多杀性巴氏杆菌的摄铁机制研究进展

doi:10.11843/j.issn.0366-6964.2024.11.007

摘要/Abstract

摘要：

多杀性巴氏杆菌可广泛感染多种动物，引起出血性败血症或传染性肺炎。铁是多杀性巴氏杆菌感染宿主过程中生长、定植和增殖必不可少的营养物质，竞争宿主铁离子是该病原体感染致病的关键环节。近年来，多杀性巴氏杆菌的摄铁系统及其发生与调控机制方面的研究取得了一系列重要进展。本文系统阐述了多杀性巴氏杆菌的转铁蛋白受体摄铁机制、血红素受体摄铁机制、铁载体摄铁机制及其摄铁系统的表达与调控机制，以期为多杀性巴氏杆菌摄铁系统的分子致病机理研究提供系统的理论知识，为多杀性巴氏杆菌分子靶标药物及亚单位疫苗的研发提供新思路。

关键词: 多杀性巴氏杆菌, 摄铁机制, 铁载体, ExbB-ExbD-TonB, Fur

Abstract:

Pasteurella multocida (P. multocida) can infect a wide range of animals, causing hemorrhagic septicemia or infectious pneumonia. Iron is an essential nutrient for growth, colonization, and proliferation of P. multocida during infection of the host, and competition for iron ions in the host is a critical link in the pathogenesis of this pathogen. In recent years, a series of significant research advances have progressed in the iron uptake system of P. multocida, as well as its occurrence and regulatory mechanisms. The mechanisms of iron uptake by transferrin, heme receptors and siderophore, and the mechanism of expression and regulation of the P. multocida iron uptake system are all described in this paper. Aiming to provide systematic theoretical knowledge for the study of the molecular pathogenesis of the P. multocida iron uptake system and to spark new ideas for the investigation and development of molecular target drugs and subunit vaccines of P. multocida.

Key words: Pasteurella multocida, iron uptake mechanism, siderophore, ExbB-ExbD-TonB, Fur

中图分类号:

沈香香, 关丽君, 张俊峰, 薛云, 司丽芳, 赵战勤. 多杀性巴氏杆菌的摄铁机制研究进展[J]. 畜牧兽医学报, 2024, 55(11): 4852-4862.

Xiangxiang SHEN, Lijun GUAN, Junfeng ZHANG, Yun XUE, Lifang SI, Zhanqin ZHAO. Research Progress on Iron Uptake Mechanism of Pasteurella multocida[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(11): 4852-4862.

图/表 4

参考文献 97

1	BETHEA,WIELERL H,SELBITZH J,et al.Genetic diversity of porcine Pasteurella multocida strains from the respiratory tract of healthy and diseased swine[J].Vet Microbiol,2009,139(1-2):97-105. doi: 10.1016/j.vetmic.2009.04.027
2	CARTERG R.Studies on Pasteurella multocida.I.A hemagglutination test for the identification of serological types[J].Am J Vet Res,1955,16(60):481-484.
3	HEDDLESTONK L,GALLAGHERJ E,REBERSP A.Fowl cholera: gel diffusion precipitin test for serotyping Pasteurella multocida from avian species[J].Avian Dis,1972,16(4):925-936. doi: 10.2307/1588773
4	HARPERM,BOYCEJ D,ADLERB.Pasteurella multocida pathogenesis: 125 years after Pasteur[J].FEMS Microbiol Lett,2006,265(1):1-10. doi: 10.1111/j.1574-6968.2006.00442.x
5	FLOSSMANNK D,MÜLLERG,HEILMANNP,et al.Effect of iron on Pasteurella multocida[J].Zentralbl Bakteriol Mikrobiol Hyg A,1984,258(1):80-93.
6	VARSHNEYR,VARSHNEYR,CHATURVEDIV K,et al.Development of novel iron-regulated Pasteurella multocida B: 2 bacterin and refinement of vaccine quality in terms of minimum variation in particle size and distribution vis-a-vis critical level of iron in media[J].Microb Pathog,2020,147,104375. doi: 10.1016/j.micpath.2020.104375
7	JATUPONWIPHATT,CHUMNANPUENP,OTHMANS,et al.Iron-associated protein interaction networks reveal the key functional modules related to survival and virulence of Pasteurella multocida[J].Microb Pathog,2019,127,257-266. doi: 10.1016/j.micpath.2018.12.013
8	POGOUTSEA K,MORAEST F.Iron acquisition through the bacterial transferrin receptor[J].Crit Rev Biochem Mol Biol,2017,52(3):314-326. doi: 10.1080/10409238.2017.1293606
9	JAKUBOVICSN S,JENKINSONH F.Out of the iron age: new insights into the critical role of manganese homeostasis in bacteria[J].Microbiology,2001,147(Pt 7):1709-1718.
10	HEF,QINX B,XUN,et al.Pasteurella multocida Pm0442 affects virulence gene expression and targets TLR2 to induce inflammatory responses[J].Front Microbiol,2020,11,e1972. doi: 10.3389/fmicb.2020.01972
11	JACQUESM,BÉLANGERM,DIARRAM S,et al.Modulation of Pasteurella multocida capsular polysaccharide during growth under iron-restricted conditions and in vivo[J].Microbiology,1994,140(Pt 2):263-270.
12	VARSHNEYR,CHATURVEDIV,AGRAWALA,et al.Growth kinetics of Pasteurella multocida B: 2 in iron controlled conditions in broth media[J].Int J Livest Res,2018,8(5):205-212.
13	FLOSSMANNK D,ROSNERH,GRÜNKEU,et al.Modification of virulence and immunogenicity of Pasteurella multocida by iron in vitro[J].Z Allg Mikrobiol,1984,24(4):231-7.
14	GKOUVATSOSK,PAPANIKOLAOUG,PANTOPOULOSK.Regulation of iron transport and the role of transferrin[J].Biochim Biophys Acta Gen Subj,2012,1820(3):188-202. doi: 10.1016/j.bbagen.2011.10.013
15	PAUSTIANM L,MAYB J,KAPURV.Pasteurella multocida gene expression in response to iron limitation[J].Infect Immun,2001,69(6):4109-4115. doi: 10.1128/IAI.69.6.4109-4115.2001
16	PALMERL D,SKAARE P.Transition metals and virulence in bacteria[J].Annu Rev Genet,2016,50,67-91. doi: 10.1146/annurev-genet-120215-035146
17	BEINERTH,HOLMR H,MÜNCKE.Iron-sulfur clusters: nature's modular, multipurpose structures[J].Science,1997,277(5326):653-659. doi: 10.1126/science.277.5326.653
18	THAYERM M,AHERNH,XINGD,et al.Novel DNA binding motifs in the DNA repair enzyme endonuclease Ⅲ crystal structure[J].EMBO J,1995,14(16):4108-4120. doi: 10.1002/j.1460-2075.1995.tb00083.x
19	GRANDONIJ A,SWITZERR L,MAKAROFFC A,et al.Evidence that the iron-sulfur cluster of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase determines stability of the enzyme to degradation in vivo[J].J Biol Chem,1989,264(11):6058-6064. doi: 10.1016/S0021-9258(18)83312-9
20	BEHRINGERM,PLÖTZKYL,BAABED,et al.RirA of Dinoroseobacter shibae senses iron via a[3Fe-4S]¹⁺ cluster co-ordinated by three cysteine residues[J].Biochem J,2020,477(1):191-212. doi: 10.1042/BCJ20180734
21	GAUDUP,WEISSB.SoxR, a[2Fe-2S] transcription factor, is active only in its oxidized form[J].Proc Natl Acad Sci U S A,1996,93(19):10094-10098. doi: 10.1073/pnas.93.19.10094
22	STOJILJKOVICI,PERKINS-BALDINGD.Processing of heme and heme-containing proteins by bacteria[J].DNA Cell Biol,2002,21(4):281-295. doi: 10.1089/104454902753759708
23	JORDANR M M.The nutrition of Pasteurella septica.I.The action of haematin[J].Br J Exp Pathol,1952,33(1):27-35.
24	潘梅. 大肠杆菌血红素合成调节及其对血红素过氧化物酶的影响[D]. 无锡: 江南大学, 2020.
	PAN M. Regulation of heme synthesis and its effect on heme peroxidase in Escherichia coli[D]. Wuxi: Jiangnan University, 2020. (in Chinese)
25	HAMMERN D,RENIEREM L,CASSATJ E,et al.Two heme-dependent terminal oxidases power Staphylococcus aureus organ-specific colonization of the vertebrate host[J].mBio,2013,4(4):e00241-13.
26	刘琪. 大肠杆菌过氧化物酶EfeB的生理功能及其对血红素代谢的影响[D]. 无锡: 江南大学, 2022.
	LIU Q. Physiological function of Escherichia coli peroxidase EfeB and its effect on heme metabolism[D]. Wuxi: Jiangnan University, 2022. (in Chinese)
27	SHIX J,ZHAOG Y,LIH,et al.Hydroxytryptophan biosynthesis by a family of heme-dependent enzymes in bacteria[J].Nat Chem Biol,2023,19(11):1415-1422. doi: 10.1038/s41589-023-01416-0
28	MIETHKEM,MARAHIELM A.Siderophore-based iron acquisition and pathogen control[J].Microbiol Mol Biol Rev,2007,71(3):413-451. doi: 10.1128/MMBR.00012-07
29	RATLEDGEC,DOVERL G.Iron metabolism in pathogenic bacteria[J].Annu Rev Microbiol,2000,54,881-941. doi: 10.1146/annurev.micro.54.1.881
30	PENGZ,WANGX R,ZHOUR,et al.Pasteurella multocida: genotypes and genomics[J].Microbiol Mol Biol Rev,2019,83(4):e00014-19.
31	SUNY,WANGX H,GONGQ W,et al.Extraintestinal pathogenic Escherichia coli utilizes surface-located elongation factor g to acquire iron from holo-transferrin[J].Microbiol Spectr,2022,10(2):e0166221. doi: 10.1128/spectrum.01662-21
32	SHIVACHANDRAS B,KUMARA A,AMARANATHJ,et al.Cloning and characterization of tbpA gene encoding transferrin-binding protein (TbpA) from Pasteurella multocida serogroup B: 2 (strain P₅₂)[J].Vet Res Commun,2005,29(6):537-542. doi: 10.1007/s11259-005-2495-6
33	CORNELISSENC N,HOLLANDERA.TonB-dependent transporters expressed by Neisseria gonorrhoeae[J].Front Microbiol,2011,2,117.
34	SAMANTARRAID,LAKSHMAN SAGARA,GUDLAR,et al.TonB-dependent transporters in Sphingomonads: unraveling their distribution and function in environmental adaptation[J].Microorganisms,2020,8(3):359. doi: 10.3390/microorganisms8030359
35	VEKENJ W,OUDEGAB,LUIRINKJ,et al.Binding of bovine transferrin by Pasteurella multocida serotype B: 2, 5, a strain which causes haemorrhagic septicaemia in buffalo and cattle[J].FEMS Microbiol Lett,1994,115(2-3):253-257. doi: 10.1111/j.1574-6968.1994.tb06647.x
36	BOSHUIZENM,VAN DER PLOEGK,VON BONSDORFFL,et al.Therapeutic use of transferrin to modulate anemia and conditions of iron toxicity[J].Blood Rev,2017,31(6):400-405. doi: 10.1016/j.blre.2017.07.005
37	MOECKG S,COULTONJ W.TonB-dependent iron acquisition: mechanisms of siderophore-mediated active transport[J].Mol Microbiol,1998,28(4):675-681. doi: 10.1046/j.1365-2958.1998.00817.x
38	TUCKMANM,OSBURNEM S.In vivo inhibition of TonB-dependent processes by a TonB box consensus pentapeptide[J].J Bacteriol,1992,174(1):320-323. doi: 10.1128/jb.174.1.320-323.1992
39	SILALEA,VAN DEN BERGB.TonB-dependent transport across the bacterial outer membrane[J].Annu Rev Microbiol,2023,77,67-88. doi: 10.1146/annurev-micro-032421-111116
40	KLEBBAP E.ROSET Model of TonB action in gram-negative bacterial iron acquisition[J].J Bacteriol,2016,198(7):1013-1021. doi: 10.1128/JB.00823-15
41	LARSENR A,DECKERTG E,KASTEADK A,et al.His₂₀ provides the sole functionally significant side chain in the essential TonB transmembrane domain[J].J Bacteriol,2007,189(7):2825-2833. doi: 10.1128/JB.01925-06
42	BELZERC A,TABATABAIL B,FRANKG H.Purification and characterization of the Pasteurella haemolytica 35 kilodalton periplasmic iron-regulated protein[J].Prep Biochem Biotechnol,2000,30(4):343-355. doi: 10.1080/10826060008544973
43	CHANC,NGD,FRASERM E,et al.Structural and functional insights into iron acquisition from lactoferrin and transferrin in Gram-negative bacterial pathogens[J].Biometals,2023,36(3):683-702. doi: 10.1007/s10534-022-00466-6
44	SHOULDICES R,DOUGAND R,WILLIAMSP A,et al.Crystal structure of Pasteurella haemolytica ferric ion-binding protein A reveals a novel class of bacterial iron-binding proteins[J].J Biol Chem,2003,278(42):41093-41098. doi: 10.1074/jbc.M306821200
45	ADHIKARIP,BERISHS A,NOWALKA J,et al.The fbpABC locus of Neisseria gonorrhoeae functions in the periplasm-to-cytosol transport of iron[J].J Bacteriol,1996,178(7):2145-2149. doi: 10.1128/jb.178.7.2145-2149.1996
46	李红敏,龙章彪,韩冰.铁稳态的维持及铁代谢相关疾病[J].中华血液学杂志,2018,39(9):790-792.
	LIH M,LONGZ B,HANB.Iron homeostasis and iron-related disorders[J].Chinese Journal of Hematology,2018,39(9):790-792.
47	TOLOSANOE,FAGOONEES,MORELLON,et al.Heme scavenging and the other facets of hemopexin[J].Antioxid Redox Signal,2010,12(2):305-320. doi: 10.1089/ars.2009.2787
48	PAUSTIANM L,MAYB J,CAOD W,et al.Transcriptional response of Pasteurella multocida to defined iron sources[J].J Bacteriol,2002,184(23):6714-6720. doi: 10.1128/JB.184.23.6714-6720.2002
49	GELLD A.Structure and function of haemoglobins[J].Blood Cells Mol Dis,2018,70,13-42. doi: 10.1016/j.bcmd.2017.10.006
50	程兴军,刘马峰,程安春.革兰氏阴性菌血红素转运系统结构及功能特点[J].中国生物化学与分子生物学报,2014,30(9):848-855.
	CHENGX J,LIUM F,CHENGA C.Structural and functional properties of the Heme acquisition system in gram-negative bacteria[J].Chinese Journal of Biochemistry and Molecular Biology,2014,30(9):848-855.
51	PRASANNAVADHANAA,KUMARS,THOMASP,et al.Outer membrane proteome analysis of Indian strain of Pasteurella multocida serotype B: 2 by MALDI-TOF/MS analysis[J].Sci World J,2014,2014,617034.
52	SRIKUMARR,MIKAELL G,PAWELEKP D,et al.Molecular cloning of haemoglobin-binding protein HgbA in the outer membrane of Actinobacillus pleuropneumoniae[J].Microbiology,2004,150(Pt 6):1723-1734.
53	QASEM-ABDULLAHH,PERACHM,LIVNAT-LEVANONN,et al.ATP binding and hydrolysis disrupt the high-affinity interaction between the heme ABC transporter HmuUV and its cognate substrate-binding protein[J].J Biol Chem,2017,292(35):14617-14624. doi: 10.1074/jbc.M117.779975
54	THOMPSONJ M,JONESH A,PERRYR D.Molecular characterization of the hemin uptake locus (hmu) from Yersinia pestis and analysis of hmu mutants for hemin and hemoprotein utilization[J].Infect Immun,1999,67(8):3879-3892. doi: 10.1128/IAI.67.8.3879-3892.1999
55	EXNERT E,BECKERS,BECKERS,et al.Binding of HasA by its transmembrane receptor HasR follows a conformational funnel mechanism[J].Eur Biophys J,2020,49(1):39-57. doi: 10.1007/s00249-019-01411-1
56	ARNOUXP,HASERR,IZADIN,et al.The crystal structure of HasA, a hemophore secreted by Serratia marcescens[J].Nat Struct Biol,1999,6(6):516-520. doi: 10.1038/9281
57	GAOJ L,NGUYENK A,HUNTERN.Characterization of a hemophore-like protein from Porphyromonas gingivalis[J].J Biol Chem,2010,285(51):40028-40038. doi: 10.1074/jbc.M110.163535
58	HANSONM S,PELZELS E,LATIMERJ,et al.Identification of a genetic locus of Haemophilus influenzae type b necessary for the binding and utilization of heme bound to human hemopexin[J].Proc Natl Acad Sci U S A,1992,89(5):1973-1977. doi: 10.1073/pnas.89.5.1973
59	SMALLEYJ W,OLCZAKT.Heme acquisition mechanisms of Porphyromonas gingivalis-strategies used in a polymicrobial community in a heme-limited host environment[J].Mol Oral Microbiol,2017,32(1):1-23. doi: 10.1111/omi.12149
60	BATEMANT J,SHAHM,HOT P,et al.A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii[J].Nat Commun,2021,12(1):6270. doi: 10.1038/s41467-021-26545-9
61	CESCAUS,CWERMANH,LÉTOFFÉS,et al.Heme acquisition by hemophores[J].Biometals,2007,20(3-4):603-613. doi: 10.1007/s10534-006-9050-y
62	GUH W,LUC P.Selection of immunodominant mimics of IROMP-99 of rabbit Pasteurella multocida from a random 12-peptide library[J].Vet Microbiol,2006,115(4):339-348. doi: 10.1016/j.vetmic.2006.02.020
63	ROSSIM S,FETHERSTONJ D,LÉTOFFÉS,et al.Identification and characterization of the hemophore-dependent heme acquisition system of Yersinia pestis[J].Infect Immun,2001,69(11):6707-6717. doi: 10.1128/IAI.69.11.6707-6717.2001
64	HOLDENV I,BACHMANM A.Diverging roles of bacterial siderophores during infection[J].Metallomics,2015,7(6):986-995. doi: 10.1039/C4MT00333K
65	SAHAM,SARKARS,SARKARB,et al.Microbial siderophores and their potential applications: a review[J].Environ Sci Pollut Res Int,2016,23(5):3984-3999. doi: 10.1007/s11356-015-4294-0
66	KHANA,SINGHP,SRIVASTAVAA.Synthesis, nature and utility of universal iron chelator - siderophore: a review[J].Microbiol Res,2018,212-213,103-111. doi: 10.1016/j.micres.2017.10.012
67	殷奥杰,王齐,葛淼淼,等.微生物铁载体的应用研究进展[J].环境保护与循环经济,2021,41(7):20-24, 69.
	YINA J,WANGQ,GEM M,et al.The application and research progress of siderophore[J].Environmental Protection and Circular Economy,2021,41(7):20-24, 69.
68	HUS P,FELICEL J,SIVANANDANV,et al.Siderophore production by Pasteurella multocida[J].Infect Immun,1986,54(3):804-810.
69	CHOI-KIMK,MAHESWARANS K,FELICEL J,et al.Relationship between the iron regulated outer membrane proteins and the outer membrane proteins of in vivo grown Pasteurella multocida[J].Vet Microbiol,1991,28(1):75-92.
70	REISSBRODTR,ERLERW,WINKELMANNG.Iron supply of Pasteurella multocia and Pasteurella haemolotica[J].J Basic Microbiol,1994,34(1):61-63.
71	OGIERMANM,BRAUNV.Interactions between the outer membrane ferric citrate transporter FecA and TonB: studies of the FecA TonB box[J].J Bacteriol,2003,185(6):1870-1885.
72	NOINAJN,GUILLIERM,BARNARDT J,et al.TonB-dependent transporters: regulation, structure, and function[J].Annu Rev Microbiol,2010,64,43-60.
73	SUNY,ZHANGY,HOLLIBAUGHJ T,et al.Ecotype diversification of an abundant Roseobacter lineage[J].Environ Microbiol,2017,19(4):1625-1638.
74	AHMEDE,HOLMSTRÖMS J M.Siderophores in environmental research: roles and applications[J].Microb Biotechnol,2014,7(3):196-208.
75	WILSONB R,BOGDANA R,MIYAZAWAM,et al.Siderophores in iron metabolism: from mechanism to therapy potential[J].Trends Mol Med,2016,22(12):1077-1090.
76	CORNELISP,WEIQ,ANDREWSS C,et al.Iron homeostasis and management of oxidative stress response in bacteria[J].Metallomics,2011,3(6):540-549.
77	COSTAD,AMARELLEV,VALVERDEC,et al.The irr and RirA proteins participate in a complex regulatory circuit and act in concert to modulate bacterioferritin expression in Ensifer meliloti 1021[J].Appl Environ Microbiol,2017,83(16):e00895-17.
78	O'BRIANM R.Perception and homeostatic control of iron in the rhizobia and related bacteria[J].Annu Rev Microbiol,2015,69,229-245.
79	NONOYAMAS,KISHIDAK,SAKAIK,et al.A transcriptional regulator, IscR, of Burkholderia multivorans acts as both repressor and activator for transcription of iron-sulfur cluster-biosynthetic isc operon[J].Res Microbiol,2020,171(8):319-330.
80	POHLE,HALLERJ C,MIJOVILOVICHA,et al.Architecture of a protein central to iron homeostasis: crystal structure and spectroscopic analysis of the ferric uptake regulator[J].Mol Microbiol,2003,47(4):903-915.
81	BAICHOON,HELMANNJ D.Recognition of DNA by Fur: a reinterpretation of the Fur box consensus sequence[J].J Bacteriol,2002,184(21):5826-5832.
82	DELANYI,RAPPUOLIR,SCARLATOV.Fur functions as an activator and as a repressor of putative virulence genes in Neisseria meningitidis[J].Mol Microbiol,2004,52(4):1081-1090.
83	ESCOLARL,DE LORENZOV,PÉREZ-MARTÍNJ.Metalloregulation in vitro of the aerobactin promoter of Escherichia coli by the Fur (ferric uptake regulation) protein[J].Mol Microbiol,1997,26(4):799-808.
84	TROXELLB,HASSANH M.Transcriptional regulation by Ferric Uptake Regulator (Fur) in pathogenic bacteria[J].Front Cell Infect Microbiol,2013,3,59.
85	BOSCHM,TARRAGÓR,GARRIDOM E,et al.Expression of the Pasteurella multocida ompH gene is negatively regulated by the Fur protein[J].FEMS Microbiol Lett,2001,203(1):35-40.
86	EKINSA,NIVEND F.Identification of fur and fldA homologs and a Pasteurella multocida tbpA homolog in Histophilus ovis and effects of iron availability on their transcription[J].J Bacteriol,2002,184(9):2539-2542.
87	BAHRAMIF,NIVEND F.Iron acquisition by Actinobacillus suis: identification and characterization of a single-component haemoglobin receptor and encoding gene[J].Microb Pathog,2005,39(1-2):45-51.
88	COXA J,HUNTM L,BOYCEJ D,et al.Functional characterization of HgbB, a new hemoglobin binding protein of Pasteurella multocida[J].Microb Pathog,2003,34(6):287-296.
89	LIUQ,HUY L,LIP,et al.Identification of Fur in Pasteurella multocida and the potential of its mutant as an attenuated live vaccine[J].Front Vet Sci,2019,6,5.
90	TEIXIDÓL,CARRASCOB,ALONSOJ C,et al.Fur activates the expression of Salmonella enterica pathogenicity island 1 by directly interacting with the hilD operator in vivo and in vitro[J].PLoS One,2011,6(5):e19711.
91	BERESWILLS,GREINERS,VAN VLIETA H M,et al.Regulation of ferritin-mediated cytoplasmic iron storage by the ferric uptake regulator homolog (Fur) of Helicobacter pylori[J].J Bacteriol,2000,182(21):5948-5953.
92	GUOM L,GAOM M,LIUJ J,et al.Bacterioferritin nanocage: Structure, biological function, catalytic mechanism, self-assembly and potential applications[J].Biotechnol Adv,2022,61,108057.
93	YAOH L,SOLDANOA,FONTENOTL,et al.Pseudomonas aeruginosa bacterioferritin is assembled from FtnA and BfrB subunits with the relative proportions dependent on the environmental oxygen availability[J].Biomolecules,2022,12(3):366.
94	NANDALA,HUGGINSC C O,WOODHALLM R,et al.Induction of the ferritin gene (ftnA) of Escherichia coli by Fe²⁺-Fur is mediated by reversal of H-NS silencing and is RyhB independent[J].Mol Microbiol,2010,75(3):637-657.
95	EWERSC,LÜBKE-BECKERA,BETHEA,et al.Virulence genotype of Pasteurella multocida strains isolated from different hosts with various disease status[J].Vet Microbiol,2006,114(3-4):304-317.
96	KATSUDAK,HOSHINOOK,UENOY,et al.Virulence genes and antimicrobial susceptibility in Pasteurella multocida isolates from calves[J].Vet Microbiol,2013,167(3-4):737-741.
97	LIUS T,LINL,YANGH,et al.Pasteurella multocida capsular: lipopolysaccharide types D: L6 and A: L3 remain to be the main epidemic genotypes of pigs in China[J].Anim Dis,2021,1(1):26.

[1]	刘博华, 符汉宇, 王玉恒, 索朗斯珠, 牛家强, 包玉花, 李家奎, 徐业芬. 西藏那曲市牦牛源B型多杀性巴氏杆菌的分离鉴定及基因组分析[J]. 畜牧兽医学报, 2024, 55(7): 3105-3118.
[2]	高洁, 李晓成, 穆杨, 张慧, 魏荣, 李劼. 荚膜B型多杀性巴氏杆菌外膜囊泡生物学特性分析与免疫效果评价[J]. 畜牧兽医学报, 2024, 55(5): 2168-2175.
[3]	许文博, 吴丽梅, 刘鑫, 李升, 黄复深, 李润成. 1株多杀性巴氏杆菌的全基因组序列及致病相关基因分析[J]. 畜牧兽医学报, 2022, 53(6): 1858-1869.
[4]	王斐, 杨洁, 吕庆杰, 王米雪, 刘鹏, 张若愚, 史聪聪, 王雪莹, 林琳, 华琳, 宋文博, 梁婉, 陈焕春, 吴斌, 彭忠. 致脑膜炎多杀性巴氏杆菌的分离鉴定及全基因组重测序[J]. 畜牧兽医学报, 2022, 53(12): 4346-4355.
[5]	杨洋, 谢黎卿, 胡沛, 高丽旭, 袁祥, 李攀, 彭远义, 李能章. 牛源A型多杀性巴氏杆菌hyaD基因缺失株的构建及其在小鼠上的交叉保护性分析[J]. 畜牧兽医学报, 2022, 53(10): 3582-3597.
[6]	李甜, 杨洋, 谢黎卿, 王远兰, 李攀, 彭远义, 李能章. 牛溶血性曼氏杆菌及牛荚膜A型多杀性巴氏杆菌灭活疫苗对小鼠的保护性研究[J]. 畜牧兽医学报, 2021, 52(9): 2579-2588.
[7]	张亚楠, 李亚菲, 陈汝佳, 余波, 彭珊, 李婷, 蒲龄, 徐景峨. A:L1 ST128型鸭源多杀性巴氏杆菌的耐药性及毒力分析[J]. 畜牧兽医学报, 2021, 52(10): 2852-2863.
[8]	涂健, 蔡伟真, 阮苑, 宋祥军, 邵颖, 祁克宗. Fur/RyhB调控禽致病性大肠杆菌运动性机制的研究[J]. 畜牧兽医学报, 2020, 51(2): 346-355.
[9]	彭忠, 梁婉, 艾伟诚, 王斐, 华琳, 汤细彪, 陈焕春, 吴斌. 我国猪群中多杀性巴氏杆菌的基因型分析[J]. 畜牧兽医学报, 2019, 50(5): 1064-1072.
[10]	李艳红, 刘洁, 李伟平, 崔雨婷, 彭远义, 吴正理. 牛A型巴氏杆菌高、低毒力株LPS激活RAW264.7细胞TLR4信号通路的比较分析[J]. 畜牧兽医学报, 2019, 50(3): 620-626.
[11]	梁圣, 赵新新, 程安春. 禽霍乱新型疫苗的研究进展[J]. 畜牧兽医学报, 2018, 49(11): 2317-2325.
[12]	华瑞其，赵新新，程安春. 多杀性巴氏杆菌脂多糖的结构与功能研究进展[J]. 畜牧兽医学报, 2016, 47(10): 1961-1968.
[13]	曹长福，孙美珍，卢燕，曾庆林，刘伟，曾振灵. 肌注马波沙星在犊黄牛体内的药动学及半体内抗菌后效应研究[J]. 畜牧兽医学报, 2015, 46(11): 2078-2084.
[14]	黄海燕;王印;彭娟;宋勇;蒋梅;钟霏;李丽瑞. 猪源多杀性巴氏杆菌PCR鉴定方法的建立[J]. 畜牧兽医学报, 2012, 43(7): 1111-1116.
[15]	肖国生;;曹三杰;黄小波;文心田. 猪胸膜肺炎放线杆菌、肺炎支原体和多杀性巴氏杆菌联合检测芯片的研制及应用[J]. 畜牧兽医学报, 2010, 41(1): 77-85.