[Topic : The pharmacokinetic parameters of Pyocyanin, a secreted virulence factor]

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Acknowledgement

I would take this opportunity to thank my research supervisor, family and friends for their support and guidance without which this research would not have been possible.

The Pharmacokinetic Parameters Of Pyocyanin, A Secreted Virulence Factor

Outline

Pseudomonas aeruginosa is an opportunistic pathogen responsible for ventilator-acquired pneumonia, acute lower respiratory tract infections in immunocompromised patients and chronic respiratory infections in cystic fibrosis patients. High incidence, infection severity and increasing resistance characterize P. aeruginosa infections, highlighting the need for new therapeutic options. One such option is to target the many pathogenic mechanisms conferred to P. aeruginosa by its large genome encoding many different virulence factors. This article reviews the pathogenic mechanisms and potential therapies targeting these mechanisms in P. aeruginosa respiratory infections. © 2006 Elsevier SAS. All rights reserved.

Aims & Objectives

Pseudomonas aeruginosa is the most common pathogen responsible for both acute respiratory infections in ventilated or immunocompromised patients and chronic respiratory infections in cystic fibrosis patients. P. aeruginosa is also responsible for excessive mortality in VAP. Adding to the problems of high incidence and infection severity, the resistance resistance of P. aeruginosa to conventional antimicrobial treatment has increased over the past decade. These three problems of high incidence, severity and resistance persist even though they are now broadly recognized and various strategies have been proposed addressing them. Therefore, it is crucial that new therapeutic options for P. aeruginosa infections be explored. Such new options may come from specifically targeting the pathogenic mechanisms of P. aeruginosa. Indeed, P. aeruginosa is a remarkable pathogen in that it is endowed with a uniquely large genome containing genes for many different virulence factors and regulatory mechanisms allowing it to adapt to hostile environments.

P. aeruginosa is an opportunistic pathogen that, after being acquired from the environment, colonizes the respiratory epithelium in patients with predisposing conditions such as cystic fibrosis, mechanical ventilation, immunodeficiency or preexisting respiratory disease. Flagella and pili, the motile surface appendages of P. aeruginosa are responsible for bacterial motility and progression towards epithelial contact. These appendages also act as initial tethers in facilitating bacteria to epithelial cell contact by binding to the epithelial surface glycolipid asialo-GM1. Additionally, lipopolysaccharide (LPS) also plays a similar role in bacterial adhesion through asialo- GM1 binding. These appendages then play a major role in the irreversible adhesion to epithelial cells, which is the initial critical step in colonization of the respiratory epithelium. Upon cell contact, the type III secretion system, a major virulence determinant, is activated. The type III secretion system allows P. aeruginosa to inject secreted toxins through a syringe-like apparatus directly into the eukaryotic cytoplasm. Four effector proteins are known: ExoY, ExoS, ExoT, and ExoU and all participate, at varying levels, in the cytotoxicity of P. aeruginosa leading to invasion and dissemination of P. aeruginosa. Other virulence factors secreted via type II secretion system into the extracellular space such as elastase, alkaline phosphatase, exotoxin A, and phospholipase C also participate in invasion by destroying the protective glycocalix of the respiratory epithelium ...