Staphylococcus pseudintermedius adenosine synthase inhibits the innate immune response and promotes bacterial survival in canine blood

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Mohamed A Abouelkhair, David A Bemis and Stephen A Kania

University of Tennessee, USA
University of Sadat City, Egypt

: J Immunol Tech Infect Dis

Abstract

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Staphylococcus pseudintermedius is an important opportunistic bacterial pathogen that is the most common cause of canine pyoderma. It is frequently associated with urinary tract, wound and surgical site infections and occasionally causes zoonotic infections in human beings. The development of a staphylococcal vaccine is challenging and prior infection with S. pseudintermedius is not associated with protective immunity. Identification of a novel virulence factor inhibiting phagocytosis and evasion of innate immunity could play an important role in the prevention or treatment of S. pseudintermedius infection. Here, through bioinformaticsbased analysis of S. pseudintermedius genome sequences, we identified a putative adenosine synthase gene (SpdsA) encoding a 5′-nucleotidase. S.pseudintermedius SpdsA protein shares approximately 73.46 % similarity with that of Staphylococcus aureus and 46.44% similarity with that of S. suis type2. Like the orthologous protein in S. aureus it catalyzes the dephosphorylation of adenosine mono- and triphosphates and consequently produces the immune signaling molecule adenosine. Attenuation of this enzyme with selected amino acid substations result in diminished hydrolytic activity on adenosine mono-and triphosphates and low adenosine production. Adenosine perturbation enable escape of S. pseudintermedius from phagocytic clearance in dog blood. In contrast, the addition of SpdsA inhibitor or A2A receptor antagonist to phagocytic cells result in diminished ability of S. pseudintermedius to escape from phagocytic killing. Taken together, these results indicate that SpdsA may play an important role in promoting S. pseudintermedius survival and in inhibiting neutrophil activity by adenosine synthesis.

Biography

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Mohamed A Abouelkhair has completed his Master’s degree from University of Sadat City, Egypt. He is an Assistant Lecturer in Bacteriology, Mycology and Immunology department, University of Sadat city, Egypt. Currently, he is a Graduate PhD student in Comparative and Experimental Medicine Graduate program, college of veterinary medicine, University of Tennessee, USA.