Seubert Anja, Hiestand Rosemarie, de la Cruz Fernando, Dehio Christoph
Division of Molecular Microbiology, Biozentrum of the University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Mol Microbiol. 2003 Sep;49(5):1253-66. doi: 10.1046/j.1365-2958.2003.03650.x.
Type IV secretion systems (T4SS) are multicomponent transporters of Gram-negative bacteria adapted to functions as diverse as DNA transfer in bacterial conjugation or the delivery of effector proteins into eukaryotic target cells in pathogenesis. The generally modest sequence conservation between T4SS may reflect their evolutionary distance and/or functional divergence. Here, we show that the establishment of intraerythrocytic parasitism by Bartonella tribocorum requires a putative T4SS, which shares an unprecedented level of sequence identity with the Trw conjugation machinery of the broad-host-range antibiotic resistance plasmid R388 (up to 80% amino acid identity for individual T4SS components). The highly conserved T4SS loci are collinear except for the presence of numerous tandem gene duplications in B. tribocorum, which mostly encode variant forms of presumed surface-exposed pilus subunits. Conservation is not only structural, but also functional: R388 mutated in either trwD or trwH encoding essential T4SS components could be trans-complemented for conjugation by the homologues of the B. tribocorum system. Conservation also includes the transcription regulatory circuit: both T4SS loci encode a highly homologous and interchangeable KorA/KorB repressor system that negatively regulates the expression of all T4SS components. This striking example of adaptive evolution reveals the capacity of T4SS to assume dedicated functions in either DNA transfer or pathogenesis over rather short evolutionary distance and implies a novel role for the conjugation systems of widespread broad-host-range plasmids in the evolution of bacterial pathogens.
IV型分泌系统（T4SS）是革兰氏阴性菌的多组分转运蛋白，适用于多种功能，如细菌接合中的DNA转移或发病机制中效应蛋白向真核靶细胞的递送。T4SS之间通常适度的序列保守性可能反映了它们的进化距离和/或功能差异。在这里，我们表明，三宿主巴尔通体建立红细胞内寄生需要一个假定的T4SS，它与广泛宿主范围的抗生素抗性质粒R388的Trw接合机制具有前所未有的序列同一性水平（单个T4SS组分的氨基酸同一性高达80%）。高度保守的T4SS基因座是共线的，除了三宿主巴尔通体中存在大量串联基因重复，这些重复大多编码假定的表面暴露菌毛亚基的变体形式。保守不仅是结构上的，也是功能上的：在编码必需T4SS组分的trwD或trwH中发生突变的R388可以通过三宿主巴尔通体系统的同源物进行反式互补以进行接合。保守还包括转录调节回路：两个T4SS基因座都编码高度同源且可互换的KorA/KorB阻遏系统，该系统负调节所有T4SS组分的表达。这个适应性进化的显著例子揭示了T4SS在相当短的进化距离内承担DNA转移或发病机制中特定功能的能力，并暗示了广泛存在的广泛宿主范围质粒的接合系统在细菌病原体进化中的新作用。
