MdsABC-Mediated Pathway for Pathogenicity in Salmonella enterica Serovar Typhimurium.
MdsABC is a Salmonella-specific tripartite efflux pump that has been implicated in the virulence of Salmonella enterica serovar Typhimurium; however, little is known about the virulence factors associated with this pump. We observed MdsABC expression-dependent alterations in the degree of resistance to extracellular oxidative stress and macrophage-mediated killing. Thin-layer chromatography and tandem mass spectrometry analyses revealed that overexpression of MdsABC led to increased secretion of 1-palmitoyl-2-stearoyl-phosphatidylserine (PSPS), affecting the ability of the bacteria to invade and survive in host cells. Overexpression of MdsABC and external addition of PSPS similarly rendered the mdsABC deletion strain resistant to diamide. Diagonal gel analysis showed that PSPS treatment reduced the diamide-mediated formation of disulfide bonds, particularly in the membrane fraction of the bacteria. Salmonella infection of macrophages induced the upregulation of MdsABC expression and led to an increase of intracellular bacterial number and host cell death, similar to the effects of MdsABC overexpression and PSPS pretreatment on the mdsABC deletion strain. Our study shows that MdsABC mediates a previously uncharacterized pathway that involves PSPS as a key factor for the survival and virulence of S. Typhimurium in phagocytic cells.
Department of Life Science, Chung-Ang University, Seoul, Republic of Korea Department of Food and Animal Biotechnology, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
Saemee
http://orcid.org/0000-0003-0021-8862
S
Song
Department of Life Science, Chung-Ang University, Seoul, Republic of Korea.
Boeun
B
Lee
Department of Life Science, Chung-Ang University, Seoul, Republic of Korea.
Ji-Hyun
JH
Yeom
Department of Life Science, Chung-Ang University, Seoul, Republic of Korea.
Soonhye
S
Hwang
Department of Biological Sciences, Inha University, Incheon, Republic of Korea.
Ilnam
I
Kang
Department of Biological Sciences, Inha University, Incheon, Republic of Korea.
Jang-Cheon
JC
Cho
Department of Food and Animal Biotechnology, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
Nam-Chul
NC
Ha
College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
Jeehyeon
J
Bae
Department of Life Science, Chung-Ang University, Seoul, Republic of Korea kangseok@cau.ac.kr ykim@cu.ac.kr.
Kangseok
K
Lee
Department of Microbiology, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea kangseok@cau.ac.kr ykim@cu.ac.kr.
Yong-Hak
YH
Kim
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D012480:Salmonella Infections / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014774:Virulence
D001426:Bacterial Proteins; D026901:Membrane Transport Proteins