Role of SurA, BamB, BamC and HlpA for shaping the outer membrane protein composition of Pseudomonas aeruginosa

Pseudomonas aeruginosa (Pa) is one of the main causative agents of nosocomial infections and the spread of multidrug-resistant strains is rising. The outer membrane composition of Pa restricts antibiotic entry and determines virulence. For efficient outer membrane protein biogenesis, the BAM complex and chaperones like Skp and SurA are crucial. Deletion mutants of bamB, bamC and the skp homolog hlpA as well as a conditional mutant of surA were investigated. The most profound effects were associated with a lack of SurA, characterized by increased membrane permeability, enhanced sensitivity to antibiotic treatment and attenuation of virulence in a Galleria mellonella infection model. Strikingly, the conditional deletion of surA in a multidrug-resistant bloodstream isolate re-sensitized the strain to antibiotic treatment. Mass spectrometry revealed striking alterations in the outer membrane composition. Thus, SurA of Pa is important for the insertion of many porins, type V secretion systems, TonB-dependent receptors, proteins involved in LPS transport and BAM complex components. Therefore, SurA of Pa serves as a promising target for developing a drug that shows antiinfective activity and sensitizes multidrug-resistant strains to antibiotics.