An Mtb-Human Protein-Protein Interaction Map Identifies a Switch between Host Antiviral and Antibacterial Responses.
An Mtb-Human Protein-Protein Interaction Map Identifies a Switch between Host Antiviral and Antibacterial Responses.
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DOI：
10.1016/j.molcel.2018.07.010
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发表时间：
2018-08-16
期刊：
影响因子：
16
通讯作者：
Krogan NJ
中科院分区：
文献类型：
--
作者：
Penn BH;Netter Z;Johnson JR;Von Dollen J;Jang GM;Johnson T;Ohol YM;Maher C;Bell SL;Geiger K;Golovkine G;Du X;Choi A;Parry T;Mohapatra BC;Storck MD;Band H;Chen C;Jäger S;Shales M;Portnoy DA;Hernandez R;Coscoy L;Cox JS;Krogan NJ
虽然巨噬细胞具有强大的抗菌功能，但结核分枝杆菌（Mtb）在这些先天免疫细胞内复制。巨噬细胞内在细菌控制的决定因素，以及克服它们的Mtb策略，知之甚少。为了进一步研究这些过程，我们使用亲和标签纯化质谱（AP-MS）方法来鉴定187个Mtb-人蛋白质-蛋白质相互作用（PPI），涉及34个分泌型Mtb蛋白。该相互作用图谱揭示了参与Mtb发病机制的两个因素-分泌的Mtb蛋白LpqN及其结合伴侣人泛素连接酶CBL。我们发现lpqN Mtb突变体在巨噬细胞中被减弱，但当CBL被去除时生长恢复。相反，Cbl−/−巨噬细胞对病毒感染有抵抗力，表明CBL调节抗菌和抗病毒免疫之间的细胞内在极化。总的来说，这些发现说明了结核分枝杆菌-人类PPI图的实用性，用于更深入地了解结核分枝杆菌与其宿主之间复杂的相互作用。Penn等人使用亲和标签纯化质谱法生成Mtb-人蛋白质-蛋白质相互作用图谱，揭示了Mtb中的毒力因子LpqN与宿主泛素连接酶CBL之间的联系。CBL抑制lpqN减毒并充当宿主抗细菌和抗病毒应答的开关。
Although macrophages are armed with potent antibacterial functions, Mycobacterium tuberculosis (Mtb) replicates inside these innate immune cells. Determinants of macrophage intrinsic bacterial control, and the Mtb strategies to overcome them, are poorly understood. To further study these processes, we used an affinity tag purification mass spectrometry (AP-MS) approach to identify 187 Mtb-human protein-protein interactions (PPIs) involving 34 secreted Mtb proteins. This interaction map revealed two factors involved in Mtb pathogenesis - the secreted Mtb protein, LpqN, and its binding partner, the human ubiquitin ligase CBL. We discovered that an lpqN Mtb mutant is attenuated in macrophages, but growth is restored when CBL is removed. Conversely, Cbl−/− macrophages are resistant to viral infection, indicating that CBL regulates cell-intrinsic polarization between antibacterial and antiviral immunity. Collectively, these findings illustrate the utility of this Mtb-human PPI map for developing a deeper understanding of the intricate interactions between Mtb and its host. Penn et al. used an affinity tag purification mass spectrometry approach to generate an Mtb-human protein-protein interaction map, uncovering a connection between LpqN, a virulence factor in Mtb and CBL, a host ubiquitin ligase. CBL suppresses lpqN attenuation and acts as a switch for host anti-bacterial and anti-viral responses.
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影响因子：
16
作者：
Davis, Zoe H.;Verschueren, Erik;Jang, Gwendolyn M.;Kleffman, Kevin;Johnson, Jeffrey R.;Park, Jimin;Von Dollen, John;Maher, M. Cyrus;Johnson, Tasha;Newton, William;Jaeger, Stefanie;Shales, Michael;Horner, Julie;Hernandez, Ryan D.;Krogan, Nevan J.;Glaunsinger, Britt A.
通讯作者：
Glaunsinger, Britt A.
影响因子：
2.1
作者：
Grundner C;Cox JS;Alber T
通讯作者：
Alber T
影响因子：
3.4
作者：
Malen, Hiwa;Berven, Frode S.;Wiker, Harald G.
通讯作者：
Wiker, Harald G.
影响因子：
56.9
作者：
Darwin, KH;Ehrt, S;Nathan, CF
通讯作者：
Nathan, CF
影响因子：
7.4
作者：
Clauser, KR;Baker, P;Burlingame, AL
通讯作者：
Burlingame, AL