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Iron and phosphate linked with virulence of bacteria

Pseudomonas aeruginosa (P. aeruginosa) is opportunistic because it attacks patients whose immune systems are compromised. To tackle this often antibiotic resistant bacterium, researchers looked at factors that trigger virulence.
Iron and phosphate linked with virulence of bacteria
Researchers with the EU-funded CSS AND VIRULENCE (Knowing the enemy: unravelling a novel regulatory system involved in bacterial virulence) project have recently discovered a new cell-surface signalling (CSS) regulatory system. In response to a human host signal, P. aeruginosa promptly releases virulence factors that are subsequently activated.

The P. aeruginosa PUMA3 system consists of an extracytoplasmic function (ECF) sigma factor, a sigma factor regulator in the cytoplasmic membrane, and a receptor. The bacterium has no less than 19 ECF sigma factors and these are controlled by anti-sigma factors that bind to the sigma factor to prevent its action.

Two factors that control virulence in the host were investigated by the CSS AND VIRULENCE project – iron and phosphate. Another environmental signal, phosphate starvation, which is also encountered during the infection process, is necessary for expression of the PUMA3 CSS system of P. aeruginosa.

CSS AND VIRULENCE researchers discovered that activation occurs through a complex proteolytic cascade that processes the anti-sigma factor component and liberates the ECF sigma factor. Prior to this research, it was widely held that activation of ECF sigma factors by CSS occurred via conformational changes of the CSS proteins in response to the CSS signal.

The researchers have elucidated the molecular mechanism responsible for transduction of the signal from the bacterial surface to the cytosol via CSS. This has driven refinement of the initial CSS model.

Knowledge of host-pathogen interaction can be exploited for the rational design of molecules targeting crucial pathways. CSS AND VIRULENCE has identified potential targets to inhibit such interactions, and therefore bacterial virulence. The clinical implications are significant as this will determine the way bacterial infections, and Pseudomonas infections in particular, can be treated effectively.

Related information

Keywords

Iron, phosphate, virulence, Pseudomonas aeruginosa, CSS AND VIRULENCE, cell-surface signaling
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