A balancing act: investigations on the impact of altered signal sensitivity in bacterial quorum sensing

Abstract

ABSTRACT Many bacterial species communicate and cooperate with kin using a form of cell-cell signaling called quorum sensing. Sensitivity and selectivity are fundamental properties of quorum sensing, and of cell signaling more generally, as they dictate the ability of cells to accurately detect and interpret signals. In this study, we investigate the impact of signal sensitivity on gene regulation and on bacterial fitness using two variants of the LasR quorum sensing receptor in the opportunistic pathogen Pseudomonas aeruginosa . Our studies reinforce that altering LasR signal-binding residues tends to result in decreased signal selectivity. We also find that LasR hyper-sensitivity results in earlier and stronger expression of LasR-regulated genes, whereas hypo-sensitivity results in delayed transcription from both LasR- and RhlR-regulated promoters. Furthermore, strains expressing either the hyper- or hypo-sensitive LasR polypeptide exhibit reduced production of pyocyanin, a key antimicrobial that impacts intra- and interspecies competition as well as pathogenicity. These changes to gene expression underscore the complex regulatory network by which P. aeruginosa controls group behaviors. Ultimately, altered signal sensitivity results in a fitness defect for LasR hyper-sensitive cells during kin competition against wild-type P. aeruginosa and for hypo-sensitive cells during interspecies competition against the opportunistic pathogen Burkholderia multivorans . Our findings highlight the delicate balance between group behaviors regulated by quorum sensing and bacterial fitness and contribute to a better understanding of the evolutionary pressures that may tune sensitivity in cell-cell signaling. IMPORTANCE Quorum sensing (QS) is a widespread form of cell-cell signaling that regulates group behaviors important for competition and cooperation within bacterial communities. The QS systems from different bacterial species have diverse properties, but the functional consequences of this diversity are largely unknown. Taking advantage of hyper- and hypo-sensitive QS receptor variants in the opportunistic pathogen Pseudomonas aeruginosa , we examine the costs and benefits of altered signal sensitivity. We find that the sensitivity of a model QS receptor, LasR, impacts the timing and level of quorum gene expression, and fitness during intra- and interspecies competition. These findings suggest competition with kin and with other bacterial species work together to tune signal sensitivity.