Aspirin versus Cyclooxygenase-2 Inhibitors as Quorum Sensing Inhibitors of Pseudomonas aeruginosa

Abstract

SUMMARY P seudomonas aeruginosa is a gram negative opportunistic bacillus that primarily infects individuals who are immunocompromised or having breaches in normal barriers such as in cases of burns, using indwelling medical devices, or prolonged use of broad-spectrum antibiotics (De Kievit and Iglewski, 2000). Many factors account for pseudomonal strong resistance to antibiotics like the low outer membrane permeability and the presence of several active multidrug efflux pumps, as well as their existence in biofilm. Biofilm is a complex structure firmly attached to biotic & abiotic surfaces consisting of many bacterial microcolonies in an extracellular polymeric substance with channels for free diffusion of nutrients, waste products & autoinducers (Sanchez et al., 2013). Biofilm production has been accused for emergence of Multi drug resistant (MDR) strains by allowing selection for highly resistant strains (Sanchez et al., 2013). MDR pseudomonal strains are responsible for increased morbidity and mortality among hospitalised patients (Aloush et al., 2006). The growing fear of heading to a postantibiotic era permitted thinking of novel strategies to combat infections focusing on chemicals that decrease bacterial virulence such as quorum sensing inhibitors (QSIs), subsequently facilitating clearance of the bacterial load by the host's self (K Bhardwaj et al., 2013). Quorum sensing (QS) systems are intra- and inter-species' signaling systems present in both gram negative & gram positive bacteria (Sturme et al., 2002) that regulate the expression of several genes, many of which code for virulence factors (Li and Tian, 2012). Each bacterial species secretes and has receptors for one or more chemical signal molecule(s); some diffuse freely into & out of the cell and some are partly effluxed by efflux pump; whenever the local concentration reaches a threshold level (which corresponds to a certain bacterial density- quorum), a set of genes inductions and repressions are activated via an activated transcription factor; allowing for community-based decisions among bacteria (De Kievit and Iglewski, 2000). Biofilm community forms the ideal environment for QS since it allows local elevation of signal molecules concentrations (Li and Tian, 2012) and it is also under QS system control (Davies et al., 1998). Quorum- controlled pseudomonal genes include those essential for biofilm formation as well as elastase-enzyme, rhamnolipids, pyocyanin, proteases, and hemolysin production (Ishida et al., 2007). Quorum sensing inhibitors (QSIs) are chemicals that interfere with QS-controlled gene regulation; these include naturally existing molecules & new synthetic homologues, as well as many drugs that were already in clinical use but for completely different purposes (Yang et al., 2009). Acetylsalicylic acid (aspirin) has been widely studied for this purpose and proved to be a potent QSI (Prithiviraj et al., 2005); the mechanism of inhibitio