Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
Department of Embryology, Carnegie Institution for Science, Baltimore, Maryland, United States of America.
PLoS One. 2022 Jul 6;17(7):e0270576. doi: 10.1371/journal.pone.0270576. eCollection 2022.
Pseudomonas aeruginosa is a significant threat in healthcare settings where it deploys a wide host of virulence factors to cause disease. Many virulence-related phenotypes such as pyocyanin production, biofilm formation, and twitching motility have been implicated in causing disease in a number of hosts. In this study, we investigate these three virulence factors in a collection of 22 clinical strains isolated from blood stream infections. Despite the fact that all 22 strains caused disease and came from the same body site of different patients, they show significant variability in assays for each of the three specific phenotypes examined. There was no significant correlation between the strength of the three phenotypes across our collection, suggesting that they can be independently modulated. Furthermore, strains deficient in each of the virulence-associated phenotypes examined could be identified. To understand the genetic basis of this variability we sequenced the genomes of the 22 strains. We found that the majority of genes responsible for pyocyanin production, biofilm formation, and twitching motility were highly conserved among the strains despite their phenotypic variability, suggesting that the phenotypic variability is likely due to regulatory changes. Our findings thus demonstrate that no one lab-assayed phenotype of pyocyanin production, biofilm production, and twitching motility is necessary for a P. aeruginosa strain to cause blood stream infection and that additional factors may be needed to fully predict what strains will lead to specific human diseases.
铜绿假单胞菌是医疗环境中的一个重大威胁,它会利用多种毒力因子来引发疾病。许多与毒力相关的表型,如绿脓菌素的产生、生物膜的形成和蠕动运动,都与在多种宿主中引起疾病有关。在这项研究中,我们研究了来自血流感染的 22 株临床分离株中的这三种毒力因子。尽管所有 22 株菌都导致了疾病,并且都来自不同患者的同一身体部位,但它们在三种特定表型的检测中表现出显著的变异性。在我们的研究中,这三种表型之间没有显著的相关性,这表明它们可以独立调节。此外,还可以鉴定出每种毒力相关表型缺陷的菌株。为了了解这种变异性的遗传基础,我们对 22 株菌的基因组进行了测序。我们发现,尽管表型存在变异性,但负责绿脓菌素产生、生物膜形成和蠕动运动的大多数基因在菌株之间高度保守,这表明表型变异性可能是由于调控变化引起的。因此,我们的研究结果表明,绿脓菌素产生、生物膜形成和蠕动运动的任何一种实验室检测表型都不是铜绿假单胞菌引起血流感染所必需的,可能还需要其他因素来充分预测哪些菌株会导致特定的人类疾病。