Although the interactions between invading pathogens and the host's resident microbiota are clearly important to the outcome of many infections, they remain poorly understood with few experimental systems in which they can be explored at a molecular mechanistic level. We have recently identified striking differences between closely related pathogens of the genus Bordetella in their interactions with host microbiome that can explain important aspects of their biology, including host specificity and pathology. B. bronchiseptica efficiently colonizes the upper respiratory tracts (URT) of mice (ID50<10cfu) and displaces the resident microflora in the process. B. pertussis, which causes highly contagious Whooping Cough in humans, poorly colonizes mice (ID50>1000cfu) and does not affect resident microbiota. Testing the hypothesis that resident microbiota of mice inhibit colonization, we observed that clearing the URT of bacteria allows B. pertussis to efficiently colonize (ID50<100). We have now extended this work by identifying specific microorganisms that can prevent B. pertussis colonization. This application will 1. Define the ability of resident microorganism(s) to inhibit B. pertussis colonization of mice, 2. Identify ecological mechanisms of competition amongst nasal microbiota and invading bordetellae, and 3. Determine the molecular mechanisms by which B. bronchiseptica clears microflora from the URT. This exceptionally powerful and tractable experimental system will allow us to study the complex interactions between invading pathogen and host resident microbiota to satisfying molecular mechanisms. Improved understanding of these interactions is likely to inform views of the many other mucosal pathogens for which there is not such a powerful host infection experimental system.

Public Health Relevance

There is growing appreciation that the host microbiome can have profound effects on health and susceptibility to disease, but few model systems in which to study the details of interactions between invading pathogens and resident microbiota. We have recently shown that Bordetella pertussis, which causes whooping cough in humans, poorly colonizes the respiratory tracts of mice because of competition with resident microflora, while the closely related B. bronchiseptica is able to efficiently colonize mice, displacing the resident microflora in the process. This application seeks to understand the ecological mechanisms behind how resident microorganisms inhibit B. pertussis colonization and the molecular mechanisms by which B. bronchiseptica eliminates them.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
High Priority, Short Term Project Award (R56)
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Special Emphasis Panel (ZRG1-IDM-M (03))
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Taylor, Christopher E,
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Pennsylvania State University
Veterinary Sciences
Schools of Earth Sciences/Natur
University Park
United States
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Gestal, Monica C; Rivera, Israel; Howard, Laura K et al. (2018) Blood or Serum Exposure Induce Global Transcriptional Changes, Altered Antigenic Profile, and Increased Cytotoxicity by Classical Bordetellae. Front Microbiol 9:1969
Taylor-Mulneix, Dawn L; Bendor, Liron; Linz, Bodo et al. (2017) Bordetella bronchiseptica exploits the complex life cycle of Dictyostelium discoideum as an amplifying transmission vector. PLoS Biol 15:e2000420
Taylor-Mulneix, Dawn L; Hamidou Soumana, Illiassou; Linz, Bodo et al. (2017) Evolution of Bordetellae from Environmental Microbes to Human Respiratory Pathogens: Amoebae as a Missing Link. Front Cell Infect Microbiol 7:510
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