4.7 Article

Cerebrospinal fluid (CSF) augments metabolism and virulence expression factors in Acinetobacter baumannii

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SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-021-81714-6

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  1. NIH [SC3GM125556, 2R15AI047115, R01AI100560, R01AI063517, R01AI072219]
  2. Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT)
  3. Cleveland Department of Veterans Affairs, VA Merit Review from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development [1I01BX001974, 1I01 BX002872]
  4. Geriatric Research Education and Clinical Center VISN 10

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This study investigates the genetic changes and virulence factor expression of Acinetobacter baumannii in the cerebrospinal fluid (CSF) environment, showing its adaptability and survival capabilities. While a highly virulent strain showed no transcriptome changes in the presence of CSF, a low-virulence isolate exhibited significant differences in gene expression. Exposure to CSF induced increased expression of virulence factors without promoting bacterial growth, but rather increasing the expression of genes associated with transcription, translation, and ATP synthesis.
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.

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