禽致病性大肠杆菌黏附素疫苗研究进展

doi:10.16431/j.cnki.1671-7236.2023.12.027

摘要/Abstract

摘要： 禽致病性大肠杆菌(avian pathogenic Escherichia coli,APEC)是导致不同日龄禽类局部和全身感染的重要病原菌,也是人肠外致病性大肠杆菌(extraintestinal pathogenic E.coli,ExPEC)毒力基因的重要贮存库或来源。随着APEC耐药菌株的日益增多,迫切需要开辟防控APEC感染的有效途径,其中阻止细菌感染的初始阶段便是防控感染的最有效措施之一。黏附素除介导细菌与宿主组织结合外,也是成功建立初始感染的第一步。因此,利用黏附素作为靶标制备疫苗预防APEC感染将是一种极有前途的策略。笔者重点介绍了菌毛黏附素、非菌毛黏附素和非典型黏附素等的结构与功能,以及有望成为APEC候选疫苗的黏附素的应用潜力和最新研究进展,如1型菌毛、P菌毛、普通菌毛、Yqi菌毛、Stg菌毛、Curli菌毛、温度敏感血凝素(Tsh)、AatA、FdeC、YeeJ、鞭毛蛋白、脂多糖(LPS)和外膜蛋白A等。黏附素疫苗一旦开发成功,将有望成为一种防控APEC感染的有力手段。

关键词: 禽致病性大肠杆菌; 黏附素; 黏附素疫苗

Abstract: Avian pathogenic Escherichia coli (APEC) is an important pathogen that causes local and systemic infections in birds of different ages,and is also an important reservoir or source of virulence genes for human extraintestinal pathogenic Escherichia coli(ExPEC).With the increasing number of APEC-resistant strains,there is an urgent need to develop effective ways to prevent and control APEC infection,and preventing bacterial infection at the initial stage is one of the most effective measures to combat infection.In addition to mediating bacterial binding to host tissues,adhesins are the first step in the successful establishment of an initial infection.Therefore,using adhesin as a target to prepare a vaccine to prevent APEC infection will be a very promising strategy.The authors focus on the structure and functions of various adhesins,including fimbrial adhesins,afimbrial adhesins (Afa) and atypical adhesins.It also discusses their potential as candidate vaccine adhesins for APEC,some of the adhesins mentioned include type 1 fimbriae,P fimbriae,common fimbriae,Yqi fimbriae,Stg fimbriae,curli fimbriae,temperature-sensitive hemagglutinin (Tsh),AatA,FdeC,YeeJ,flagellin,lipopolysaccharide (LPS), outer membrane protein A,etc.Once successfully developed,the adhesin-based vaccines is expected to become a powerful means of preventing and controlling APEC infection.

Key words: avian pathogenic Escherichia coli; adhesin; adhesin-based vaccines

中图分类号:

S852.61

马兴树, 宋金祥, 石虎. 禽致病性大肠杆菌黏附素疫苗研究进展[J]. 中国畜牧兽医, 2023, 50(12): 5056-5066.

MA Xingshu, SONG Jinxiang, SHI Hu. Current Progress on Adhesin-based Vaccines for Avian Pathogenic Escherichia coli[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(12): 5056-5066.

参考文献

[1] RAYNES J M,YOUNG P G,PROFT T,et al.Protein adhesins as vaccine antigens for group A Streptococcus[J].Pathogens and Disease,2018,76(2).Doi:10.1093/femspd/fty016.
[2] PATEL S,MATHIVANAN N,GOYAL A.Bacterial adhesins,the pathogenic weapons to trick host defense arsenal[J]. Biomedicine & Pharmacotherapy,2017,93:763-771.
[3] COZENS D,READ R C.Anti-adhesion methods as novel therapeutics for bacterial infections[J].Expert Review of Anti-Infective Therapy,2012,10(12):1457-1468.
[4] 马兴树,强慧勤,杨锴.禽致病性大肠杆菌实验感染模型研究进展[J].中国畜牧兽医,2020,47(12):4103-4118. MA X S,QIANG H Q,YANG K.Advances on the experimental infectious models of avian pathogenic Escherichia coli[J].China Animal Husbandry & Veterinary Medicine,2020,47(12):4103-4118.(in Chinese)
[5] SWAYNE D E,BOULIANNE M,LOGUE C M,et al.Diseases of Poultry[M].14th ed.Hoboken:Wiley Blackwell,2020.
[6] MEENA P R,YADAV P,HEMLATA H,et al.Poultry origin extraintestinal Escherichia coli strains carrying the traits associated with urinary tract infection,sepsis,meningitis and avian colibacillosis in India[J].Journal of Applied Microbiology,2021,130(6):2087-2101.
[7] ZHUGE X,ZHOU Z,JIANG M,et al.Chicken-source Escherichia coli within phylogroup F shares virulence genotypes and is closely related to extraintestinal pathogenic E.coli causing human infections[J].Transboundary and Emerging Diseases,2021,68(2):880-895.
[8] MARKLAND S M,LESTRANGE K J,SHARMA M,et al.Old friends in new places:Exploring the role of extraintestinal E.coli in intestinal disease and foodborne illness[J].Zoonoses and Public Health,2015,62(7):491-496.
[9] ALEKSANDROWICZ A,KHAN M M,SIDORCZUK K,et al.Whatever makes them stick-Adhesins of avian pathogenic Escherichia coli[J].Veterinary Microbiology,2021,257:109095.
[10] SORA V M,MERONI G,MARTINO P A,et al.Extraintestinal pathogenic Escherichia coli:Virulence factors and antibiotic resistance[J].Pathogens,2021,10(11):1355.
[11] NUCCIO S P,BAUMLER A J.Evolution of the chaperone/usher assembly pathway:Fimbrial classification goes Greek[J].Microbiology and Molecular Biology Reviews,2007,71(4):551-575.
[12] THANASSI D G,NUCCIO S P,SHUKIN SO S,et al.Fimbriae:Classification and biochemistry[J].EcoSal Plus,2007,2(2).Doi:10.1128/ecosalplus.2.4.2.1.
[13] HABOURIA H,BESSAIAH H,POKHAREL P,et al.A newly identified group of P-like (PL) fimbria genes from extraintestinal pathogenic Escherichia coli (ExPEC) encode distinct adhesin subunits and mediate adherence to host cells[J].Applied and Environmental Microbiology,2022,88(13):e01421-21.
[14] HOSPENTHAL M K,COSTA T R D,WAKSMAN G.A comprehensive guide to pilus biogenesis in Gram-negative bacteria[J].Nature Reviews Microbiology,2017,15(6):365-379.
[15] BERNE C,DUCRET A,HARDY G G,et al.Adhesins involved in attachment to abiotic surfaces by Gram-negative bacteria[J].Microbial Biofilms,2015:163-199.
[16] VO J L,MARTÍNEZ ORTIZ G C,SUBEDI P,et al.Autotransporter adhesins in Escherichia coli pathogenesis[J].Proteomics,2017,17(23-24):1600431.
[17] CLARKE K R,HOR L,PILAPITIYA A,et al.Phylogenetic classification and functional review of autotransporters[J].Frontiers in Immunology,2022,13:921272.
[18] COPPENS F,CASTALDO G,DEBRAEKELEER A,et al.Hop-family Helicobacter outer membrane adhesins form a novel class of type 5-like secretion proteins with an interrupted β-barrel domain[J].Molecular Microbiology,2018,110(1):33-46.
[19] DE PACE F,NAKAZATO G,PACHECO A,et al.The type Ⅵ secretion system plays a role in type 1 fimbria expression and pathogenesis of an avian pathogenic Escherichia coli strain[J].Infection and Immunity,2010,78(12):4990-4998.
[20] DE PACE F,DE PAIVA J B,NAKAZATO G,et al.Characterization of IcmF of the type Ⅵ secretion system in an avian pathogenic Escherichia coli (APEC) strain[J].Microbiology,2011,157(Pt10):2954.
[21] MA J,BAO Y,SUN M,et al.Two functional type Ⅵ secretion systems in avian pathogenic Escherichia coli are involved in different pathogenic pathways[J].Infection and Immunity,2014,82(9):3867-3879.
[22] KLEMM P,SCHEMBRI M A.Bacterial adhesins:Function and structure[J].International Journal of Medical Microbiology,2000,290(1):27-35.
[23] ALBER A,STEVENS M P,VERVELDE L.The bird’s immune response to avian pathogenic Escherichia coli[J].Avian Pathology,2021,50(5):382-391.
[24] IRVIN R T,BAUTISTA D L.Hope for the post-antibiotic era?[J].Nature Biotechnology,1999,17(1):20.
[25] NAVEH M W,ZUSMAN T,SKUTELSKY E,et al.Adherence pili in avian strains of Escherichia coli:Effect on pathogenicity[J].Avian Diseases 1984,28(3):651-661.
[26] EWERS C,JANBEN T,KIEBLING S,et al.Molecular epidemiology of avian pathogenic Escherichia coli (APEC) isolated from colisepticemia in poultry[J].Veterinary Microbiology,2004,104(1-2):91-101.
[27] VANDEMAELE F J,HENSEN S M,GODDEERIS B M.Conservation of deduced amino acid sequence of FimH among Escherichia coli of bovine,porcine and avian disease origin[J].Veterinary Microbiology,2004,101(2):147-152.
[28] LANGERMANN S,PALASZYNSKI S,BARNHART M,et al.Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination[J]. Science,1997,276(5312):607-611.
[29] VANDEMAELE F,VERVERKEN C,BLEYEN N,et al.Immunization with the binding domain of FimH,the adhesin of type1 fimbriae,does not protect chickens against avian pathogenic Escherichia coli[J].Avian Pathology,2005,34(3):264-272.
[30] KARIYAWASAM S,WILKIE B N,GYLES C L.Resistance of broiler chickens to Escherichia coli respiratory tract infection induced by passively transferred egg-yolk antibodies[J].Veterinary Microbiology,2004,98(3-4):273-284.
[31] TCHESNOKOVA V,APRIKIAN P,KISIELA D,et al.Type 1 fimbrial adhesin FimH elicits an immune response that enhances cell adhesion of Escherichia coli[J].Infection and Immunity,2011,79(10):3895-3904.
[32] SOKURENKO E V,TCHESNOKOVA V,INTERLANDI G,et al.Neutralizing antibodies against allosteric proteins:Insights from a bacterial adhesin[J].Journal of Molecular Biology,2022,434(17):167681.
[33] LUNA-PINEDA V M,REYES-GRAJEDA J P,CRUZ-CÓRDOVA A,et al.Dimeric and trimeric fusion proteins generated with fimbrial adhesins of uropathogenic Escherichia coli[J].Frontiers in Cellular and Infection Microbiology,2016,6:135.
[34] THOMAS W E,CARLUCCI L,YAKOVENKO O,et al.Recombinant FimH adhesin demonstrates how the allosteric catch bond mechanism can support fast and strong bacterial attachment in the absence of shear[J].Journal of Molecular Biology,2022,434(17):167681.
[35] KARIYAWASAM S,NOLAN L K.Pap mutant of avian pathogenic Escherichia coli O1,an O1∶K1∶H7 strain,is attenuated in vivo[J].Avian Diseases,2009,53(2):255-260.
[36] VANDEMAELE F,BLEYEN N,ABUABOUD O,et al.Immunization with the biologically active lectin domain of PapGⅡinduces strong adhesion-inhibiting antibody responses but not protection against avian pathogenic Escherichia coli[J].Avian Pathology,2006,35(3):238-249.
[37] RENDÓN M A,SALDAÑA Z,ERDEM A L,et al.Commensal and pathogenic Escherichia coli use a common pilus adherence factor for epithelial cell colonization[J].Proceedings of the National Academy of Sciences of the United States of America,2007,104(25):10637-10642.
[38] STACY A K,MITCHELL N M,MADDUX J T,et al.Evaluation of the prevalence and production of Escherichia coli common pilus among avian pathogenic E.coli and its role in virulence[J].PLoS One,2014,9(1):e86565.
[39] MADDUX J T,STROMBERG Z R,CURTISS III R,et al.Evaluation of recombinant attenuated Salmonella vaccine strains for broad protection against extraintestinal pathogenic Escherichia coli[J].Frontiers in Immunology,2017,8:1280.
[40] ANTÃO E M,EWERS C,GVRLEBECK D,et al.Signature-tagged mutagenesis in a chicken infection model leads to the identification of a novel avian pathogenic Escherichia coli fimbrial adhesin[J].PLoS One,2009,4(11):e7796.
[41] SARAH B,ESTHER M A,RICHTER C,et al.Novel functions and binding partners of the ExPEC adhesin Ⅰ[A].5th Congress of European Microbiologists[C].2013.
[42] LYMBEROPOULOS M H,HOULE S,DAIGLE F,et al.Characterization of Stg fimbriae from an avian pathogenic Escherichia coli O78∶K80 strain and assessment of their contribution to colonization of the chicken respiratory tract[J].Journal of Bacteriology,2006,188(18):6449-6459.
[43] OLSEN A,JONSSON A,NORMARK S.Fibronectin binding mediated by a novel class of surface organelles on Escherichia coli[J].Nature,1989,338(6217):652-655.
[44] YAN Z,YIN M,CHEN J,et al.Assembly and substrate recognition of curli biogenesis system[J].Nature Communications,2020,11(1):241.
[45] RAPSINSKI G J,WYNOSKY-DOLFI M A,OPPONG G O,et al.Toll-like receptor 2 and NLRP3 cooperate to recognize a functional bacterial amyloid,curli[J].Infection and Immunity,2015,83(2):693-701.
[46] GOPHNA U,OELSCHLAEGER T A,HACKER J,et al.Role of fibronectin in curli-mediated internalization[J].FEMS Microbiology Letters,2002,212(1):55-58.
[47] LA RAGIONE R M,COOLEY W A,WOODWARD M J.The role of fimbriae and flagella in the adherence of avian strains of Escherichia coli O78∶K80 to tissue culture cells and tracheal and gut explants[J].Journal of Medical Microbiology,2000,49(4):327-338.
[48] KARAN S,CHOUDHURY D,DIXIT A.Immunogenic characterization and protective efficacy of recombinant CsgA,major subunit of curli fibers,against Vibrio parahaemolyticus[J].Applied Microbiology and Biotechnology,2021,105(2):599-616.
[49] MULVEY M,KLUMPP D J,STAPLETON A.Urinary Tract Infections:Molecular Pathogenesis and Clinical Management[M].2nd ed.Wiley,2017.
[50] CELIK N,WEBB C T,LEYTON D L,et al.A bioinformatic strategy for the detection,classification and analysis of bacterial autotransporters[J].PLoS One,2012,7(8):e43245.
[51] VAN ULSEN P,UR RAHMAN S,JONG W S P,et al.Type V secretion:From biogenesis to biotechnology[J].Biochimica et Biophysica Acta,2014,1843(8):1592-1611.
[52] NICOLAY T,VANDERLEYDEN J,SPAEPEN S.Autotransporter-based cell surface display in Gram-negative bacteria[J].Critical Reviews in Microbiology,2015,41(1):109-123.
[53] PROVENCE D L,CURTISS 3RD R.Isolation and characterization of a gene involved in hemagglutination by an avian pathogenic Escherichia coli strain[J].Infection and Immunity,1994,62(4):1369-1380.
[54] KOSTAKIOTI M,STATHOPOULOS C.Functional analysis of the Tsh autotransporter from an avian pathogenic Escherichia coli strain[J].Infection and Immunity,2004,72(10):5548-5554.
[55] DOZOIS C M,DHO-MOULIN M,BRÉE A,et al.Relationship between the Tsh autotransporter and pathogenicity of avian Escherichia coli and localization and analysis of the Tsh genetic region[J].Infection and Immunity,2000,68(7):4145-4154.
[56] DELICATO E R,DE BRITO B G,KONOPATZKI A P,et al.Occurrence of the temperature-sensitive hemagglutinin among avian Escherichia coli[J]. Avian Diseases,2002,46(3):713-716.
[57] KOBAYASHI R K T,GAZIRI L C J,VIDOTTO M C.Functional activities of the Tsh protein from avian pathogenic Escherichia coli (APEC) strains[J].Journal of Veterinary Science,2010,11(4):315-319.
[58] 张鑫,马兴树,牛志勇,等.发明专利号ZL.2012 8 0061061.7,预防禽类大肠杆菌病的广谱菌苗的制备方法[P].2012. ZHANG X,MA X S,NIU Z Y,et al.Invention Patent Number ZL.2012 8 0061061.7,preparation method of broad-spectrum vaccine for preventing avian colibacillosis[P].2012.(in Chinese)
[59] DAI J,WANG S,GUERLEBECK D,et al.Suppression subtractive hybridization identifies an autotransporter adhesin gene of E.coli IMT5155 specifically associated with avian pathogenic Escherichia coli (APEC)[J].BMC Microbiology,2010,10(1):236-252.
[60] LI G,FENG Y,KARIYAWASAM S,et al.AatA is a novel autotransporter and virulence factor of avian pathogenic Escherichia coli[J].Infection and Immunity,2010,78(3):898-906.
[61] ZHUGE X,WANG S,FAN H,et al.Characterization and functional analysis of AatB,a novel autotransporter adhesin and virulence factor of avian pathogenic Escherichia coli[J].Infection and Immunity,2013,81(7):2437-2447.
[62] NESTA B,SPRAGGON G,ALTERI C,et al.FdeC,a novel broadly conserved Escherichia coli adhesin eliciting protection against urinary tract infections[J].mBio,2012,3(2):e00010-12.
[63] EASTON D M,ALLSOPP L P,PHAN M D,et al.The intimin-like protein FdeC is regulated by H-NS and temperature in enterohemorrhagic Escherichia coli[J].Applied and Environmental Microbiology,2014,80(23):7337-7347.
[64] MARTINEZ G M,GOH K G K,RACKAITYTE E,et al.YeeJ is an inverse autotransporter from Escherichia coli that binds to peptidoglycan and promotes biofilm formation[J]. Scientific Reports,2017,7(1):11326.
[65] LATASA C,ROUX A,TOLEDO A,et al.BapA,a large secreted protein required for biofilm formation and host colonization of Salmonella enterica serovar Enteritidis[J].Molecular Microbiology,2005,58(5):1322-1339.
[66] KRACHLER A M,ORTH K.Targeting the bacteria-host interface:Strategies in anti-adhesion therapy[J].Virulence,2013,4(4):284-294.
[67] ZHOU X,GIRÓN J A,TORRES A G,et al.Flagellin of enteropathogenic Escherichia coli stimulates interleukin-8 production in T84 cells[J].Infection and Immunity,2003,71(4):2120-2129.
[68] DE PAIVA J B,DA SILVA L P M,CASAS M R T,et al. In vivo influence of in vitro up-regulated genes in the virulence of an APEC strain associated with swollen head syndrome[J].Avian Pathology,2016,45(1):94-105.
[69] HAJAM I A,DAR P A,SHAHNAWAZ I,et al.Bacterial flagellin—A potent immunomodulatory agent[J].Experimental & Molecular Medicine,2017,49(9):e373.
[70] CUI B,LIU X,FANG Y,et al.Flagellin as a vaccine adjuvant[J].Expert Review of Vaccines,2018,17(4):335-349.
[71] KHIM K,BANG Y J,PUTH S,et al.Deimmunization of flagellin for repeated administration as a vaccine adjuvant[J].NPJ Vaccines,2021,6:116.
[72] CRIŞAN T O,NETEA M G,JOOSTEN L A.Innate immune memory:Implications for host responses to damage-associated molecular patterns[J].European Journal of Immunology.2016,46,817-828.
[73] BRAVO D,SILVA C,CARTER J A,et al.Growth-phase regulation of lipopolysaccharide O-antigen chain length influences serum resistance in serovars of Salmonella[J].Journal of Medical Microbiology,2008,57(8):938-946.
[74] ZUO J,TU C,WANG Y,et al.The role of the wzy gene in lipopolysaccharide biosynthesis and pathogenesis of avian pathogenic Escherichia coli[J].Microbial Pathogenesis,2019,127:296-303.
[75] HUJA S,OREN Y,TROST E,et al.Genomic avenue to avian colisepticemia[J]. mBio,2015,6(1):e01681-14.
[76] WAGENLEHNER F M E,NABER K G.A step further in a vaccine for Escherichia coli[J].The Lancet Infectious Diseases,2019,19(6):565-567.
[77] BENNETT G E,MCINTOSH T J,BARCLAY G R,et al.Preparation and preclinical evaluation of a novel liposomal complete-core lipopolysaccharide vaccine[J].Infection and Immunity,2000,68(11):6202-6208.
[78] GUAN Q,BHOWMICK B,UPADHYAY A,et al.Structure and functions of bacterial outer membrane protein A,a potential therapeutic target for bacterial infection[J].Current Topics in Medicinal Chemistry,2021,21(13):1129-1138.
[79] NIELSEN D W,RICKER N,BARBIERI N L,et al.Outer membrane protein A (OmpA) of extraintestinal pathogenic Escherichia coli[J].BMC Research Notes,2020,13(51):1-7.
[80] GUAN Q,WANG X,WANG X,et al.Recombinant outer membrane protein A induces a protective immune response against Escherichia coli infection in mice[J].Applied Microbiology and Biotechnology,2015,99:5451-5460.
[81] GU H,LIAO Y,ZHANG J,et al.Rational design and evaluation of an artificial Escherichia coli K1 protein vaccine candidate based on the structure of OmpA[J].Frontiers in Cellular and Infection Microbiology,2018,8:172.
[82] LEI L,YANG F,ZOU J,et al.DNA vaccine encoding OmpA and Pal from Acinetobacter baumannii efficiently protects mice against pulmonary infection[J].Molecular Biology Reports,2019,46:5397-5408.