Host immune stress reveals a role for potassium homeostasis in Pseudomonas aeruginosa aggregate stability

Pseudomonas aeruginosa (Pa) develops complex multicellular structures called aggregates during persistent lung infections. However, the exact mechanisms governing aggregate formation and dispersal are not fully understood. This study explored how Pa aggregates react to human neutrophil elastase (HNE), a host-derived enzyme that breaks down proteins, commonly found in cystic fibrosis airways.

Genetic and functional analyses revealed that the kdpFABC gene, which encodes the high-affinity potassium transport system, plays a significant role in Pa aggregate physiology. When exposed to HNE, aggregates showed strong activation of the kdpFABC system, with a stronger response in aggregate populations compared to individual cells.

Moreover, deleting the kdpA gene caused a decrease in aggregate size, a reduction in total biomass, and faster dispersal, even when HNE was not present. Restoring the kdpA gene through genetic complementation reestablished these kdpA-dependent traits, but co-culturing with normal cells could not reverse the mutant's effects. Additionally, raising the surrounding potassium concentration altered aggregate volume, biomass, and dispersal in the kdpA mutant, but did not completely restore these behaviors to normal levels, indicating that kdpA influences Pa aggregate behavior in response to potassium levels.

The results suggest that KdpA functions as a bridge between potassium homeostasis and Pa aggregate dynamics, potentially playing a role in the coordinated growth, organization, and dispersal of the bacterial population during host immune stress.