Many animal and plant diseases, such as the human diseases cholera, typhoid fever, and legionelliosis, are caused by facultative bacterial pathogens, that exist and proliferate outside the host environment. While the epidemiology of obligate pathogens is well described by established population models of disease, these models are inadequate for facultative bacterial pathogens, and do not incorporate several important features of their biology. The frequency of virulent strains, for example, is strongly affected by local scale competition, both within the host, where virulent strains have a competitive advantage, and outside the host, where the cost of virulence is expected to be disadvantageous. Moreover, virulence genes are often encoded on mobile elements such as plasmids, allowing their spread among bacteria through horizontal gene transfer. In this proposal, modeling and empirical approaches are combined to investigate the influence of local scale competition and horizontal gene transfer on virulence dynamics, and the maintenance of virulence, for facultative bacterial pathogens. General models will be developed, parameterized and tested using Agrobacterium tumefaciens, an easily manipulated and ubiquitous facultative plant pathogen. A. tumefaciens causes crown gall disease, and is a model for pathogenesis mechanisms and horizontal gene transfer. Construction of isogenic lines with defined mutations, will allow unambiguous evaluation of the costs and competitive advantages conferred by virulence and conjugation. Moreover, several defining aspects of the ^. tumefaciens disease environment, such as plant-released inducers of virulence and production of customized nutrients, called opines, by infected plants, can be readily simulated in the laboratory. Conditions that should favor virulent strains or avirulent strains (nonpathogens and cheaters), will be tested for the predicted interactions. The effects of resource competition will be evaluated in the diseased host and non-host environments, performing experiments in vitro, in vivo, and the field. These results then form the basis for evaluating the importance of horizontal gene transfer of virulence genes and for scaling up to infection dynamics and disease incidence.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM092660-04
Application #
8434184
Study Section
Special Emphasis Panel (ZRG1-BDA-K (51))
Program Officer
Eckstrand, Irene A
Project Start
2010-03-15
Project End
2014-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
4
Fiscal Year
2013
Total Cost
$189,361
Indirect Cost
$66,399
Name
Indiana University Bloomington
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
Steidinger, Brian S; Bever, James D (2014) The coexistence of hosts with different abilities to discriminate against cheater partners: an evolutionary game-theory approach. Am Nat 183:762-70
Zee, Peter C; Bever, James D (2014) Joint evolution of kin recognition and cooperation in spatially structured rhizobium populations. PLoS One 9:e95141
Morton, Elise R; Platt, Thomas G; Fuqua, Clay et al. (2014) Non-additive costs and interactions alter the competitive dynamics of co-occurring ecologically distinct plasmids. Proc Biol Sci 281:20132173
Larimer, Anna L; Clay, Keith; Bever, James D (2014) Synergism and context dependency of interactions between arbuscular mycorrhizal fungi and rhizobia with a prairie legume. Ecology 95:1045-54
Mack, Keenan M L; Bever, James D (2014) Coexistence and relative abundance in plant communities are determined by feedbacks when the scale of feedback and dispersal is local. J Ecol 102:1195-1201
Venturi, Vittorio; Fuqua, Clay (2013) Chemical signaling between plants and plant-pathogenic bacteria. Annu Rev Phytopathol 51:17-37
Morton, Elise R; Merritt, Peter M; Bever, James D et al. (2013) Large deletions in the pAtC58 megaplasmid of Agrobacterium tumefaciens can confer reduced carriage cost and increased expression of virulence genes. Genome Biol Evol 5:1353-64
Bever, James D; Broadhurst, Linda M; Thrall, Peter H (2013) Microbial phylotype composition and diversity predicts plant productivity and plant-soil feedbacks. Ecol Lett 16:167-74
Xu, Jing; Platt, Thomas G; Fuqua, Clay (2012) Regulatory linkages between flagella and surfactant during swarming behavior: lubricating the flagellar propeller? J Bacteriol 194:1283-6
Platt, Thomas G; Bever, James D; Fuqua, Clay (2012) A cooperative virulence plasmid imposes a high fitness cost under conditions that induce pathogenesis. Proc Biol Sci 279:1691-9

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