The accelerating emergence of antibiotics resistant bacteria has become a global health crisis, costing tens of thousands of lives and hundreds of billions of dollars every year. Horizontal transfer of antibiotics resistance genes (ARGs) is a key mechanism driving the emergence of antibiotic resistant strains, but the ecological processes impacting the transmission of these genes through microbial communities are largely unknown. To address this knowledge gap, we propose to develop an ultrahigh-throughput single cell sequencing technology to identify the associations between ARGs and microbial taxa. This method will be used to decipher the time- dependent horizontal gene transfer networks underlying ARG spread in a human gut microbiome in response to clinically relevant antibiotics. The new technology will enable single cell analysis of microbial communities at an unprecedented scale. Deciphering the horizontal gene transfer networks responsible for ARG dissemination will deepen our understanding of the ecological interactions involved in the emergence of antibiotic resistant bacteria and inform the design of interventions to substantially reduce ARG propagation. A detailed understanding of the environmental and ecological factors influencing horizontal gene transfer is critical to combating infectious diseases.

Public Health Relevance

The emergence of antibiotic resistance bacteria that lead to infections has accelerated in recent years and is an imminent threat to global public health. The use of antibiotics is implicated in the rapid spread of antibiotic resistance, but the abiotic and biotic factors impacting these processes in microbial communities are largely unknown. To address this gap, we aim to develop a novel technology for tracking antibiotic resistance genes in complex microbial communities and apply this method to determine the mechanisms driving the spread of antibiotic resistance in a model humanized gut microbiome.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI156438-01
Application #
10108008
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Huntley, Clayton C
Project Start
2021-03-02
Project End
2023-02-28
Budget Start
2021-03-02
Budget End
2022-02-28
Support Year
1
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Biochemistry
Type
Earth Sciences/Resources
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715