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JB Accepts, published online ahead of print on 14 September 2007
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J. Bacteriol. doi:10.1128/JB.00898-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Flagella facilitate escape of Salmonella from oncotic macrophages

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

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

* To whom correspondence should be addressed. Email: matsuo{at}sc.itc.keio.ac.jp.


   Abstract

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 induce "oncosis," an irreversible progression to eukaryotic cell death characterized by swelling of the entire cell body. Oncotic macrophages (OnM{Phi}s) are TUNEL-negative and lack actin filaments (F-actin). The plasma membrane of OnM{Phi}s filled with bacilli remains impermeable and intracellular Salmonella move vigorously using flagella. Eventually, intracellular Salmonella intermittently exit host cells in a flagella-dependent manner. These results suggest that induction of macrophage oncosis and intracellular accumulation of flagellated bacilli constitute a strategy whereby Salmonella escape host macrophages.







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