Integrating proteomic data with metabolic modeling provides insight into key pathways of Bordetella pertussis
Hiroki Suyama1, Laurence Don Wai Luu1, Ling Zhong2
1School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
Abstract:
Pertussis, commonly known as whooping cough is a severe respiratory disease caused by the bacterium, Bordetella pertussis. Despite widespread vaccination, pertussis resurgence has been observed globally. The development of the current acellular vaccine (ACV) has been based on planktonic studies. However, recent studies have shown that B. pertussis readily forms biofilms. A better understanding of B. pertussis biofilms is important for developing novel vaccines that can target all aspects of B. pertussis infection. This study compared the proteomic expression of biofilm and planktonic B. pertussis cells to identify key changes between the conditions. Major differences were identified in virulence factors including an upregulation of toxins (adenylate cyclase toxin and dermonecrotic toxin) and downregulation of pertactin and type III secretion system proteins in biofilm cells. To further dissect metabolic pathways that are altered during the biofilm lifestyle, the proteomic data was then incorporated into a genome scale metabolic model using the Integrative Metabolic Analysis Tool (iMAT). The generated models predicted that planktonic cells utilised the glyoxylate shunt while biofilm cells completed the full tricarboxylic acid cycle. Differences in processing aspartate, arginine and alanine were identified as well as unique export of valine out of biofilm cells which may have a role in inter-bacterial communication and regulation. Finally, increased polyhydroxybutyrate accumulation and superoxide dismutase activity in biofilm cells may contribute to increased persistence during infection. Taken together, this study modeled major proteomic and metabolic changes that occur in biofilm cells which helps lay the groundwork for further understanding B. pertussis pathogenesis.
Insights
Whooping cough (pertussis) bacteria form biofilms, altering virulence factors and metabolism. Understanding these biofilm changes is key to developing new vaccines against persistent Bordetella pertussis infections.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Vaccine Development
Background:
- Pertussis (whooping cough), caused by *Bordetella pertussis*, is a significant respiratory illness.
- Global resurgence of pertussis occurs despite widespread vaccination.
- Current vaccines are based on planktonic bacteria, but *B. pertussis* forms biofilms.
Purpose of the Study:
- To compare proteomic and metabolic differences between biofilm and planktonic *B. pertussis*.
- To identify key changes in virulence factors and metabolic pathways during biofilm formation.
- To provide a foundation for novel vaccine strategies targeting *B. pertussis* biofilms.
Main Methods:
- Comparative proteomics of biofilm and planktonic *B. pertussis* cells.
- Genome-scale metabolic modeling using the Integrative Metabolic Analysis Tool (iMAT).
- Analysis of virulence factors, metabolic pathways, and cellular components.
Main Results:
- Biofilm cells showed altered virulence factors, including increased toxins and decreased pertactin.
- Metabolic models predicted distinct pathways: planktonic cells used the glyoxylate shunt, while biofilm cells completed the TCA cycle.
- Biofilm cells exhibited increased polyhydroxybutyrate and superoxide dismutase activity, suggesting enhanced persistence.
Conclusions:
- Significant proteomic and metabolic shifts occur in *B. pertussis* biofilms.
- These changes, including altered virulence and enhanced persistence mechanisms, are crucial for understanding pathogenesis.
- This study provides foundational insights for developing new vaccines against *B. pertussis* biofilm infections.
