P. aeruginosa infects a broad spectrum of hosts, ranging from plants and protozoa over fish and invertebrates to mammals and humans. The versatility of the pathogen is reflected by one of the largest bacterial genomes sequenced so far as well as by its extraordinary panel of virulence factors. So, P. aeruginosa expresses a limited number of polar pili, which are involved in attachment to eukaryotic cells. Furthermore, the bacterium produces polar flagella which are critical for motility. Flagella are involved in the initial states of pulmonary infection and activate Interleukin-8 production by binding to TLR5 on the apical surface of airway epithelial cells (Sadikot et al., 2005).
Secondary, P. aeruginosa encodes a type III secretion system that is a major determinant of virulence and allows the bacterium to inject toxins into the host cell and requires a pilin-mediated bacterial-epithelial contact. P. aeruginosa secretes four known effector proteins via type-III secretion: ExoS, ExoT, ExoU and ExoY (Galle et al., 2012).
In cooperation with the Institute of Pharmacology of the Hannover Medical School we analyse the role of the effector protein ExoY in the pathogenesis of Pseudomonas aeruginosa in airway infections (Fig 1).
Fig. 1. Cytokine expression after airway infection with P. aeruginosa either expressing functional ExoY (red line) or a catalytically inactive ExoY mutant (black line). ExoY-dependent increase was observed locally and systemically in pro-inflammatory mediators.
In contrast to the invasive properties mediated by the type III secretion system, P. aeruginosa also developed a mechanism to coordinate expression of genes important for adaption to the environment which is controlled by quorum sensing systems, a complex regulatory system involving cell-to-cell signalling (Fig. 2). The activation of the quorum-sensing cascade promotes the formation of biofilms which makes conditions more favourable for bacterial persistence and therefore play an important role in the establishment of chronic infections and the protection of the bacteria against antibiotics.
Fig. 2. The quorum sensing network in P. aeruginosa. The two hierarchically arranged las and rhl quorum sensing circuits are subject to modulation by a number of additional regulators, which finetune the quorum sensing response of the organism (activation, inhibition). From: Environmental Microbiology Volume 7, Issue 4, pages 459-471, 28 JAN 2005
Galle M, Carpentier I, Beyaert R.
Structure and function of the Type III secretion system of Pseudomonas aeruginosa.
Curr Protein Pept Sci. 2012;13:831-42.
Juhas M, Eberl L, Tümmler B.
Quorum sensing: the power of cooperation in the world of Pseudomonas.
Environ Microbiol. 2005 Apr;7(4):459-71. Review..
Sadikot RT, Blackwell TS, Christman JW, Prince AS.
Pathogen-host interactions in Pseudomonas aeruginosa pneumonia.
Am J Respir Crit Care Med. 2005 Jun 1;171(11):1209-23.