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严重热损伤患者血液中铜绿假单胞菌生长伴随主要转录组变化。

Major Transcriptome Changes Accompany the Growth of Pseudomonas aeruginosa in Blood from Patients with Severe Thermal Injuries.

作者信息

Kruczek Cassandra, Kottapalli Kameswara Rao, Dissanaike Sharmila, Dzvova Nyaradzo, Griswold John A, Colmer-Hamood Jane A, Hamood Abdul N

机构信息

Department of Surgery, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.

Center for Biotechnology and Genomics, Texas Tech University, Lubbock, Texas, United States of America.

出版信息

PLoS One. 2016 Mar 2;11(3):e0149229. doi: 10.1371/journal.pone.0149229. eCollection 2016.

Abstract

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes serious infections in immunocompromised hosts including severely burned patients. After multiplying within the burn wound, P. aeruginosa translocate into the bloodstream causing bacterial sepsis frequently leading to organ dysfunction and septic shock. Although the pathogenesis of P. aeruginosa infection of thermally-injured wounds has been extensively analyzed, little is known regarding the ability of P. aeruginosa to adapt and survive within the blood of severely burned patients during systemic infection. To identify such adaptations, transcriptome analyses (RNA-seq) were conducted on P. aeruginosa strain PA14 that was grown in whole blood from a healthy volunteer or three severely burned patients. Compared with growth in blood from healthy volunteers, growth of PA14 in the blood from severely burned patients significantly altered the expression of 2596 genes, with expression of 1060 genes enhanced, while that of 1536 genes was reduced. Genes whose expression was significantly reduced included genes related to quorum sensing, quorum sensing-controlled virulence factors and transport of heme, phosphate, and phosphonate. Genes whose expression was significantly enhanced were related to the type III secretion system, the pyochelin iron-acquisition system, flagellum synthesis, and pyocyanin production. We confirmed changes in expression of many of these genes using qRT-PCR. Although severe burns altered the levels of different blood components in each patient, the growth of PA14 in their blood produced similar changes in the expression of each gene. These results suggest that, in response to changes in the blood of severely burned patients and as part of its survival strategy, P. aeruginosa enhances the expression of certain virulence genes and reduces the expression of others.

摘要

铜绿假单胞菌是一种革兰氏阴性机会致病菌,可在包括严重烧伤患者在内的免疫功能低下宿主中引起严重感染。在烧伤创面内繁殖后,铜绿假单胞菌会转移至血液中,引发细菌性败血症,常导致器官功能障碍和感染性休克。尽管对热损伤创面铜绿假单胞菌感染的发病机制已进行了广泛分析,但对于铜绿假单胞菌在严重烧伤患者全身感染期间在血液中适应和存活的能力知之甚少。为了确定此类适应性变化,对在一名健康志愿者或三名严重烧伤患者的全血中生长的铜绿假单胞菌菌株PA14进行了转录组分析(RNA测序)。与在健康志愿者血液中的生长情况相比,PA14在严重烧伤患者血液中的生长显著改变了2596个基因的表达,其中1060个基因的表达增强,而1536个基因的表达降低。表达显著降低的基因包括与群体感应、群体感应控制的毒力因子以及血红素、磷酸盐和膦酸盐转运相关的基因。表达显著增强的基因与III型分泌系统、绿脓菌素铁获取系统、鞭毛合成和绿脓素产生有关。我们使用qRT-PCR证实了其中许多基因表达的变化。尽管严重烧伤改变了每位患者不同血液成分的水平,但PA14在他们血液中的生长对每个基因的表达产生了相似的变化。这些结果表明,作为其生存策略的一部分,铜绿假单胞菌会响应严重烧伤患者血液中的变化,增强某些毒力基因的表达并降低其他基因的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a47/4774932/5c68778919c9/pone.0149229.g001.jpg

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