- Many bacteria possess cell density-dependent quorum-sensing (QS) systems that often regulate cooperative secretions involved
in host-microbe or microbe-microbe interactions. These secretions, or “public goods,” are frequently coregulated by stress and
starvation responses. Here we provide a physiological rationale for such regulatory complexity in the opportunistic pathogen
Pseudomonas aeruginosa. Using minimal-medium batch and chemostat cultures, we comprehensively characterized specific
growth rate-limiting macronutrients as key triggers for the expression of extracellular enzymes and metabolites directly controlled
by the las and rhl QS systems. Expression was unrelated to cell density, depended on the secreted product’s elemental
composition, and was induced only when the limiting nutrient was not also a building block of the product; rhl-dependent products
showed the strongest response, caused by the largely las-independent induction of the regulator RhlR and its cognate signal.
In agreement with the prominent role of the rhl system, slow growth inverted the las-to-rhl signal ratio, previously considered a
characteristic distinguishing between planktonic and biofilm lifestyles. Our results highlight a supply-driven, metabolically prudent
regulation of public goods that minimizes production costs and thereby helps stabilize cooperative behavior. Such regulation
would be beneficial for QS-dependent public goods that act broadly and nonspecifically, and whose need cannot always be
accurately assessed by the producing cell. Clear differences in the capacities of the las and rhl systems to integrate starvation signals
help explain the existence of multiple QS systems in one cell.