Microbial communities dramatically influence human health through causing disease, protecting against pathogens, and manipulating metabolism. It is therefore of great interest to understand the forces that shape the content and dynamics of microbial communities. Such an understanding will require an integrated approach that ties the biochemistry of microbial metabolism to ecological and evolutionary processes.
The first aim i s to utilize systems biology tools to determine the functional basis of the cooperation that evolved in a model microbial community. Increased productivity was observed in a two-species community after Salmonella enterica evolved to secrete a metabolite necessary for the growth of the Escherichia coli. Metabolomic, transcriptomic and genomic analysis of the bacteria before and after evolution will be used to determine the functional cause of the observed evolutionary change.
The second aim i s to determine the extent to which evolutionary patterns observed in two-species communities can be extrapolated to more complex communities. Methylobacterium extorquens will be grown with E. coli and Salmonella to create a community in which all three species are required for growth. It will be tested whether theory about the evolution of cooperation can still predict adaptation in this more complex assemblage. Additionally, high throughput methods will be used to test the degree to which community evolution is parallel.
The third aim i s to test the constraints on the metabolites one bacteria will evolve to provide another. A novel implementation of flux balance analysis will be used to determine the complete set of E. coli gene functions for which Salmonella can evolve to compensate. These predictions will be tested by evolving Salmonella in the presence of 10 representative E. coli knockout lines.

Public Health Relevance

Microbial communities dramatically influence human health. They make us sick, protect us from illness and determine how we metabolize the things we eat. It is therefore of great interest to understand the forces that shape the content and dynamics of microbial communities. This study investigates how evolution changes the properties of communities of bacteria.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM090760-02
Application #
8217311
Study Section
Special Emphasis Panel (ZRG1-F08-E (20))
Program Officer
Bender, Michael T
Project Start
2010-08-01
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
2
Fiscal Year
2011
Total Cost
$51,326
Indirect Cost
Name
Harvard University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Harcombe, William R; Betts, Alex; Shapiro, Jason W et al. (2016) Adding biotic complexity alters the metabolic benefits of mutualism. Evolution 70:1871-81
Harcombe, William R; Riehl, William J; Dukovski, Ilija et al. (2014) Metabolic resource allocation in individual microbes determines ecosystem interactions and spatial dynamics. Cell Rep 7:1104-15
Leiby, Nicholas; Harcombe, William R; Marx, Christopher J (2012) Multiple long-term, experimentally-evolved populations of Escherichia coli acquire dependence upon citrate as an iron chelator for optimal growth on glucose. BMC Evol Biol 12:151