究进展进行综述，并对目前的防治策略进行归纳总结，以期为猪链球菌的防控提供新的思路。

关键词: 猪链球菌; 生物被膜; 调控机制; 耐药机制; 药物防治

Abstract: Streptococcus suis is a zoonotic pathogen that poses a significant threat to both pigs and humans. Streptococcus suis has the ability to form biofilms in its natural state, which is one of the main factors contributing to its drug resistance.It is currently known that Streptococcus suis forms biofilm in the three stages of adhesion, aggregation and dispersion of infection, and its virulence factors (capsular poly saccharide, muramidase-released protein and suilysin) play a major role, and the whole formation process is regulated by the signal transduction system of bacterial cells.The quorum-sensing (QS) system is an important intracellular signaling transduction system in bacteria, which significantly regulates the formation of bacterial biofilms.It enhances bacterial drug resistance by regulating gene transfer, replication, biofilm formation, and plays an important role in increasing bacterial density.The formation of biofilms enhances the drug resistance of Streptococcus suis, and its drug resistance mechanism mainly involves the regulation of QS system, the formation of extracellular polymeric substances, extracellular DNA action, the role of efflux pumps, the structure of the biofilm and the horizontal gene transfer.Understanding the formation and regulation of Streptococcus suis biofilms and the mechanisms of drug resistance caused by biofilms is of great significance for the prevention and treatment of Streptococcus suis.Chemical disinfectants, high temperatures, ultraviolet light, and ozone can destroy the biofilms of Streptococcus suis and kill the bacteria.The use of antibiotics or antimicrobials and other chemical synthetic drugs can inhibit the formation of biofilm or destroy biofilm, so as to achieve the role of killing bacteria and achieve the purpose of treating Streptococcus suis infection.In addition, some traditional Chinese medicines have an inhibitory and destructive effect on the biofilms of Streptococcus suis, and their active ingredients have anti-drug-resistant properties, showing promising prospects for development.The author summarizes the research progress on the formation and regulation of Streptococcus suis biofilms and the mechanisms of drug resistance, and summarizes the current prevention and treatment strategies, in order to provide new ideas for the prevention and control of Streptococcus suis.

Key words: Streptococcus suis; biofilm; regulatory mechanism; drug resistance mechanism; drug treatment

中图分类号:

S852.61⁺1

陈翔宇, 黄元, 刘宝玲, 罗琴, 陆泳锟, 何振文, 刘丁语, 乔常宏, 王晓虎, 王刚, 白挨泉, 蔡汝健. 猪链球菌生物被膜的形成及其耐药机制研究进展[J]. 中国畜牧兽医, 2024, 51(9): 4002-4013.

CHEN Xiangyu, HUANG Yuan, LIU Baoling, LUO Qin, LU Yongkun, HE Zhenwen, LIU Dingyu, QIAO Changhong, WANG Xiaohu, WANG Gang, BAI Aiquan, CAI Rujian. Research Progress on Biofilm Formation and Its Drug Resistance Mechanism of Streptococcus suis[J]. China Animal Husbandry and Veterinary Medicine, 2024, 51(9): 4002-4013.

参考文献

[1] 王佳煜.四川地区猪链球菌的分离鉴定及部分生物学特性分析[D].成都：四川农业大学,2020. WANG J Y.Identification and analysis of some biological traits of Streptococcus suis in Sichuan area[D].Chengdu:Sichuan Agricultural University,2020.(in Chinese)
[2] HUONG V T,THANH L V,PHU V D,et al.Temporal and spatial association of Streptococcus suis infection in humans and porcine reproductive and respiratory syndrome outbreaks in pigs in Northern Vietnam[J].Epidemiology and Infection,2016,144(1):35-44.
[3] BESUNG I,SUARJANA I,AGUSTINA K K,et al.Isolation and identification of Streptococcus suis from sick pigs in Bali,Indonesia[J].BMC Research Notes,2019,12(1):795.
[4] WERINDER A,ASPAN A,BACKHANS A,et al. Streptococcus suis in Swedish grower pigs:Occurrence,serotypes,and antimicrobial susceptibility[J]. Acta Veterinaria Scandinavica,2020,62(1):36.
[5] GAO M,ZUO J,SHEN Y,et al.Modeling co-infection by Streptococcus suis and Haemophilus parasuis reveals influences on biofilm formation and host response[J].Animals (Basel),2023,13(9):1511.
[6] FLEMMING H C,WINGENDER J,SZEWZYK U,et al.Biofilms:An emergent form of bacterial life[J].Nature Reviews Microbiology,2016,14(9):563-575.
[7] COSTERTON J W.Introduction to biofilm[J].International Journal of Antimicrobial Agents,1999,11(3-4):217-221.
[8] ROY R,TIWARI M,DONELLI G,et al.Strategies for combating bacterial biofilms:A focus on anti-biofilm agents and their mechanisms of action[J]. Virulence,2018,9(1):522-554.
[9] CEPAS V,LOPEZ Y,MUNOZ E,et al.Relationship between biofilm formation and antimicrobial resistance in Gram-negative bacteria[J].Microbial Drug Resistance,2019,25(1):72-79.
[10] 汪洋.猪链球菌生物被膜形成及致病机理研究[D].南京：南京农业大学,2011. WANG Y.Study on biofilm formation and pathogenic mechanism of Streptococcus suis[D].Nanjing:Nanjing Agricultural University,2011.(in Chinese)
[11] YI L,JIN M,LI J,et al.Antibiotic resistance related to biofilm formation in Streptococcus suis[J].Applied Microbiology and Biotechnology,2020,104(20):8649-8660.
[12] 靳曼玉,李金朋,易力,等.猪链球菌生物被膜形成的耐药机制[J].微生物学报,2021,61(7):1829-1838. JIN M Y,LI J P,YI L,et al.Biofilm-associated drug resistance in Streptococcus suis[J].Acta Microbiologica Sinica,2021,61(7):1829-1838.(in Chinese)
[13] 王金玉.穿心莲内酯对猪链球菌生物被膜QS系统及毒力因子的影响[D].哈尔滨：东北农业大学,2018. WANG J Y.Effects of andrographolide on QS system and virulence factors of Streptococcus suis biofilm[D].Harbin:Northeast Agricultural University,2018.(in Chinese)
[14] 王畅.芦丁干预猪链球菌生物被膜形成对荚膜多糖含量和结构的影响[D].哈尔滨：东北农业大学,2018. WANG C.Effect of rutin on content and structure of capsular polysaccharide in Streptococcus suis biofilm formation[D].Harbin:Northeast Agricultural University,2018.(in Chinese)
[15] 张珊珊,宋静,王家俊,等.细菌生物膜的形成及抗菌肽抗生物膜活性的研究进展[J].动物营养学报,2021,33(12):6631-6640. ZHANG S S,SONG J,WANG J J,et al.Formation of bacterial biofilm and anti-biofilm activity of antimicrobial peptides[J].Chinese Journal of Animal Nutrition,2021,33(12):6631-6640.(in Chinese)
[16] MENG X,SHI Y,JI W,et al.Application of a bacteriophage lysin to disrupt biofilms formed by the animal pathogen Streptococcus suis[J].Applied and Environmental Microbiology,2011,77(23):8272-8279.
[17] 李天一,王英锋,张玫.细菌荚膜多糖的研究进展[J].中国人兽共患病学报,2015,31(12):1171-1176. LI T Y,WANG Y F,ZHANG M.Research progress on bacterial capsular polysaccharide[J].Chinese Journal of Zoonoses,2015,31(12):1171-1176.(in Chinese)
[18] 王帅.芦丁干预S.suis生物被膜的形成及其对cps基因簇和毒力基因表达的影响[D].哈尔滨：东北农业大学,2017. WANG S.Rutin inhibits the formation of S.suis biofilm and its effects on the expression of cps gene cluster and virulence genes[D].Harbin:Northeast Agricultural University,2017.(in Chinese)
[19] OKURA M,TAKAMATSU D,MARUYAMA F,et al.Genetic analysis of capsular polysaccharide synthesis gene clusters from all serotypes of Streptococcus suis:Potential mechanisms for generation of capsular variation[J].Applied and Environmental Microbiology,2013，79(8):2796-2806.
[20] 魏子贡.猪链球菌流行病学及其生物被膜形成机理研究[D].武汉：华中农业大学,2011. WEI Z G.Study on the epidemiology of Streptococcus suis and the merchanism of their biofilm formation[D].Wuhan:Huazhong Agricultural University,2011.(in Chinese)
[21] PARIDA M,POSADAS G,INOUE S,et al.Real-time reverse transcription loop-mediated isothermal amplification for rapid detection of West Nile virus[J].Journal of Clinical Microbiology,2004,42(1):257-263.
[22] 孙珂,倪艳秀,祝昊丹,等.猪链球菌4型分离株生物学特性研究[J].中国畜牧兽医,2019,46(1):80-88. SUN K,NI Y X,ZHU H D,et al.Study on biological characteristics of Streptococcus suis type 4 isolates[J].China Animal Husbandry & Veterinary Medicine,2019,46(1):80-88.(in Chinese)
[23] 曾巧英,陆承平.猪链球菌2型溶菌酶释放蛋白的黏附作用[J].南京农业大学学报,2002,25(4):67-71. ZENG Q Y,LU C P.Role as adhesin of muramidase released protein of Streptococcus suis type 2[J]. Journal of Nanjing Agricultural University,2002,25(4):67-71.(in Chinese)
[24] JACOBS A A,VAN DEN BERG A J,LOEFFEN P L.Protection of experimentally infected pigs by suilysin,the thiol-activated haemolysin of Streptococcus suis[J]. Veterinary Record,1996,139(10):225-228.
[25] LI X,LI Q,ZHANG Z,et al.Canagliflozin inhibited the activity of hemolysin and reduced the inflammatory response caused by Streptococcus suis[J].International Journal of Molecular Sciences,2023,24(17):13074.
[26] TENENBAUM T,ASMAT T M,SEITZ M,et al.Biological activities of suilysin:Role in Streptococcus suis pathogenesis[J].Future Microbiology,2016,11:941-954.
[27] JACOBS A A,LOEFFEN P L,VAN DEN BERG A J,et al.Identification,purification,and characterization of a thiol-activated hemolysin (suilysin) of Streptococcus suis[J].Infection and Immunity,1994,62(5):1742-1748.
[28] 任志强,郑玉玲,甘淑珍,等.猪溶血素突变体的构建及活性评价[J].细胞与分子免疫学杂志,2012,28(6):580-582. REN Z Q,ZHENG Y L,GAN S Z,et al.Construction and activities of suilysin mutants[J].Chinese Journal of Cellular and Molecular Immunology,2012,28(6):580-582.(in Chinese)
[29] 孙倩男,郑峰,周婷婷,等.金黄色葡萄球菌α-溶血素突变体H35A抑制α-溶血素的细胞毒性[J].南京医科大学学报(自然科学版),2017,37(3):293-297. SUN Q N,ZHENG F,ZHOU T T,et al.Staphylococcus aureus alpha-hemolysin mutant H35A inhibits alpha-hemolysin cytotoxicity[J].Journal of Nanjing Medical University (Natural Sciences),2017,37(3):293-297.(in Chinese)
[30] TU C,WANG Y,YI L,et al.Roles of signaling molecules in biofilm formation[J].Chinese Journal of Biotechnology,2019,35(4):558-566.
[31] PRUSS B M.Involvement of two-component signaling on bacterial motility and biofilm development[J].Journal of Bacteriology,2017,199(18):e00259-17.
[32] MATSUYAMA B Y,KRASTEVA P V,BARAQUET C,et al.Mechanistic insights into c-di-GMP-dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa[J].Proceedings of the National Academy of Sciences of the United States of America,2016,113(2):E209-E218.
[33] POLKADE A V,MANTRI S S,PATWEKAR U J,et al.Quorum sensing:An under-explored phenomenon in the phylum actinobacteria[J].Frontiers in Microbiology，2016,7:131.
[34] WANG Y,BIAN Z,WANG Y.Biofilm formation and inhibition mediated by bacterial quorum sensing[J].Applied Microbiology and Biotechnology,2022,106(19-20):6365-6381.
[35] LI J,FAN Q,JIN M,et al.Paeoniflorin reduce LuxS/AI-2 system-controlled biofilm formation and irulence in Streptococcus suis[J].Virulence,2021,12(1):3062-3073.
[36] TAYLOR P K,YEUNG A T,HANCOCK R E.Antibiotic resistance in Pseudomonas aeruginosa biofilms:Towards the development of novel anti-biofilm therapies[J].Journal of Biotechnology,2014,191:121-130.
[37] FERNÁNDEZ L,BREIDENSTEIN E B,HANCOCK R E.Creeping baselines and adaptive resistance to antibiotics[J].Drug Resistance Updates,2011,14(1):1-21.
[38] WANG Y,WANG Y,SUN L,et al.The LuxS/AI-2 system of Streptococcus suis[J].Applied Microbiology and Biotechnology,2018,102(17):7231-7238.
[39] LIU B,YI L,LI J,et al.Autoinducer-2 influences tetracycline resistance in Streptococcus suis by regulating the tet(M) gene via transposon Tn916[J].Research in Veterinary Science,2020,128:269-274.
[40] KARYGIANNI L,REN Z,KOO H,et al.Biofilm matrixome:Extracellular components in structured microbial communities[J].Trends in Microbiology,2020,28(8):668-681.
[41] KAVITAKE D,DEVI P B,DELATTRE C,et al.Exopolysaccharides produced by enterococcus genus—An overview[J].International Journal of Biological Macromolecules,2023,226:111-120.
[42] MA F,YI L,YU N,et al.Streptococcus suis serotype 2 biofilms inhibit the formation of Neutrophil extracellular traps[J].Frontiers in Cellular and Infection Microbiology,2017,7:86.
[43] WALTERS M R,ROE F,BUGNICOURT A,et al.Contributions of antibiotic penetration,oxygen limitation,and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin[J].Antimicrobial Agents and Chemotherapy,2003,47(1):317-323.
[44] VENKATESAN N,PERUMAL G,DOBLE M.Bacterial resistance in biofilm-associated bacteria[J].Future Microbiology,2015,10(11):1743-1750.
[45] HALL C W,MAH T F.Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria[J].FEMS Microbiology Reviews,2017,41(3):276-301.
[46] OKSHEVSKY M,MEYER R L.The role of extracellular DNA in the establishment,maintenance and perpetuation of bacterial biofilms[J].Critical Reviews in Microbiology,2015,41(3):341-352.
[47] CHIANG W C,NILSSON M,JENSEN P O,et al.Extracellular DNA shields against aminoglycosides in Pseudomonas aeruginosa biofilms[J].Antimicrobial Agents and Chemotherapy,2013,57(5):2352-2361.
[48] MULCAHY H,CHARRON-MAZENOD L,LEWENZA S.Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms[J].PLoS Pathogens,2008,4(11):e1000213.
[49] SOTO S M.Role of efflux pumps in the antibiotic resistance of bacteria embedded in a biofilm[J].Virulence,2013,4(3):223-229.
[50] KUMAR S,LEKSHMI M,PARVATHI A,et al.Functional and structural roles of the major facilitator superfamily bacterial multidrug efflux pumps[J].Microorganisms,2020,8(2):266.
[51] KUSAKIZAKO T,MIYAUCHI H,ISHITANI R,et al.Structural biology of the multidrug and toxic compound extrusion superfamily transporters[J].Biochimica et Biophysica Acta.Biomembranes,2020,1862(12):183154.
[52] LIU Y Y,CHEN C C.Computational analysis of the molecular mechanism of RamR mutations contributing to antimicrobial resistance in Salmonella enterica[J].Scientific Reports,2017,7(1):13418.
[53] NISHINO K,YAMAGUCHI A.Analysis of a complete library of putative drug transporter genes in Escherichia coli[J].Journal of Bacteriology,2001,183(20):5803-5812.
[54] TSUCHIYA H,DOKI S,TAKEMOTO M,et al.Structural basis for amino acid export by DMT superfamily transporter YddG[J].Nature,2016,534(7607):417-420.
[55] WANG F,LI D,ZHENG Z,et al.Reversal of ABCB1-related multidrug resistance by ERK5-IN-1[J].Journal of Experimental & Clinical Cancer Research,2020,39(1):50.
[56] CHANDER Y,OLIVEIRA S R,GOYAL S M.Identification of the tet(B) resistance gene in Streptococcus suis[J].Veterinary Journal,2011,189(3):359-360.
[57] CHU Y W,CHEUNG T K,CHU M Y,et al.Resistance to tetracycline,erythromycin and clindamycin in Streptococcus suis serotype 2 in Hong Kong[J].International Journal of Antimicrobial Agents,2009,34(2):181-182.
[58] CHAN Y Y,CHUA K L.The Burkholderia pseudomallei BpeAB-OprB efflux pump:Expression and impact on quorum sensing and virulence[J].Journal of Bacteriology，2005,187(14):4707-4719.
[59] DE KIEVIT T R,PARKINS M D,GILLIS R J,et al.Multidrug efflux pumps:Expression patterns and contribution to antibiotic resistance in Pseudomonas aeruginosa biofilms[J].Antimicrobial Agents and Chemotherapy,2001,45(6):1761-1770.
[60] DIGGLE S P,WINZER K,LAZDUNSKI A,et al.Advancing the quorum in Pseudomonas aeruginosa:MvaT and the regulation of N-acylhomoserine lactone production and virulence gene expression[J]. Journal of Bacteriology,2002,184(10):2576-2586.
[61] LI X Z,NIKAIDO H.Efflux-mediated drug resistance in bacteria[J].Drugs,2004,64(2):159-204.
[62] LI X Z,NIKAIDO H.Efflux-mediated drug resistance in bacteria:An update[J].Drugs,2009,69(12):1555-1623.
[63] DAS B,BHADRA R K.(p) ppGpp metabolism and antimicrobial resistance in bacterial pathogens[J].Frontiers in Microbiology,2020,11:563944.
[64] PABST B,PITTS B,LAUCHNOR E,et al.Gel-entrapped Staphylococcus aureus bacteria as models of biofilm infection exhibit growth in dense aggregates,oxygen limitation,antibiotic tolerance,and heterogeneous gene expression[J].Antimicrobial Agents and Chemotherapy,2016,60(10):6294-6301.
[65] SCOTT M,GUNDERSON C W,MATEESCU E M,et al.Interdependence of cell growth and gene expression:Origins and consequences[J].Science,2010,330(6007):1099-1102.
[66] UTTER D R,ORPHAN V J.Gifts hidden in shadowy genome islands[J].Cell,2023,186(1):5-7.
[67] DECHENE-TEMPIER M,MAROIS-CREHAN C,LIBANTE V,et al.Update on the mechanisms of antibiotic resistance and the mobile resistome in the emerging zoonotic pathogen Streptococcus suis[J].Microorganisms,2021,9(8):1765.
[68] DUTKIEWICZ J,ZAJAC V,SROKA J,et al.Streptococcus suis:A re-emerging pathogen associated with occupational exposure to pigs or pork products.Part Ⅱ-Pathogenesis[J].Annals of Agricultural and Environmental Medicine,2018,25(1):186-203.
[69] MADSEN J S,BURMOLLE M,HANSEN L H,et al.The interconnection between biofilm formation and horizontal gene transfer[J].FEMS Immunology and Medical Microbiology,2012,65(2):183-195.
[70] RODRIGUEZ-BELTRAN J,DELAFUENTE J,LEON-SAMPEDRO R,et al.Beyond horizontal gene transfer:The role of plasmids in bacterial evolution[J].Nature Reviews Microbiology,2021,19(6):347-359.
[71] ARNOLD B J,HUANG I T,HANAGE W P.Horizontal gene transfer and adaptive evolution in bacteria[J].Nature Reviews Microbiology,2022,20(4):206-218.
[72] SEITZ M,VALENTIN-WEIGAND P,WILLENBORG J.Use of antibiotics and antimicrobial resistance in veterinary medicine as exemplified by the swine pathogen Streptococcus suis[J].Current Topics in Microbiology and Immunology,2016,398:103-121.
[73] 黄钰骄.海盐消毒剂杀菌性能及其机理初步研究[D].天津：天津工业大学,2021. HUANG Y J.Preliminary study on bactericidal performance and mechanism of sea salt disinfectant[D].Tianjin:Tianjin Industrial University,2021.(in Chinese)
[74] 安江珊,王利妍,刘琨毅,等.晒青茶灭菌方法研究[J].轻工学报,2022,37(1):40-45. AN J S,WANG L Y,LIU K Y,et al.Study of sterilization methods for sun-dried green tea[J].Journal of Light Industry,2022,37(1):40-45.(in Chinese)
[75] 张治国.紫外消毒对污水处理厂二级出水中抗生素抗性菌和抗性基因去除的影响和机理研究[D].南京:东南大学,2019. ZHANG Z G.Effects and mechanisms of UV disinfectionon the removal of antibiotic-resistantbacteria and antibiotic resistance genes insecondary effluent from wastewater treatment plants[D].Nanjing:Southeast University,2019.(in Chinese)
[76] PILETIC K,KOVAC B,PERCIC M,et al.Disinfecting action of gaseous ozone on OXA-48-producing Klebsiella pneumoniae biofilm in vitro[J].International Journal of Environmental Research and Public Health,2022,19(10):6177.
[77] ZUO J,FAN Q,LI J,et al.Sub-inhibitory concentrations of amoxicillin and tylosin affect the biofilm formation and virulence of Streptococcus suis[J].International Journal of Environmental Research and Public Health,2022,19(14):8359.
[78] LAN T,GUO Q,SHEN X.Polyethyleneimine and quaternized ammonium polyethyleneimine:The versatile materials for combating bacteria and biofilms[J].Journal of Biomaterials Science-polymer Edition,2019,30(14):1243-1259.
[79] CHEN D,ZHAO T,DOYLE M P.Control of pathogens in biofilms on the surface of stainless steel by levulinic acid plus sodium dodecyl sulfate[J].International Journal of Food Microbiology,2015,207:1-7.
[80] WANG L,PENG R,LIU X,et al.Nitrite-enhanced copper-based Fenton reactions for biofilm removal[J].Chemical Communications (Camb),2021,57(45):5514-5517.
[81] 闫冠韫.天然药物向化学药物转化的历程[D].哈尔滨：黑龙江中医药大学,2013. YAN G Y.The development history of natural medicine transform to chemical medicine[D].Harbin:Heilongjiang University of Chinese Medicine,2013.(in Chinese)
[82] 许晶.蒲公英水提物对猪链球菌生物被膜体外干预作用[D].哈尔滨：东北农业大学,2015. XU J.The dandelion water extract on biological membrane in vitro by intervention effect of Streptococcus suis[D].Harbin:Northeast Agricultural University,2015.(in Chinese)
[83] 王金玉,姜晓文,王娜,等.穿心莲内酯影响猪链球菌生物被膜形成[J].畜牧兽医学报,2018,49(3):629-636. WANG J Y,JIANG X W,WANG N,et al.Effect of andrographolide on the biofilm formation of Streptococcus suis[J].Acta Veterinaria et Zootechnica Sinica,2018,49(3):629-636.(in Chinese)
[84] WANG S,WANG C,GAO L,et al.Rutin inhibits Streptococcus suis biofilm formation by affecting CPS biosynthesis[J].Frontiers in Pharmacology,2017,8:379.
[85] 刘冰,韩强,盛尊来,等.黄连水提物盐酸小檗碱及黄连碱对猪链球菌生物被膜的体外干预作用[J].中国兽医杂志,2015,51(4):16-19. LIU B,HAN Q,SHENG Z L,et al.Intervention effects of water extract,berberine hydrochloride and coptisine from Rhizoma coptidis against Streptococcus suis biofilm in vitro[J].Chinese Journal of Veterinary Medicine,2015,51(4):16-19.(in Chinese)
[86] 高晓慧,梁馨元,何舒平,等.黄连解毒汤联合氟康唑对白色念珠菌生物膜的体外影响的研究[J].广东化工,2022,49(2):29-30. GAO X H,LIANG X Y,HE S P,et al.Effect of Huanglian Jiedu decoction combined with fluconazole on Candida albicans biofilm in vitro[J].Guangdong Chemical Industry,2022,49(2):29-30.(in Chinese)
[87] 刘力娟,马立艳,孙伟,等.盐酸小檗碱对耐碳青霉烯类鲍曼不动杆菌生物膜的作用[J].临床检验杂志,2022,40(8):589-594. LIU L J,MA L Y,SUN W,et al.Effect of berberine hydrochloride on carbapenem-resistant Acinetobacter baumannii biofilm[J].Chinese Journal of Clinical Laboratory Science,2022,40(8):589-594.(in Chinese).