Bordetella pertussis is the causative agent of whooping cough, a disease that affects 20-40 million people each year, and that is increasingly prevalent in the United States. B. pertussis responds to environmental changes in the host airway by coordinately regulating the transcription of virulence factors, suggesting that virulence factor expression in vivo can be temporally and spatially restricted, thereby enabling efficient colonization and persistence of the pathogen. Our current understanding of relevant environmental cues and their corresponding B. pertussis gene expression responses is incomplete. The long-term objectives of this project are (1) to identify the environmental cues and signaling molecules in the human airway that influence B. pertussis gene expression and (2) to describe, at the genomic level, these B. pertussis transcriptional responses. Specifically, this proposal aims to 1) define B. pertussis transcriptional responses to components of the host environment including low concentrations of iron and amino acids, and presence of mucin, 2) measure B. pertussis global gene expression during host airway cell contact and intimate adherence, and 3) determine effects of growth phase and cell density on B. pertussis gene expression. These questions will be addressed at the genome level using a recently developed B. pertussis DNA microarray to simultaneously measure expression of almost every putative open reading frame. The knowledge gained from this study will lead to a detailed molecular understanding of B. pertussis virulence mechanisms and physiological adaptations, as well as the complex interplay between this pathogen and the human host, which could, in turn, lead to the development of novel pertussis vaccines and therapeutics. ? ?
