Plasmids play a central role in the spread of antibiotic resistance among bacterial species, thereby decreasing the effectiveness of various chemotherapeutic agents for the treatment of infectious diseases. These mobile genetic elements are very common in bacteria and their horizontal transfer is key in the adaptive evolution of these organisms. The long-term goal of this study is to understand the population biology of transmissible plasmids in spatially structured microbial communities: What are the mechanisms that drive the horizontal transfer and persistence of these mobile genetic elements? Why do they persist, even in the absence of selection for any of the genes they carry? How does the spatial structure of natural microbial communities influence the ecological and evolutionary dynamics of plasmid-bacteria interactions? Therefore, a joint theoretical and experimental investigation into the role of spatial structure in the spread and persistence of self-transmissible antibiotic resistance plasmids is proposed.
The specific aims of this proposal are to construct 2-dimensional and 3-dimensional stochastic cellular automata (CA) models that can be used to accurately predict the spread and persistence of natural antibiotic resistance plasmids in bacterial colonies growing on agar surfaces and in biofilms. These two settings are needed for carefully controlled comparisons with non-spatial (liquid) environments and estimation of spatially relevant parameters, and for understanding the extent to which the complex spatially heterogeneous structure of biofilms further influences plasmid transfer and persistence. To validate and/or modify the models, a sequence of parallel in vitro and in silico experiments will be performed. Each such pair of experiments will serve to (a) validate or reject the particular model as pertains to a specific biological hypothesis; (b) suggest model refinements; (c) test the biological hypothesis; and (d) formulate alternative hypotheses in the event that the original hypothesis is rejected.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM073821-03
Application #
7214824
Study Section
Special Emphasis Panel (ZRG1-GVE (01))
Program Officer
Eckstrand, Irene A
Project Start
2005-04-01
Project End
2010-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$242,153
Indirect Cost
Name
University of Idaho
Department
Biostatistics & Other Math Sci
Type
Schools of Arts and Sciences
DUNS #
075746271
City
Moscow
State
ID
Country
United States
Zip Code
83844
Krol, Jaroslaw E; Wojtowicz, Andrzej J; Rogers, Linda M et al. (2013) Invasion of E. coli biofilms by antibiotic resistance plasmids. Plasmid 70:110-9
Król, J E; Penrod, J T; McCaslin, H et al. (2012) Role of IncP-1? plasmids pWDL7::rfp and pNB8c in chloroaniline catabolism as determined by genomic and functional analyses. Appl Environ Microbiol 78:828-38
Zhong, Xue; Droesch, Jason; Fox, Randal et al. (2012) On the meaning and estimation of plasmid transfer rates for surface-associated and well-mixed bacterial populations. J Theor Biol 294:144-52
Król, Jaroslaw E; Nguyen, Hung Duc; Rogers, Linda M et al. (2011) Increased transfer of a multidrug resistance plasmid in Escherichia coli biofilms at the air-liquid interface. Appl Environ Microbiol 77:5079-88
Zhong, Xue; Krol, Jaros?aw E; Top, Eva M et al. (2010) Accounting for mating pair formation in plasmid population dynamics. J Theor Biol 262:711-9
Król, Jaroslaw E; Rogers, Linda M; Krone, Stephen M et al. (2010) Dual reporter system for in situ detection of plasmid transfer under aerobic and anaerobic conditions. Appl Environ Microbiol 76:4553-6
Fox, Randal E; Zhong, Xue; Krone, Stephen M et al. (2008) Spatial structure and nutrients promote invasion of IncP-1 plasmids in bacterial populations. ISME J 2:1024-39
Suzuki, Haruo; Brown, Celeste J; Forney, Larry J et al. (2008) Comparison of correspondence analysis methods for synonymous codon usage in bacteria. DNA Res 15:357-65
Krone, Stephen M; Lu, Ruinan; Fox, Randal et al. (2007) Modelling the spatial dynamics of plasmid transfer and persistence. Microbiology 153:2803-16
Schluter, Andreas; Szczepanowski, Rafael; Puhler, Alfred et al. (2007) Genomics of IncP-1 antibiotic resistance plasmids isolated from wastewater treatment plants provides evidence for a widely accessible drug resistance gene pool. FEMS Microbiol Rev 31:449-77

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