Integrating proteomic data with metabolic modelling provides insight into key pathways ofBordetella pertussisbiofilms

Abstract

AbstractPertussis, 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 thatB. pertussisreadily forms biofilms. A better understanding ofB. pertussisbiofilms is important for developing novel vaccines that can target all aspects ofB. pertussisinfection. This study compared the proteomic expression of biofilm and planktonicB. pertussiscells 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 analysis revealed 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 modelled major proteomic and metabolic changes that occur in biofilm cells which helps lay the groundwork for further understandingB. pertussispathogenesis.