The hierarchy quorum sensing network in Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa causes severe and persistent infections in immune compromised individuals and cystic fibrosis sufferers. The infection is hard to eradicate as P. aeruginosa has developed strong resistance to most conventional antibiotics. The problem is further compounded by the ability of the pathogen to form biofilm matrix, which provides bacterial cells a protected environment withstanding various stresses including antibiotics. Quorum sensing (QS), a cell density-based intercellular communication system, which plays a key role in regulation of the bacterial virulence and biofilm formation, could be a promising target for developing new strategies against P. aeruginosa infection. The QS network of P. aeruginosa is organized in a multi-layered hierarchy consisting of at least four interconnected signaling mechanisms. Evidence is accumulating that the QS regulatory network not only responds to bacterial population changes but also could react to environmental stress cues. This plasticity should be taken into consideration during exploration and development of anti-QS therapeutics.

Figure 1

Virulence mechanisms employed during P. aeruginosa infections

Figure 2

Structures ofP. aeruginosaquorum sensing (QS) signals. Clockwise from left, N-(3-oxododecanoyl)-homoserine lactone (OdDHL); N-butyrylhomoserine lactone (BHL); 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas Quinolone Signal, PQS); 2-(2-hydroxyphenyl)-thiazole-4-carbaldehyde (Integrated Quorum Sensing Signal, IQS)

Figure 3

Schematic representation of the four QS signaling networks inP. aeruginosaand their respective regulons. Arrows indicate a stimulatory effect. Perpendicular lines indicate an inhibitory effect

Figure 4

Schematic representation of how environmental conditions and host factors influence theP. aeruginosaQS signaling hierarchy. For simplicity, the QS systems are represented as a whole unit, namely, las, iqs, pqs and rhl