AphA and LuxR/HapR reciprocally control quorum sensing in vibrios

Steven T. Rutherford¹, Julia C. van Kessel¹, Yi Shao¹,, and Bonnie L. Bassler^1,2,3

¹ Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA;
² Howard Hughes Medical Institute, Princeton University, Princeton, New Jersey 08544, USA

Abstract: Bacteria cycle between periods when they perform individual behaviors and periods when they perform group behaviors. These transitions are controlled by a cell–cell communication process called quorum sensing, in which extracellular signal molecules, called autoinducers (AIs), are released, accumulate, and are synchronously detected by a group of bacteria. AI detection results in community-wide changes in gene expression, enabling bacteria to collectively execute behaviors such as bioluminescence, biofilm formation, and virulence factor production. In this study, we show that the transcription factor AphA is a master regulator of quorum sensing that operates at low cell density (LCD) in Vibrio harveyi and Vibrio cholerae. In contrast, LuxR (V. harveyi)/HapR (V. cholerae) is the master regulator that operates at high cell density (HCD). At LCD, redundant small noncoding RNAs (sRNAs) activate production of AphA, and AphA and the sRNAs repress production of LuxR/HapR. Conversely, at HCD, LuxR/HapR represses aphA. This network architecture ensures maximal AphA production at LCD and maximal LuxR/HapR production at HCD. Microarray analyses reveal that 300 genes are regulated by AphA at LCD in V. harveyi, a subset of which is also controlled by LuxR. We propose that reciprocal gradients of AphA and LuxR/HapR establish the quorum-sensing LCD and HCD gene expression patterns, respectively.

Key Words: quorum sensing • AphA • LuxR • Qrr sRNA • virulence

Received for publication November 22, 2010. Accepted for publication January 5, 2011.

E-MAIL bbassler{at}princeton.edu; FAX (609) 258-2957.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.2015011.

Supplemental material is available for this article.

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