Human Pleural Fluid and Human Serum Albumin Modulate the Behavior of a Hypervirulent and Multidrug-Resistant (MDR)
Camila Pimentel1, Casin Le1, Marisel R Tuttobene1
1Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831-3599, USA.
Abstract:
Acinetobacter baumannii is a nosocomial pathogen capable of causing serious infections associated with high rates of morbidity and mortality. Due to its antimicrobial drug resistance profile, A. baumannii is categorized as an urgent priority pathogen by the Centers for Disease Control and Prevention in the United States and a priority group 1 critical microorganism by the World Health Organization. Understanding how A. baumannii adapts to different host environments may provide critical insights into strategically targeting this pathogen with novel antimicrobial and biological therapeutics. Exposure to human fluids was previously shown to alter the gene expression profile of a highly drug-susceptible A. baumannii strain A118 leading to persistence and survival of this pathogen. Herein, we explore the impact of human pleural fluid (HPF) and human serum albumin (HSA) on the gene expression profile of a highly multi-drug-resistant strain of A. baumannii AB5075. Differential expression was observed for ~30 genes, whose products are involved in quorum sensing, quorum quenching, iron acquisition, fatty acid metabolism, biofilm formation, secretion systems, and type IV pilus formation. Phenotypic and further transcriptomic analysis using quantitative RT-PCR confirmed RNA-seq data and demonstrated a distinctive role of HSA as the molecule involved in A. baumannii's response.
Insights
Human serum albumin (HSA) significantly alters the gene expression of the multi-drug-resistant bacterium Acinetobacter baumannii. This finding offers insights into targeting this urgent priority pathogen with new therapeutics.
Area of Science:
- Microbiology
- Genomics
- Pathogen Adaptation
Background:
- Acinetobacter baumannii is a critical nosocomial pathogen with high antimicrobial resistance.
- It is classified as an urgent priority pathogen by the CDC and WHO.
- Understanding its adaptation to host environments is key for developing new treatments.
Purpose of the Study:
- To investigate the impact of human pleural fluid (HPF) and human serum albumin (HSA) on the gene expression of multi-drug-resistant A. baumannii AB5075.
- To identify specific host molecules that trigger adaptive responses in A. baumannii.
Main Methods:
- RNA sequencing (RNA-seq) to analyze differential gene expression.
- Quantitative reverse transcription PCR (qRT-PCR) for transcriptomic validation.
- Phenotypic analysis to confirm gene expression changes.
Main Results:
- Exposure to HPF and HSA induced differential expression in approximately 30 genes.
- Affected genes are involved in quorum sensing, iron acquisition, biofilm formation, and type IV pilus.
- Human serum albumin (HSA) was identified as a key molecule driving A. baumannii's response.
Conclusions:
- Human serum albumin plays a distinctive role in modulating the gene expression of multi-drug-resistant A. baumannii.
- These findings provide insights into pathogen adaptation mechanisms.
- Targeting HSA-mediated responses could be a strategy for novel antimicrobial therapies.
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