An extracellular bacterial pathogen modulates host metabolism to regulate its own sensing and proliferation.
An extracellular bacterial pathogen modulates host metabolism to regulate its own sensing and proliferation.
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DOI：
10.1016/j.cell.2013.12.007
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发表时间：
2014-01-16
期刊：
影响因子：
64.5
通讯作者：
Hanski E
中科院分区：
文献类型：
--
作者：
Baruch M;Belotserkovsky I;Hertzog BB;Ravins M;Dov E;McIver KS;Le Breton YS;Zhou Y;Cheng CY;Hanski E
Successful infection depends on the ability of the pathogen to gain nutrients from the host. The extracellular pathogenic bacterium group A Streptococcus (GAS) causes a vast array of human diseases. By using the quorum sensing sil system as a reporter, we found that during adherence to host cells GAS delivers streptolysin toxins creating endoplasmic reticulum stress. This in turn, increases asparagine (ASN) synthetase expression and the production of ASN. The released ASN is sensed by the bacteria altering the expression of ~17% of GAS genes of which about 1/3 are dependent on the two-component system TrxSR. The expression of the streptolysin toxins is strongly upregulated whereas genes linked to proliferation are downregulated in ASN absence. Asparaginase a widely used chemotherapeutic agent, arrests GAS growth in human blood and blocks GAS proliferation in a mouse model of human bacteremia. These results delineate a pathogenic pathway and propose a new therapeutic strategy against GAS infections.
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DOI：
10.1042/bj20081706
发表时间：
2009-02-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Gjymishka A;Su N;Kilberg MS
通讯作者：
Kilberg MS
影响因子：
11.4
作者：
Hidalgo-Grass, Carlos;Mishalian, Inbal;Hanski, Emanuel
通讯作者：
Hanski, Emanuel
影响因子：
3.4
作者：
Bentley, CC;Hakansson, A;Wessels, MR
通讯作者：
Wessels, MR
影响因子：
3.2
作者：
Chaussee, MA;Callegari, EA;Chaussee, MS
通讯作者：
Chaussee, MS
影响因子：
3.1
作者：
Leday, Temekka V.;Gold, Kathryn M.;McIver, Kevin S.
通讯作者：
McIver, Kevin S.