Theiss P, Wise K S
Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri-Columbia, 65212, USA.
J Bacteriol. 1997 Jun;179(12):4013-22. doi: 10.1128/jb.179.12.4013-4022.1997.
The wall-less mycoplasmas have revealed unusual microbial strategies for adaptive variation of antigenic membrane proteins exposed during their surface colonization of host cells. In particular, high-frequency mutations affecting the expression of selected surface lipoproteins have been increasingly documented for this group of organisms. A novel manifestation of mutational phase variation is shown here to occur in Mycoplasma fermentans, a chronic human infectious agent and possible AIDS-associated pathogen. A putative ABC type transport operon encoding four gene products is identified. The 3' distal gene encoding P78, a known surface-exposed antigen and the proposed substrate-binding lipoprotein of the transporter, is subject to localized hypermutation in a short homopolymeric tract of adenine residues located in the N-terminal coding region of the mature product. High-frequency, reversible insertion/deletion frameshift mutations lead to selective phase variation in P78 expression, whereas the putative nucleotide-binding protein, P63, encoded by the most 5' gene of the operon, is continually expressed. Mutation-based phase variation in specific surface-exposed microbial transporter components may provide an adaptive advantage for immune evasion, while continued expression of other elements of the same transporter may preserve essential metabolic functions and confer alternative substrate specificity. These features could be critical in mycoplasmas, where limitations in both transcriptional regulators and transport systems may prevail. This study also documents that P63 contains an uncharacteristic hydrophobic sequence between predicted nucleotide binding motifs and displays an amphiphilic character in detergent fractionation. Both features are consistent with an evolutionary adaptation favoring integral association of this putative energy-transducing component with the single mycoplasma membrane.
无细胞壁的支原体在宿主细胞表面定植过程中，展现出了抗原性膜蛋白适应性变异的独特微生物策略。特别是，越来越多的文献记载了影响特定表面脂蛋白表达的高频突变在这类生物体中的存在。本文展示了一种新的突变相变异表现形式，它发生在发酵支原体中，这是一种慢性人类感染因子，也是可能与艾滋病相关的病原体。我们鉴定出了一个假定的ABC型转运操纵子，它编码四种基因产物。编码P78的3'端远端基因，P78是一种已知的表面暴露抗原，也是该转运体中拟议的底物结合脂蛋白，在成熟产物N端编码区的一段腺嘌呤残基短同聚物区域发生局部高突变。高频、可逆的插入/缺失移码突变导致P78表达的选择性相变异，而由操纵子最5'端基因编码的假定核苷酸结合蛋白P63则持续表达。特定表面暴露的微生物转运体成分中基于突变的相变异可能为免疫逃避提供适应性优势，而同一转运体其他元件的持续表达可能保留基本代谢功能并赋予替代底物特异性。这些特征在支原体中可能至关重要，因为转录调节因子和转运系统可能都存在局限性。本研究还证明，P63在预测的核苷酸结合基序之间包含一个不寻常的疏水序列，并且在去污剂分级分离中表现出两亲性。这两个特征都与一种进化适应性一致，这种适应性有利于这种假定的能量转导成分与单一的支原体膜进行整体结合。
