The Pseudomonas Quinolone Signal (PQS) Balances Life and Death in Pseudomonas aeruginosa Populations

Abstract

When environmental conditions deteriorate and become inhospitable, generic survival strategies for populations of bacteria may be to enter a dormant state that slows down metabolism, to develop a general tolerance to hostile parameters that characterize the habitat, and to impose a regime to eliminate damaged members. Here, we provide evidence that the pseudomonas quinolone signal (PQS) mediates induction of all of these phenotypes. For individual cells, PQS, an interbacterial signaling molecule of Pseudomonas aeruginosa, has both deleterious and beneficial activities: on the one hand, it acts as a pro-oxidant and sensitizes the bacteria towards oxidative and other stresses and, on the other, it efficiently induces a protective anti-oxidative stress response. We propose that this dual function fragments populations into less and more stress tolerant members which respond differentially to developing stresses in deteriorating habitats. This suggests that a little poison may be generically beneficial to populations, in promoting survival of the fittest, and in contributing to bacterial multi-cellular behavior. It further identifies PQS as an essential mediator of the shaping of the population structure of Pseudomonas and of its response to and survival in hostile environmental conditions.

Spatially dependent alkyl quinolone signaling responses to antibiotics in Pseudomonas aeruginosa swarms

“…Although cells exposed to carbenicillin exhibit a dramatic morphology change, we found that exposure to tobramycin, but not carbenicillin, resulted in profile shifts of both PQS and AQNO families during swarming. This is in contrast to reports that have suggested a general PQS response to antimicrobials (22,26,27). Our findings are consistent with the hypothesis that AQ modulations following tobramycin exposure during pre-biofilm swarming should contribute to antibiotic tolerance (22,25,38), however, other factors must control P. aeruginosa tolerance to carbenicillin.…”

“…3A). This result agrees with prior reports that show PQS to be involved in cell death and swarm repression (22,24), and our CRM results that show the PQS subclass present at the swarm center under these conditions (Fig. S2).…”

“…Our findings reveal a role for the PQS subclass in response to tobramycin exposure, but not carbenicillin exposure. Thus, we conclude that the PQS stress response (22,27) is not a universal response mechanism to all antibiotics. Additionally, AQs belonging to the general PQS pathway appear to be under distinct regulatory control mechanisms, since modulations to the PQS and targeted AQNOs subclasses are observed to be independent of one another.…”

“…Because previous reports have shown various roles for PQS, namely as a stress response, for planktonic P. aeruginosa cells exposed to antimicrobials (22,26,(38)(39)(40), we were interested to explore how AQs mediate P. aeruginosa behavior in motile, prebiofilm swarm communities. Additionally, the CRM chemical profile of P. aeruginosa swarms provided evidence that tobramycin exposure cues aspects of PQS production or regulation that carbenicillin does not (Fig.…”

“…Of the molecules that belong to these subclasses, the roles of HHQ, PQS, and HQNO are particularly well-documented. The AQs belonging to the PQS pathway participate in processes as diverse as intercellular quorum sensing signaling, virulence regulation, biofilm development, iron chelation, antimicrobial activity, stress response, and control of cell death (15,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). In the Pseudomonas literature, AQs are generally presented to contain 7-Carbon (C7) side chains (HHQ, PQS, and HQNO), yet 9-Carbon (C9; NHQ, C9-PQS, and NQNO) and 11-Carbon (C11; UHQ, C11-PQS, and UQNO) side chain variants of these molecules are also common (16,17).…”