The Role of Pseudomonas aeruginosa DsbA-1 in Bacterial Pathogenesis: Current Research and Future Prospects

Abstract

Disulfide bond isomerase proteins (Dsbs) have been extensively characterized in gram-negative bacteria. Recently research efforts is being placed on their biology in gram-positive species. Modern “omics” technologies, allowed assessment of the contribution of the Dsbs to bacterial pathogenesis. The author cloned and characterized the dsbA 1 protein from Pseudomonas aeruginosa in the late 1990s. The global proteome analysis demonstrated that the dsbA gene is under the direct regulatory control of the extracytoplasmic function (ECF) sigma factor AlgT(U) or sigma-22. This is unique to P. aeruginosa. Disruption of dsbA gene results in pleiotropic phenotype: defect in assembly of cysteine disulfide bond containing proteins-as shown in many others. Recently, omics-based approaches identified expression changes in dsbA gene under different physiological states of bacterial pathogens-primarily in free-living, biofilm state, or under infectious disease conditions. Involvement of dsbA function in biofilm formation was shown using dsbA gene disruption mutants. This chapter documents past and current findings and concludes with future trends in research on Dsbs including peptidomimetics.