Integrating proteomic data with metabolic modeling provides insight into key pathways of Bordetella pertussis biofilms

Hiroki Suyama; Laurence Don Wai Luu; Ling Zhong; Mark J Raftery; Ruiting Lan

doi:10.3389/fmicb.2023.1169870

Integrating proteomic data with metabolic modeling provides insight into key pathways of Bordetella pertussis biofilms

Front Microbiol. 2023 Aug 3:14:1169870. doi: 10.3389/fmicb.2023.1169870. eCollection 2023.

Authors

Hiroki Suyama¹, Laurence Don Wai Luu¹, Ling Zhong², Mark J Raftery², Ruiting Lan¹

Affiliations

¹ School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
² Bioanalytical Mass Spectrometry Facility, 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.

Keywords: Bordetella pertussis; infectious disease; label free quantification (LFQ); mass spectrometry; metabolic model; proteomics; whooping cough.