School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
Bristol Centre for Functional Nanomaterials, HH Wills Physics Laboratory, University of Bristol, Bristol, UK.
Microb Genom. 2020 May;6(5). doi: 10.1099/mgen.0.000372. Epub 2020 May 4.
Mobile genetic elements (MGEs) are key factors responsible for dissemination of virulence determinants and antimicrobial-resistance genes amongst pathogenic bacteria. Conjugative MGEs are notable for their high gene loads donated per transfer event, broad host ranges and phylogenetic ubiquity amongst prokaryotes, with the subclass of chromosomally inserted integrative and conjugative elements (ICEs) being particularly abundant. The focus on a small number of model systems has biased the study of ICEs towards those conferring readily selectable phenotypes to host cells, whereas the identification and characterization of integrated cryptic elements remains challenging. Even though antimicrobial resistance and horizontally acquired virulence genes are major factors aggravating neisserial infection, conjugative MGEs of and remain poorly characterized. Using a phenotype-independent approach based on atypical distributions of DNA uptake sequences (DUSs) in MGEs relative to the chromosomal background, we have identified two groups of chromosomally integrated conjugative elements in : one found almost exclusively in pathogenic species possibly deriving from the genus , the other belonging to a group of -like commensals. The former element appears to enable transfer of traditionally gonococcal-specific loci such as the virulence-associated toxin-antitoxin system to chromosomes, whilst the circular form of the latter possesses a unique attachment site () sequence seemingly adapted to exploit DUS motifs as chromosomal integration sites. In addition to validating the use of DUS distributions in MGE identification, the >170 identified ICE sequences provide a valuable resource for future studies of ICE evolution and host adaptation.
移动遗传元件(MGEs)是导致病原菌毒力决定因素和抗微生物药物耐药基因传播的关键因素。可移动 MGEs 的特点是每次转移事件中捐赠的高基因负荷、广泛的宿主范围和原核生物中的系统发育普遍性,其中插入染色体的整合和可移动元件(ICEs)亚类特别丰富。对少数模型系统的关注使 ICEs 的研究偏向于那些易于赋予宿主细胞可选择表型的 ICEs,而整合隐式元件的识别和表征仍然具有挑战性。尽管抗微生物药物耐药性和水平获得的毒力基因是加剧奈瑟菌感染的主要因素,但 和 的可移动 MGEs 仍未得到充分描述。我们使用一种基于 MGE 中 DNA 摄取序列(DUS)相对于染色体背景的非典型分布的表型独立方法,在 中鉴定了两组染色体整合的可移动元件:一组几乎只存在于可能源自属的致病性物种中,另一组属于类似于属的共生菌。前者元件似乎能够将传统的淋球菌特异性基因座,如与毒力相关的毒素-抗毒素系统,转移到 染色体上,而后者的圆形形式则具有独特的附着位点()序列,似乎适应利用 DUS 基序作为染色体整合位点。除了验证 DUS 分布在 MGE 识别中的使用外,超过 170 个鉴定的 ICE 序列为未来的 ICE 进化和宿主适应研究提供了有价值的资源。