Bordetella parapertussis shotgun proteomic analysis reveals key aspects of the physiological response to iron starvation and potential new determinants of pathogenesis absent in Bordetella pertussis

JUAN MARCOS OVIEDO; JUAN PABLO GORGOJO; YANINA LAMBERTI; KRISTIN SURMANN; FRANK SCHMIDT; UWE VOLKER; MARIA EUGENIA RODRIGUEZ

Bruselas

Simposio; 12th International Symposium on Bordetella; 2019

International Bordetella Society

Iron starvation is a critical stress a pathogen has to overcome during infection and induces deep changes in bacterial phenotype. In this study we employed shotgun proteomics to study Bordetella parapertussis response to iron starvation. In total 1311 proteins were monitored and of those 175 showed significant changes in abundance under iron starvation compared to a non-starved control. As expected, a large number of proteins involved in iron acquisition from different sources such as siderophores and heme was found increased in abundance, namely, BrfB, BfrC, BhuR, BhuS, BhuT, exbB, exbD, and the recently described protective antigen AfuA. We also found that the lack of iron induced significant changes in metabolism, triggering a reduction in abundance of enzymes related to the Krebs cycle, amino acids biosynthesis, cytochromes, and ribosomal proteins which suggests that B. parapertussis adapts to iron starvation by decreasing the production of iron-dependent enzymes probably to redirect iron to more essential pathways. Finally, the abundance of some virulence factors was also altered under iron starvation. Worth to mention is the increased abundance of the main toxin of this pathogen, adenylate cyclase, and the decreased abundance of WbmQ (BPP0128),a protein required for O-antigen biosynthesis which led to a reduced amount of the O-antigen molecule in iron starved B. parapertussis, an observation that deserves further investigation. Additionally, since this is the first proteomic study of B. parapertussis, we also analyzed identified proteins not encoded in the genome of B. pertussis. We found proteins potentially involved in stress tolerance, intracellular survival, pathogenesis, and virulence solely present in B. parapertussis which might help to explain the differences in the pathogenesis of these closely related species and the lack of cross protection of pertussis vaccines against B. parapertussis.