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Cerebrospinal fluid (CSF) augments metabolism and virulence expression factors in Acinetobacter baumannii
Scientific Reports ( IF 3.8 ) Pub Date : 2021-02-26 , DOI: 10.1038/s41598-021-81714-6
Jasmine Martinez 1 , Chelsea Razo-Gutierrez 1 , Casin Le 1 , Robert Courville 1 , Camila Pimentel 1 , Christine Liu 1 , Sammie E Fung 1 , Marisel R Tuttobene 1 , Kimberly Phan 1 , Alejandro J Vila 2, 3 , Parvin Shahrestani 1 , Veronica Jimenez 1 , Marcelo E Tolmasky 1 , Scott A Becka 4 , Krisztina M Papp-Wallace 4, 5, 6 , Robert A Bonomo 4, 5, 6 , Alfonso Soler-Bistue 7 , Rodrigo Sieira 8 , Maria Soledad Ramirez 1
Affiliation  

In a recent report by the Centers for Disease Control and Prevention (CDC), multidrug resistant (MDR) Acinetobacter baumannii is a pathogen described as an “urgent threat.” Infection with this bacterium manifests as different diseases such as community and nosocomial pneumonia, bloodstream infections, endocarditis, infections of the urinary tract, wound infections, burn infections, skin and soft tissue infections, and meningitis. In particular, nosocomial meningitis, an unwelcome complication of neurosurgery caused by extensively-drug resistant (XDR) A. baumannii, is extremely challenging to manage. Therefore, understanding how A. baumannii adapts to different host environments, such as cerebrospinal fluid (CSF) that may trigger changes in expression of virulence factors that are associated with the successful establishment and progress of this infection is necessary. The present in-vitro work describes, the genetic changes that occur during A. baumannii infiltration into CSF and displays A. baumannii’s expansive versatility to persist in a nutrient limited environment while enhancing several virulence factors to survive and persist. While a hypervirulent A. baumannii strain did not show changes in its transcriptome when incubated in the presence of CSF, a low-virulence isolate showed significant differences in gene expression and phenotypic traits. Exposure to 4% CSF caused increased expression of virulence factors such as fimbriae, pilins, and iron chelators, and other virulence determinants that was confirmed in various model systems. Furthermore, although CSF's presence did not enhance bacterial growth, an increase of expression of genes encoding transcription, translation, and the ATP synthesis machinery was observed. This work also explores A. baumannii’s response to an essential component, human serum albumin (HSA), within CSF to trigger the differential expression of genes associated with its pathoadaptibility in this environment.



中文翻译:


脑脊液 (CSF) 增强鲍曼不动杆菌的代谢和毒力表达因子



在美国疾病控制与预防中心 (CDC) 最近的一份报告中,多重耐药 (MDR)鲍曼不动杆菌是一种被描述为“紧急威胁”的病原体。这种细菌的感染表现为不同的疾病,如社区和医院肺炎、血流感染、心内膜炎、尿路感染、伤口感染、烧伤感染、皮肤和软组织感染以及脑膜炎。特别是,院内脑膜炎是一种由广泛耐药 (XDR)鲍曼不动杆菌引起的神经外科并发症,治疗起来极具挑战性。因此,了解鲍曼不动杆菌如何适应不同的宿主环境,例如脑脊液(CSF),可能会引发与这种感染的成功建立和进展相关的毒力因子表达的变化。目前的体外工作描述了鲍曼不动杆菌渗入脑脊液期间发生的遗传变化,并显示了鲍曼不动杆菌在营养有限的环境中持续存在的广泛多功能性,同时增强了多种毒力因子的生存和持续存在。虽然高毒力鲍曼不动杆菌菌株在脑脊液存在下孵育时其转录组没有表现出变化,但低毒力分离株在基因表达和表型性状方面显示出显着差异。暴露于 4% CSF 会导致菌毛、菌毛蛋白和铁螯合剂等毒力因子以及其他毒力决定因素的表达增加,这在各种模型系统中得到了证实。 此外,虽然CSF的存在并没有促进细菌生长,但观察到编码转录、翻译和ATP合成机制的基因表达增加。这项工作还探讨了鲍曼不动杆菌对脑脊液中一种重要成分人血清白蛋白 (HSA) 的反应,以触发与其在此环境中的病理适应性相关的基因的差异表达。

更新日期:2021-02-26
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