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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
High Priority, Short Term Project Award (R56)
Project #
1R56AI107016-01A1
Application #
8896095
Study Section
Special Emphasis Panel (ZRG1-IDM-M (03))
Program Officer
Taylor, Christopher E,
Project Start
2014-08-01
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$373,750
Indirect Cost
$123,750
Name
Pennsylvania State University
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802
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
Hamidou Soumana, Illiassou; Linz, Bodo; Harvill, Eric T (2017) Environmental Origin of the Genus Bordetella. Front Microbiol 8:28
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
Gorgojo, Juan; Scharrig, Emilia; Gómez, Ricardo M et al. (2017) Bordetella parapertussis Circumvents Neutrophil Extracellular Bactericidal Mechanisms. PLoS One 12:e0169936
Freyberg, Zachary; Harvill, Eric T (2017) Pathogen manipulation of host metabolism: A common strategy for immune evasion. PLoS Pathog 13:e1006669
Ivanov, Yury V; Linz, Bodo; Register, Karen B et al. (2016) Identification and taxonomic characterization of Bordetella pseudohinzii sp. nov. isolated from laboratory-raised mice. Int J Syst Evol Microbiol 66:5452-5459
Linz, Bodo; Ivanov, Yury V; Preston, Andrew et al. (2016) Acquisition and loss of virulence-associated factors during genome evolution and speciation in three clades of Bordetella species. BMC Genomics 17:767
Bendor, Liron; Weyrich, Laura S; Linz, Bodo et al. (2015) Type Six Secretion System of Bordetella bronchiseptica and Adaptive Immune Components Limit Intracellular Survival During Infection. PLoS One 10:e0140743
Ivanov, Yury V; Shariat, Nikki; Register, Karen B et al. (2015) A newly discovered Bordetella species carries a transcriptionally active CRISPR-Cas with a small Cas9 endonuclease. BMC Genomics 16:863
Bolotin, Shelly; Harvill, Eric T; Crowcroft, Natasha S (2015) What to do about pertussis vaccines? Linking what we know about pertussis vaccine effectiveness, immunology and disease transmission to create a better vaccine. Pathog Dis 73:ftv057

Showing the most recent 10 out of 13 publications