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Science 5 November 2004:
Vol. 306. no. 5698, pp. 1037 - 1040
DOI: 10.1126/science.1103966
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Reports

Autophagy Defends Cells Against Invading Group A Streptococcus

Ichiro Nakagawa,1,3* Atsuo Amano,2,4 Noboru Mizushima,3,5 Akitsugu Yamamoto,6 Hitomi Yamaguchi,7 Takahiro Kamimoto,7 Atsuki Nara,6,7 Junko Funao,1 Masanobu Nakata,1 Kayoko Tsuda,7 Shigeyuki Hamada,1 Tamotsu Yoshimori4,7*

We found that the autophagic machinery could effectively eliminate pathogenic group A Streptococcus (GAS) within nonphagocytic cells. After escaping from endosomes into the cytoplasm, GAS became enveloped by autophagosome-like compartments and were killed upon fusion of these compartments with lysosomes. In autophagy-deficient Atg5–/– cells, GAS survived, multiplied, and were released from the cells. Thus, the autophagic machinery can act as an innate defense system against invading pathogens.

1 Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita-Osaka 565-0871, Japan.
2 Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita-Osaka 565-0871, Japan.
3 PRESTO, Japan Science and Technology Agency, Kawaguchi-Saitama 332-0012, Japan.
4 CREST, Japan Science and Technology Agency, Kawaguchi-Saitama 332-0012, Japan.
5 Department of Bioregulation and Metabolism, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
6 Department of Cell Biology, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama-Shiga 526-0829, Japan.
7 Department of Cell Genetics, National Institute of Genetics/SOKENDAI, Yata 1111, Mishima-Shizuoka 411-8540, Japan.

* To whom correspondence should be addressed. E-mail: ichiro{at}dent.osaka-u.ac.jp and tamyoshi{at}lab.nig.ac.jp

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Science. ISSN 0036-8075 (print), 1095-9203 (online)