Quorum sensing is a form of cell-cell communication that allows members of a population to coordinate activities in a cell density-dependent fashion. Quorum sensing has been shown to play a significant role in the virulence of Pseudomonas aeruginosa and other pathogens. This research program is focused on P. aeruginosa, which controls a battery of virulence factors by acyl-homoserine lactone quorum sensing. We have been and will continue to be interested in basic mechanisms of quorum sensing, and the selective pressures favoring quorum sensing control of gene expression and the costs and benefits of quorum sensing in P. aeruginosa. It is thought that quorum sensing functions to control and coordinate cooperative behaviors, a generally accepted view that is supported by limited experimental evidence. It is clear that cooperativity is an evolved biological phenomenon, but there is considerable controversy about the selective forces leading to cooperativity, what are the costs and benefits of cooperativity, and what are the possible advantages to controlling cooperativity by quorum sensing. We will use molecular genetic approaches to begin to address the costs and benefits of controlling cooperative behavior by quorum sensing. Specifically, we aim to understand why growth on transported solutes is (infrequently) linked to quorum sensing. We will investigate molecular policing mechanisms that can punish quorum-sensing signal receptor mutants (mutants that do not produce any quorum-regulated public or shared resources). We will uncouple activation of the quorum regulon, or specific quorum-controlled factors from acyl-HSL signaling, and use our uncoupled mutants in binary culture experiments with parent strains to measure the costs and benefits of controlling the regulon or elastase by quorum sensing. The proposed experiments will provide us with experimental data critical for understanding the relationship between intercellular communication and cooperativity. We will examine the quorum-regulated transcriptomes and metabolomes of P. aeruginosa isolates from different environments. Our hypothesis is that the regulons will reflect the ecology of the isolate.
Pseudomonas aeruginosa is an opportunistic human pathogen that causes a variety of difficult or impossible to resolve infections. Because quorum sensing controls virulence in P. aeruginosa it has become a target for development of novel antimicrobials. Efforts to develop quorum sensing inhibitors as therapeutics will rely on a better understanding of the role of quorum sensing in virulence and on a basic understanding of the selective pressures leading to quorum sensing control of gene expression in P. aeruginosa. Quorum sensing research also affords us a window into the social behavior of bacteria at a molecular level.
|Majerczyk, Charlotte; Schneider, Emily; Greenberg, E Peter (2016) Quorum sensing control of Type VI secretion factors restricts the proliferation of quorum-sensing mutants. Elife 5:|
|Feltner, John B; Wolter, Daniel J; Pope, Christopher E et al. (2016) LasR Variant Cystic Fibrosis Isolates Reveal an Adaptable Quorum-Sensing Hierarchy in Pseudomonas aeruginosa. MBio 7:|
|Tseng, Boo Shan; Majerczyk, Charlotte D; Passos da Silva, Daniel et al. (2016) Quorum Sensing Influences Burkholderia thailandensis Biofilm Development and Matrix Production. J Bacteriol 198:2643-50|
|Wang, Meizhen; Schaefer, Amy L; Dandekar, Ajai A et al. (2015) Quorum sensing and policing of Pseudomonas aeruginosa social cheaters. Proc Natl Acad Sci U S A 112:2187-91|
|Amunts, Alexey; Fiedorczuk, Karol; Truong, Thao T et al. (2015) Bactobolin A binds to a site on the 70S ribosome distinct from previously seen antibiotics. J Mol Biol 427:753-5|
|Truong, Thao T; Seyedsayamdost, Mohammad; Greenberg, E Peter et al. (2015) A Burkholderia thailandensis Acyl-Homoserine Lactone-Independent Orphan LuxR Homolog That Activates Production of the Cytotoxin Malleilactone. J Bacteriol 197:3456-62|
|Scholz, Rebecca L; Greenberg, E Peter (2015) Sociality in Escherichia coli: Enterochelin Is a Private Good at Low Cell Density and Can Be Shared at High Cell Density. J Bacteriol 197:2122-8|
|Penterman, Jon; Nguyen, Dao; Anderson, Erin et al. (2014) Rapid evolution of culture-impaired bacteria during adaptation to biofilm growth. Cell Rep 6:293-300|
|Chugani, Sudha; Greenberg, Everett P (2014) An evolving perspective on the Pseudomonas aeruginosa orphan quorum sensing regulator QscR. Front Cell Infect Microbiol 4:152|
|Majerczyk, Charlotte D; Brittnacher, Mitchell J; Jacobs, Michael A et al. (2014) Cross-species comparison of the Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei quorum-sensing regulons. J Bacteriol 196:3862-71|
Showing the most recent 10 out of 45 publications