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Inhibition of Autolysis by Lipase LipA in Streptococcus pneumoniae Sepsis

  • Kim, Gyu-Lee (School of Pharmacy, Sungkyunkwan University) ;
  • Luong, Truc Thanh (School of Pharmacy, Sungkyunkwan University) ;
  • Park, Sang-Sang (Department of Microbiology, University of Alabama at Birmingham) ;
  • Lee, Seungyeop (School of Pharmacy, Sungkyunkwan University) ;
  • Ha, Jung Ah (School of Pharmacy, Sungkyunkwan University) ;
  • Nguyen, Cuong Thach (School of Pharmacy, Sungkyunkwan University) ;
  • Ahn, Ji Hye (School of Pharmacy, Sungkyunkwan University) ;
  • Park, Ki-Tae (School of Pharmacy, Sungkyunkwan University) ;
  • Paik, Man-Jeong (College of Pharmacy, Sunchon National University) ;
  • Pyo, Suhkneung (School of Pharmacy, Sungkyunkwan University) ;
  • Briles, David E. (Department of Microbiology, University of Alabama at Birmingham) ;
  • Rhee, Dong-Kwon (School of Pharmacy, Sungkyunkwan University)
  • Received : 2017.09.09
  • Accepted : 2017.11.21
  • Published : 2017.12.31

Abstract

More than 50% of sepsis cases are associated with pneumonia. Sepsis is caused by infiltration of bacteria into the blood via inflammation, which is triggered by the release of cell wall components following lysis. However, the regulatory mechanism of lysis during infection is not well defined. Mice were infected with Streptococcus pneumoniae D39 wild-type (WT) and lipase mutant (${\Delta}lipA$) intranasally (pneumonia model) or intraperitoneally (sepsis model), and survival rate and pneumococcal colonization were determined. LipA and autolysin (LytA) levels were determined by qPCR and western blotting. S. pneumoniae Spd_1447 in the D39 (type 2) strain was identified as a lipase (LipA). In the sepsis model, but not in the pneumonia model, mice infected with the ${\Delta}lipA$ displayed higher mortality rates than did the D39 WT-infected mice. Treatment of pneumococci with serum induced LipA expression at both the mRNA and protein levels. In the presence of serum, the ${\Delta}lipA$ displayed faster lysis rates and higher LytA expression than the WT, both in vitro and in vivo. These results indicate that a pneumococcal lipase (LipA) represses autolysis via inhibition of LytA in a sepsis model.

Acknowledgement

Supported by : National Research Foundation

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