Jon Paczkowski, Ph.D.

Jon Paczkowski, Ph.D.

Microbial Signal Transduction and Cell-cell Communication
Ph.D., Cornell University
Postdoctoral training: Princeton University

Research Interests

Quorum sensing (QS) is a process of bacterial cell-cell communication that controls virulence and biofilm formation in many bacterial species, including the pathogens Pseudomonas aeruginosa and Vibrio cholerae. QS relies on the production, accumulation, detection, and population-wide response to extracellular signal molecules called autoinducers (AI). QS allows bacteria to synchronously alter gene expression patterns that underpin collective behaviors.

QS is now understood to be the norm in the bacterial world. Nonetheless, how different bacterial QS receptors selectively bind ligands to initiate signal transduction is not understood. Defining ligand-receptor interactions and how ligands are selected or rejected in QS-mediated communication will be key for generally understanding the molecular principles underlying receptor specificity and promiscuity, and specifically, the respective benefits and drawbacks of strict versus relaxed ligand detection in QS-mediated communication.

Bacteria live in heterogeneous communities and encounter mixtures of AIs produced by themselves, their kin, and their non-kin neighbors. Learning how bacteria correctly interpret these blends of AIs and elicit appropriate gene expression responses is essential to understand how bacteria communicate, and, more globally, to understand how all organisms decode environmental stimuli. QS presents a unique opportunity to understand these longstanding questions in biology.

To learn more, please visit the Paczkowski Laboratory.

Select Publications
Keegan NR, Colón Torres NJ, Stringer AM, Prager LI, Brockley MW, McManaman CL, Wade JT, Paczkowski JE. Promoter selectivity of the RhlR quorum-sensing transcription factor receptor in Pseudomonas aeruginosa is coordinated by distinct and overlapping dependencies on C4-homoserine lactone and PqsE. PLoS Genet. 2023; 19 (12): e1010900. DOI: 10.1371/journal.pgen.1010900
Simanek KA, Schumacher ML, Mallery CP, Shen S, Li L, Paczkowski JE. Quorum-sensing synthase mutations re-calibrate autoinducer concentrations in clinical isolates of Pseudomonas aeruginosa to enhance pathogenesis. Nat Commun. 2023; 14 (1): 7986. DOI: 10.1038/s41467-023-43702-4
Feathers JR, Richael EK, Simanek KA, Fromme JC, Paczkowski JE. Structure of the RhlR-PqsE complex from Pseudomonas aeruginosa reveals mechanistic insights into quorum-sensing gene regulation. Structure. 2022; 30 (12): 1626-1636. DOI: 10.1016/j.str.2022.10.008
Simanek KA, Taylor IR, Richael EK, Lasek-Nesselquist E, Bassler BL, Paczkowski JE. The PqsE-RhlR Interaction Regulates RhlR DNA Binding to Control Virulence Factor Production in Pseudomonas aeruginosa. Microbiol Spectr. 2022; 10 (1): e0210821. DOI: 10.1128/spectrum.02108-21
Paczkowski JE, McCready AR, Cong JP, Li Z, Jeffrey PD, Smith CD, Henke BR,
Hughson FM, Bassler BL. An Autoinducer Analogue Reveals an Alternative Mode of Ligand Binding for the LasR Quorum-Sensing Receptor. ACS Chem Biol. 2019 Mar; 14 (3): 378-389.
McCready AR, Paczkowski JE, Cong JP, Bassler BL. An autoinducer-independent RhlR quorum-sensing receptor enables analysis of RhlR regulation. PLoS Pathog. 2019 June; 15 (6): e1007820.
Full publication listing