The Cpx envelope stress response of Pseudomonas aeruginosa and its role in antibiotic resistance

Antibiotic resistance has become a major challenge for modern medicine. Massive use of antibiotics in clinical settings and in agriculture has led to the selection of antibiotic resistant bacteria. A continuous decline in available treatment options for bacterial infections makes treatment of infections with resistant strains particularly challenging. The opportunistic pathogen Pseudomonas aeruginosa is one of the top priority organisms for which novel therapeutic strategies, such as evolution-informed treatments, are urgently required. In this thesis, I studied the contribution of the Cpx envelope stress response system of P. aeruginosa to antibiotic resistance. In contrast to other Gram-negative organisms, the Cpx two-component system of P. aeruginosa is still largely uncharacterised.

This thesis investigated the role of the Cpx stress response system in negative cellular hysteresis – a physiological response to antibiotics resulting in increased susceptibility towards other drugs. Further the influence of mutations in the Cpx system on the resistance profile, growth parameters and in vitro biofilm formation was tested. In summary, this thesis provides an overview of the current understanding of the P. aeruginosa Cpx envelope stress response highlighting differences and similarities to other Gram-negative organisms and their potential implications for the success of antibiotic treatment.

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