Mesh : Bacterial Vaccines / immunology genetics Mycoplasma / genetics immunology Animals Bacterial Proteins / genetics metabolism Immunoglobulins / genetics metabolism immunology Gene Expression Regulation, Bacterial Mycoplasma Infections / veterinary microbiology immunology prevention & control Goats

来  源:   DOI:10.1038/s42003-024-06497-8   PDF(Pubmed)

Abstract:
The Mycoplasma Immunoglobulin Binding/Protease (MIB-MIP) system is a candidate \'virulence factor present in multiple pathogenic species of the Mollicutes, including the fast-growing species Mycoplasma feriruminatoris. The MIB-MIP system cleaves the heavy chain of host immunoglobulins, hence affecting antigen-antibody interactions and potentially facilitating immune evasion. In this work, using -omics technologies and 5\'RACE, we show that the four copies of the M. feriruminatoris MIB-MIP system have different expression levels and are transcribed as operons controlled by four different promoters. Individual MIB-MIP gene pairs of M. feriruminatoris and other Mollicutes were introduced in an engineered M. feriruminatoris strain devoid of MIB-MIP genes and were tested for their functionality using newly developed oriC-based plasmids. The two proteins are functionally expressed at the surface of M. feriruminatoris, which confirms the possibility to display large membrane-associated proteins in this bacterium. However, functional expression of heterologous MIB-MIP systems introduced in this engineered strain from phylogenetically distant porcine Mollicutes like Mesomycoplasma hyorhinis or Mesomycoplasma hyopneumoniae could not be achieved. Finally, since M. feriruminatoris is a candidate for biomedical applications such as drug delivery, we confirmed its safety in vivo in domestic goats, which are the closest livestock relatives to its native host the Alpine ibex.
摘要:
支原体免疫球蛋白结合/蛋白酶(MIB-MIP)系统是一种候选的毒力因子,包括快速生长的阿氏支原体。MIB-MIP系统切割宿主免疫球蛋白的重链,因此影响抗原-抗体相互作用并可能促进免疫逃避。在这项工作中,使用-组学技术和5'RACE,我们表明,四个拷贝的费氏支原体MIB-MIP系统具有不同的表达水平,并被转录为由四个不同启动子控制的操纵子。在不含MIB-MIP基因的工程化费氏支原体菌株中引入了费氏支原体和其他Mollicutes的单个MIB-MIP基因对,并使用新开发的基于oriC的质粒测试了它们的功能。这两种蛋白质在费氏支原体的表面功能性表达,这证实了在这种细菌中展示大型膜相关蛋白的可能性。然而,无法实现从系统发育上遥远的猪毛囊,例如猪肺炎中支原体或猪肺炎中支原体,在该工程菌株中引入的异源MIB-MIP系统的功能表达。最后,由于费氏支原体是生物医学应用的候选药物,如药物递送,我们证实了它在家养山羊体内的安全性,它们是它的本土寄主阿尔卑斯山牛最亲密的牲畜亲戚。
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