A6型牛溶血性曼氏杆菌生物学特性研究及免疫原性评价

doi:10.11843/j.issn.0366-6964.2025.05.029

摘要/Abstract

摘要：

牛溶血性曼氏杆菌(Mannheimia haemolytica，Mh)是引起牛呼吸道疾病(bovine respiratory disease，BRD)的最主要病原之一，严重影响牛群的健康养殖及食品安全。本研究采集了伴有发热、流鼻涕等呼吸道症状的犊牛鼻拭子进行细菌分离培养，并对分离株进行血清型鉴定、16S rRNA测序分析和PCR分型，测试了分离菌株对15种抗生素的耐药表型；同时通过小鼠死亡率以及临床剖检结果对小鼠作为Mh替代动物感染模型的可能性进行评估，构建小鼠细菌感染模型，并评估了分离株的致病性与免疫原性。结果显示：分离株纯化后经鉴定为A6型牛溶血性曼氏杆菌，将其命名为KQ-Mh-1。该菌株对阿米卡星、美洛西林、庆大霉素、链霉素、阿莫西林和磺胺异恶唑等多种药物耐药，对头孢噻肟、诺氟沙星、头孢哌酮、环丙沙星、多黏菌素、新霉素和多西环素表现出较高的敏感性。分离株KQ-Mh-1对BALB/c小鼠的半数致死量(LD₅₀)为7.29×10⁹ CFU ·mL^-1，感染死亡小鼠均表现为肺脏、脾脏严重出血。将KQ-Mh-1制备成不同抗原含量的灭活疫苗进行其免疫原性评估，其中高抗原含量(2.5×10¹⁰ CFU ·mL^-1)的灭活疫苗免疫小鼠后对于A6型溶血性曼氏杆菌的攻毒具有70%的保护率。本研究成功分离出一株可导致牛BRD的Mh菌株，并对其生物学特性、致病性和免疫原性进行探究，为牛BRD疫苗的研发提供了良好的疫苗候选菌株。

关键词: 牛呼吸道疾病, 溶血性曼氏杆菌, 小鼠模型, 灭活疫苗

Abstract:

Mannheimia haemolytica (Mh) is one of the most important pathogens causing bovine respiratory disease (BRD), which seriously affects the healthy breeding and food safety of cattle. In this study, nasal swabs of calves with respiratory symptoms such as fever and runny nose were collected for bacterial isolation and culture, and serotype identification, 16S rRNA sequencing analysis and PCR typing of the isolates were performed. The drug-resistant phenotype of the isolates to 15 antibiotics was tested, the possibility of mice as Mh replacement animal infection models was evaluated by mortality and pathological changes of the mice. A mouse bacterial infection model was constructed, and the pathogenicity and immunogenicity of the isolates were evaluated. The results showed that the purified strain was identified as Mh and named KQ-Mh-1.The strain was resistant to amicacin, melocillin, gentamicin, streptomycin, amoxicillin and sulfamethoxazole, and showed high sensitivity to cefotaxime, norfloxacin, cefoperazone, ciprofloxacin, polymyxin, neomycin and doxycycline. The median lethal dose (LD₅₀) of KQ-Mh-1 on BALB/c mice was 7.29×10⁹ CFU ·mL^-1, and the infected mice all showed severe hemorrhages in the lung and spleen. KQ-Mh-1 was prepared into inactivated vaccines with different antigen content to evaluate its immunogenicity, in which the inactivated vaccine with high antigen content (2.5×10¹⁰ CFU ·mL^-1) had a 70% protection rate against KQ-Mh-1 after immunizing mice. In this study, a Mh strain that can cause bovine BRD was successfully isolated and its biological characteristics, pathogenicity and immunogenicity were investigated, which provided a good vaccine candidate strain for the research and development of bovine BRD vaccine.

Key words: bovine respiratory disease, Mannheimia haemolytica, mice model, inactivated vaccine

中图分类号:

S852.612

贾超莹, 张华伟, 罗修鑫, 刘青芸, 王湘如. A6型牛溶血性曼氏杆菌生物学特性研究及免疫原性评价[J]. 畜牧兽医学报, 2025, 56(5): 2312-2324.

JIA Chaoying, ZHANG Huawei, LUO Xiuxin, LIU Qingyun, WANG Xiangru. Establishment of Mice Model Infected by Bovine Mannheimia haemolytica and the Immunogenicity of Inactivated Vaccine[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(5): 2312-2324.

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分型 Typing	引物序列(5′→3′) Primer sequence	目的片段大小/bp Product lenth
A1型Type A1	F: CATTTCCTTAGGTTCAGC R: CAAGTCATCGTAATGCCT	306
A2型Type A2	F: GGCATATCCTAAAGCCGT R: AGAATCCACTATTGGGCACC	160
A6型Type A6	F: TGAGAATTTCGACAGCACT R: ACCTTGGCATATCG-TACC	78

抗生素 Antibiotic	含量/(μg·片^-1) Content	判定标准 Standard of criterion			抑菌圈直径/mm Diameter of inhibition zone	判定 Judgement
抗生素 Antibiotic	含量/(μg·片^-1) Content	耐药	中介	敏感	抑菌圈直径/mm Diameter of inhibition zone	判定 Judgement
头孢噻肟 Cefotaxime	30	≤25	＞25~＜33	≥33	35	敏感
诺氟沙星 Norfloxacin	10	≤15	＞15~＜21	≥21	22	敏感
头孢哌酮 Cefoperazone	75	≤12	＞12~＜17	≥17	21	敏感
左氧氟沙星 Levofloxacin	5	≤19	＞19~＜26	≥26	23	中介
阿米卡星 Amikacin	30	≤19	＞19~＜26	≥26	11	耐药
美洛西林 Mezlocillin	75	≤17	＞17~＜21	≥21	0	耐药
妥布霉素 Tobramycin	10	≤12	＞12~＜17	≥17	14	中介
庆大霉素 Gentamycin	10	≤19	＞19~＜26	≥26	12	耐药
环丙沙星 Ciprofloxacin	5	≤15	＞15~＜21	≥21	22	敏感
多黏菌素 Polymyxin	300	≤13	＞13~＜19	≥19	20	敏感
新霉素 Neomycin	30	≤12	＞12~＜17	≥17	19	敏感
链霉素 Streptomycin	10	≤12	＞12~＜17	≥20	0	耐药
多西环素 Doxycycline	30	≤18	＞18~＜24	≥24	26	敏感
阿莫西林 Amoxicillin	20	≤13	＞13~＜21	≥21	0	耐药
磺胺异恶唑 Sulfisoxazole	250	≤15	＞15~＜23	≥23	0	耐药

菌液浓度/(CFU·mL^-1) Concentration of bacterium	剂量/mL Dosage	死亡率 Mortality	半数致死量/(CFU·mL^-1) Median lethal dose
4.05×10¹⁰	0.2	4/6	7.29×10⁹
4.05×10⁹	0.2	3/6
4.05×10⁸	0.2	1/6
4.05×10⁷	0.2	0/6
4.05×10⁶	0.2	0/6

组别 Group	抗原含量/(CFU·mL^-1) Antigenic content	免疫剂量/mL Immunizing dose	攻毒菌量/(CFU·只^-1) Challenged bacteria amount	保护率 Protective rate
免疫组	2.5×10¹⁰	0.2	1.56×10¹⁰	7/10
Immunized group	1.0×10¹⁰	0.2	1.56×10¹⁰	5/10
	5.0×10⁹	0.2	1.56×10¹⁰	1/10
未免疫组 Non immunized group	0	0.2	1.56×10¹⁰	0/10

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