Bordetella pertussis pathogenesis: current and future challenges

Key Points Bordetella pertussis , which is the causative agent of whooping cough, has re-emerged as a public health threat despite broad vaccine coverage. Re-emergence of this disease correlates with a transition from the use of whole-cell pertussis vaccines to acellular component vaccines, and the epidemiology of pertussis has shifted while the overall number of pertussis cases has increased. Bordetella spp. are paradigms for studying global virulence-control systems, bacterial toxins, type V secretion proteins and the evolution of pathogens. Bordetella spp. produce many virulence factors that contribute to pathogenesis, including toxins, adhesion factors, iron-acquisition systems and surface structures. Considering the fact that Bordetella pertussis is a strict human pathogen, the development of appropriate animal models has been challenging. However, a novel baboon infection and transmission model provides a promising new research avenue. Future goals include improving the efficacy of vaccines, protecting unvaccinated infants from infection and developing better treatment strategies for infants who become infected with B. pertussis . Achieving these goals requires a more thorough understanding of the mechanisms that are used by B. pertussis to establish infection and cause disease. The causative agent of whooping cough, Bordetella pertussis , has recently re-emerged as a serious public health concern. Here, Cotter, Miller and colleagues discuss the pathogenesis of pertussis, the shortcomings of current vaccines and the future challenges that need to be addressed for the development of more effective therapeutic strategies. Pertussis, also known as whooping cough, has recently re-emerged as a major public health threat despite high levels of vaccination against the aetiological agent Bordetella pertussis . In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into B. pertussis virulence-factor function. We also discuss the changing epidemiology of pertussis and the challenges facing vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies.