Multidrug Resistance in Pseudomonas Aeruginosa Infections

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The cause of acute, persistent, or relapsing clinical infections is often due to multidrug resistance and/or antibiotic tolerance. Pseudomonas aeruginosa is a widespread, opportunistic, gram-negative, bacterial pathogen that readily develops multidrug resistance and is responsible for causing acute and persistent infections (Starkey et al, 2014). P. aeruginosa thrives in moist environments, primarily as waterborne and soil-borne organisms (Chen, 2015). It is found on medical equipment including catheters, which can cause cross-infections in hospitals and lead to nosocomial infections. If P. aeruginosa is found in the lungs, the urinary tract, or the kidneys, the results can be fatal (Chen, 2015). In addition to causing life-threatening diseases, …show more content…

Quorum sensing is a cell-to-cell density dependent communication system mediated via the production of and regulation by low molecular weight signaling molecules (Starkey et al, 2014). Quorum sensing is crucial for the development of biofilms, which aid in the maintenance and antibiotic tolerance of acute and persistent human infections. P. aeruginosa has three distinct quorum sensing systems mediated by cell-to-cell signals including the las, rhl, and mvfR system (Starkey et al 2014). In this study they targeted the bacterial communication system mvfR, which is essential to the full virulence of P. aeruginosa. MvfR binds to and activates the pqs operon, which encodes for the synthesis of PQS, HHQ and 2-AA. Both PQS and HHQ bind to and activate mvfR, which leads to the production of mvfR virulence factors that promote acute and persistent infections. By identifying quorum sensing inhibitors, they were able to inhibit the mvfR virulence regulon, which disrupted cell-to-cell communication and limited P. aeruginosa infections and lethality in mice. These inhibitors are the first identified compounds that restrict the formation of antibiotic-tolerant persister cells and restrict persistent infections in mice (Starkey et al,

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