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Journal of Bacteriology, November 2007, p. 8224-8232, Vol. 189, No. 22
0021-9193/07/$08.00+0     doi:10.1128/JB.00898-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Flagella Facilitate Escape of Salmonella from Oncotic Macrophages{triangledown} ,{dagger}

Gen-ichiro Sano,1 Yasunari Takada,1 Shinichi Goto,1 Kenta Maruyama,1 Yutaka Shindo,2 Kotaro Oka,2 Hidenori Matsui,3 and Koichi Matsuo1*

Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo 160-8582, Japan,1 Center for Biosciences and Informatics, School of Fundamental Science and Technology, Keio University, Kanagawa 223-8522, Japan,2 Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, Tokyo 108-8641, Japan3

Received 8 June 2007/ Accepted 31 August 2007

The intracellular parasite Salmonella enterica serovar Typhimurium causes a typhoid-like systemic disease in mice. Whereas the survival of Salmonella in phagocytes is well understood, little has been documented about the exit of intracellular Salmonella from host cells. Here we report that in a population of infected macrophages Salmonella induces "oncosis," an irreversible progression to eukaryotic cell death characterized by swelling of the entire cell body. Oncotic macrophages (OnM{phi}s) are terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling negative and lack actin filaments (F-actin). The plasma membrane of OnM{phi}s filled with bacilli remains impermeable, and intracellular Salmonella bacilli move vigorously using flagella. Eventually, intracellular Salmonella bacilli intermittently exit host cells in a flagellum-dependent manner. These results suggest that induction of macrophage oncosis and intracellular accumulation of flagellated bacilli constitute a strategy whereby Salmonella escapes from host macrophages.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Phone: (81) 3 3353 1211. Fax: (81) 3 5360 1508. E-mail: matsuo{at}sc.itc.keio.ac.jp

{triangledown} Published ahead of print on 14 September 2007.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

Journal of Bacteriology, November 2007, p. 8224-8232, Vol. 189, No. 22
0021-9193/07/$08.00+0     doi:10.1128/JB.00898-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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