鸡毒支原体MIB-MIP免疫球蛋白逃逸系统的宿主特异性及水平基因转移
Host specificity and horizontal gene transfer in the MIB-MIP immunoglobulin evasion system in Mycoplasma gallisepticum.
Host specificity and horizontal gene transfer in the MIB-MIP immunoglobulin evasion system in Mycoplasma gallisepticum.
鸡毒支原体是一种主要的禽类病原体,可引起慢性呼吸道疾病并造成全球重大经济损失。其建立慢性感染的能力反映了其有效的免疫逃逸策略,但其潜在机制仍知之甚少。一些致病性哺乳动物支原体利用支原体免疫球蛋白结合蛋白酶(Mycoplasma Immunoglobulin Binding-Protease,MIB-MIP)系统来捕获并切割宿主免疫球蛋白(Ig),但该系统在鸡毒支原体中的功能及宿主特异性尚未得到研究。本研究旨在对鸡毒支原体中所有MIB-MIP同源物进行功能鉴定,并考察其宿主特异性。研究克隆了鸡毒支原体的5个推定MIB基因和5个推定MIP基因,以重组GST融合蛋白形式表达并纯化用于功能分析。免疫球蛋白结合实验显示,所有MIB蛋白均可结合禽类和哺乳动物免疫球蛋白,形成稳定的MIB-Ig复合物,且结合能力存在差异。相比之下,蛋白水解实验揭示,5个MIP蛋白中仅3个在与5个MIB中任一形成复合物时能够切割禽类免疫球蛋白,产生特征性Ig重链片段。仅1个MIP蛋白酶与哺乳动物免疫球蛋白表现出可检测的相互作用,表明这些MIP具有强宿主特异性及针对禽类免疫球蛋白切割的功能特化。这些结果揭示,鸡毒支原体的MIB和MIP蛋白适应于切割禽类免疫球蛋白,从而干扰抗体介导的宿主免疫应答。生物信息学分析提示,MIB-MIP同源物在具有相似宿主、组织嗜性和传播模式的禽类支原体中广泛存在,并检测到水平基因转移和重组的证据,表明禽类支原体间存在MIB-MIP的进化适应。
Mycoplasma gallisepticum is a major poultry pathogen responsible for chronic respiratory disease and substantial global economic losses. Its ability to establish chronic infections reflects its effective immune evasion strategies, but the mechanisms underlying this remain poorly understood. Some pathogenic mammalian mycoplasmas use the Mycoplasma Immunoglobulin Binding-Protease (MIB-MIP) system to capture and cleave host immunoglobulins (Ig), but the functionality and host-specificity of this system in M. gallisepticum have not been examined. We aimed to functionally characterise all the MIB-MIP homologues in M. gallisepticum and examine their host specificity. Five putative MIB and five putative MIP genes of M. gallisepticum were cloned, expressed as recombinant GST-fusion proteins, and purified for functional analysis. Immunoglobulin-binding assays showed that all MIB proteins bound both avian and mammalian immunoglobulins, forming stable MIB-Ig complexes, with distinct binding capacities. In contrast, proteolytic assays revealed that only three of the five MIP proteins could cleave avian immunoglobulins, when complexed with any of the five MIBs, generating characteristic Ig heavy-chain fragments. Only one MIP protease showed detectable interaction with mammalian immunoglobulins, indicating strong host specificity of these MIPs and functional specialisation for avian immunoglobulin-cleavage. These results revealed that MIB and MIP proteins of M. gallisepticum are adapted to cleavage of avian immunoglobins, thereby interfering with antibody-mediated host immune responses. Bioinformatic analysis suggested that MIB-MIP homologues are widespread among avian mycoplasmas that share similar hosts, tissue tropisms and transmission patterns, and detected evidence of horizontal gene transfer and recombination, indicating that there have been MIB-MIP evolutionary adaptations among the avian mycoplasmas.
Dilhani Ekanayake, Paola Vaz, Alistair R Legione, Nadeeka K Wawegama, Glenn F Browning, Kelly A Tivendale. Host specificity and horizontal gene transfer in the MIB-MIP immunoglobulin evasion system in Mycoplasma gallisepticum.. Veterinary research. 2026; doi:10.1186/s13567-026-01779-x.
Dilhani Ekanayake, Paola Vaz, Alistair R Legione, Nadeeka K Wawegama, Glenn F Browning, Kelly A Tivendale (2026). Host specificity and horizontal gene transfer in the MIB-MIP immunoglobulin evasion system in Mycoplasma gallisepticum.. Veterinary research. https://doi.org/10.1186/s13567-026-01779-x
Dilhani Ekanayake, Paola Vaz, Alistair R Legione, Nadeeka K Wawegama, Glenn F Browning, Kelly A Tivendale. Host specificity and horizontal gene transfer in the MIB-MIP immunoglobulin evasion system in Mycoplasma gallisepticum.[J]. Veterinary research, 2026 doi:10.1186/s13567-026-01779-x.
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