SurA is required for outer membrane biogenesis and can be used as a new molecular target for plague therapy

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Abstract
Goal. Determination of the role of periplasmic chaperone SurA in the pathogenesis of bubonic and pneumonic plague. MATERIALS AND METHODS Yersinia pestis surA knockout mutants were generated by RedGam mutagenesis with the use of a suicide vector. The generated strains were characterized by their growth rate, sensitivity to antibiotics, bile acid salts and sodium dodecyl sulfate, as well as to the bactericidal action of normal human serum. Intracellular localization of the SurA protein was determined by DSN-PAAG and immunoblot methods. The virulence of the ΔsurA mutant was studied in subcutaneously or intranasally infected mice or rats. RESULTS The SurA-negative Y. pestis strain was characterized by an increase in the permeability of the outer membrane and sensitivity to antibiotics, as well as a decrease in virulence in a model of bubonic and pneumonic plague in two laboratory animal species. CONCLUSION The SurA protein can be considered as a molecular target for plague therapy. Reducing the virulence of a strain and its resistance to antibiotics by disrupting the biogenesis of outer membrane proteins may become a new strategy for solving the problem of combating multidrug resistance, and the widespread distribution of the protein among Gram-negative pathogens makes its use promising for the development of virulence inhibitors with a broad spectrum of action.

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