PT  - JOURNAL ARTICLE
AU  - A. Ruparell
AU  - JF. Dubern
AU  - CA. Ortori
AU  - F. Harrison
AU  - NM. Halliday
AU  - A. Emtage
AU  - M. Ashawesh
AU  - CA. Laughton
AU  - SP. Diggle
AU  - P. Williams
AU  - DA. Barrett
AU  - KR. Hardie
TI  - The fitness burden imposed by synthesising quorum sensing signals
AID  - 10.1101/050229
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 050229
4099  - http://biorxiv.org/content/early/2016/04/26/050229.short
4100  - http://biorxiv.org/content/early/2016/04/26/050229.full
AB  - It is now well established that bacterial populations utilize cell-to-cell signaling (quorum-sensing, QS) to control the production of public goods and other co-operative behaviours. Evolutionary theory predicts that both the cost of signal production and the response to signals should incur fitness costs for producing cells. Although costs imposed by the downstream consequences of QS have been shown, it has not been demonstrated that the production of QS signal molecules (QSSMs) results in a decrease in fitness. We measured the fitness cost to cells of synthesising QSSMs by quantifying metabolite levels in the presence of QSSM synthases. We found that: (i) bacteria making QSSMs have a growth defect that exerts an evolutionary cost, (ii) production of QSSMs correlates with reduced intracellular concentrations of QSSM precursors, (iii) the production of heterologous QSSMs negatively impacts the production of a native QSSM that shares common substrates, and (iv) supplementation with exogenously added metabolites partially rescued growth defects imposed by QSSM synthesis. These data provide the first direct experimental evidence that the production of QS signals carries fitness costs to producer cells.Originality-Significance Statement Bacterial cells within populations communicate with each other to control social behaviors by producing diffusible quorum sensing (QS) signal molecules. Evolutionary theory predicts that both the cost of signal production and the response to signals should incur fitness costs for producing cells. Here we provide the first empirical evidence that the production of QS signals incurs fitness costs to producing cells. Since QS plays a major role in bacterial pathogenicity, this finding will underpin novel antimicrobial strategies that are urgently needed to replace currently available antimicrobials that are becoming obsolete through the ever-rising incidence of resistance.