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Cerebrospinal fluid (CSF) augments metabolism and virulence expression factors in Acinetobacter baumannii
Jasmine Martinez1, Chelsea Razo-Gutierrez1, Casin Le1
1Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, 800 N State College Blvd, Fullerton, CA, 92831, USA.
Abstract:
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.
Insights
Multidrug-resistant Acinetobacter baumannii adapts to cerebrospinal fluid by increasing virulence factors, despite limited nutrients. A low-virulence strain showed significant gene expression changes, enhancing survival mechanisms.
Area of Science:
- Microbiology
- Infectious Diseases
- Genetics
Background:
- Multidrug-resistant (MDR) Acinetobacter baumannii is an urgent threat pathogen.
- Nosocomial meningitis caused by extensively-drug resistant (XDR) A. baumannii is a challenging complication of neurosurgery.
- Understanding A. baumannii adaptation to host environments like cerebrospinal fluid (CSF) is crucial for managing infections.
Purpose of the Study:
- To investigate the genetic and phenotypic changes in A. baumannii when exposed to CSF.
- To understand the bacterium's adaptability and virulence factor expression in a nutrient-limited environment.
- To explore the role of human serum albumin (HSA) in A. baumannii's response to CSF.
Main Methods:
- In vitro incubation of A. baumannii strains with CSF.
- Transcriptome analysis to assess gene expression changes.
- Phenotypic analysis to confirm changes in virulence factors.
- Investigation of bacterial response to human serum albumin (HSA) in CSF.
Main Results:
- A low-virulence A. baumannii isolate showed significant transcriptome and phenotypic changes upon CSF exposure.
- Increased expression of virulence factors like fimbriae, pilins, and iron chelators was observed.
- CSF exposure did not enhance bacterial growth but increased expression of genes for transcription, translation, and ATP synthesis.
- A. baumannii demonstrated differential gene expression in response to HSA in CSF, indicating pathoadaptability.
Conclusions:
- A. baumannii exhibits significant adaptability to the CSF environment, particularly in low-virulence strains.
- The bacterium enhances virulence factor expression and essential cellular machinery for survival and persistence in CSF.
- These findings highlight A. baumannii's capacity to adapt and cause severe infections, including meningitis, necessitating further research into therapeutic strategies.
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