Center for Microbial Dynamics & Infection, School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Microbiology (Reading). 2022 Dec;168(12). doi: 10.1099/mic.0.001265.
uses quorum sensing (QS) to coordinate the expression of multiple genes necessary for establishing and maintaining infection. It has previously been shown that QS mutations frequently arise in cystic fibrosis (CF) lung infections, however, there has been far less emphasis on determining whether other QS system mutations arise during infection or in other environments. To test this, we utilized 852 publicly available sequenced genomes from the International Consortium Database (IPCD) to study QS mutational signatures. To study isolates by source, we focused on a subset of 654 isolates collected from CF, wounds, and non-infection environmental isolates, where we could clearly identify their source. We also worked with a small collection of isolates to determine the impact of and mutations on isolate phenotypes. We found that mutations are common across all environments and are not specific to infection nor a particular infection type. We also found that the system proteins PqsA, PqsH, PqsL and MexT, a protein of increasing importance to the QS field, are highly variable. Conversely, RsaL, a negative transcriptional regulator of the system, was found to be highly conserved, suggesting selective pressure to repress system activity. Overall, our findings suggest that QS mutations in are common and not limited to the system; however, LasR is unique in the frequency of putative loss-of-function mutations.
它利用群体感应(QS)来协调建立和维持感染所需的多个基因的表达。先前的研究表明,QS 突变在囊性纤维化(CF)肺部感染中经常发生,然而,对于确定其他 QS 系统突变是否在感染期间或在其他环境中发生,关注程度要低得多。为了检验这一点,我们利用来自国际合作数据库(IPCD)的 852 个公开可用的测序基因组来研究 QS 突变特征。为了按来源研究分离株,我们集中研究了从 CF、伤口和非感染环境分离株中收集的 654 个分离株的子集,我们可以清楚地识别它们的来源。我们还与一小部分分离株合作,以确定和突变对分离株表型的影响。我们发现突变在所有环境中都很常见,既不是感染特有的,也不是特定感染类型特有的。我们还发现,QS 系统蛋白 PqsA、PqsH、PqsL 和 MexT,一个对 QS 领域越来越重要的蛋白,高度可变。相反,RsaL,QS 系统的负转录调节因子,被发现高度保守,这表明存在抑制 QS 系统活性的选择压力。总的来说,我们的研究结果表明,在中 QS 突变是常见的,不限于系统;然而,LasR 在潜在的功能丧失突变的频率方面是独特的。