Most bacterial pathogenesis studies have focused on mono-culture infections; however it is clear that many bacterial infections are not simply the result of colonization with a single species, but rather ensue from the action of polymicrobial communities. Microbes within polymicrobial infections often display synergistic interactions that result in enhanced colonization and persistence in the infection site. Such interactions have been particularly noted in wound infections, although the molecular processes controlling these synergistic interactions are generally not known. Detailed mechanistic studies of the polymicrobial interactions required for enhanced persistence in vivo are a necessary first step towards developing therapeutics to treat polymicrobial infections. The overall goal of this research plan is to determine how interactions between Pseudomonas aeruginosa and other microbes that commonly co-infect wounds impact wound severity. To accomplish this goal, in vivo murine wound models and high-throughput genomics techniques will be employed to identify and characterize microbial genes required for enhanced pathogenesis during co-infection.

Public Health Relevance

Most bacterial infections are initiated by complex multi-species communities whose members work together to enhance disease symptoms, a phenomenon known as polymicrobial synergy. The objective of this research application is to provide novel insights into the mechanisms controlling synergy in the common human wound pathogen Pseudomonas aeruginosa during co-infection with other microbes. The ultimate goal of this research is to develop novel therapeutic strategies for treating polymicrobial infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM116547-01A1
Application #
9056049
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Somers, Scott D
Project Start
2016-01-01
Project End
2019-12-31
Budget Start
2016-01-01
Budget End
2016-12-31
Support Year
1
Fiscal Year
2016
Total Cost
$316,335
Indirect Cost
$66,335
Name
University of Texas Austin
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
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Smith, Allie Clinton; Rice, Anne; Sutton, Bryan et al. (2017) Albumin Inhibits Pseudomonas aeruginosa Quorum Sensing and Alters Polymicrobial Interactions. Infect Immun 85:
Sønderholm, Majken; Kragh, Kasper Nørskov; Koren, Klaus et al. (2017) Pseudomonas aeruginosa Aggregate Formation in an Alginate Bead Model System Exhibits In Vivo-Like Characteristics. Appl Environ Microbiol 83:
Everett, Jake; Turner, Keith; Cai, Qiuxian et al. (2017) Arginine Is a Critical Substrate for the Pathogenesis of Pseudomonas aeruginosa in Burn Wound Infections. MBio 8:
Darch, Sophie E; Kragh, Kasper N; Abbott, Evelyn A et al. (2017) Phage Inhibit Pathogen Dissemination by Targeting Bacterial Migrants in a Chronic Infection Model. MBio 8:
Kragh, Kasper Nørskov; Alhede, Maria; Rybtke, Morten et al. (2017) Inoculation method could impact the outcome of microbiological experiments. Appl Environ Microbiol :

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