Evolution of host adaptation in the Salmonella typhoid toxin.
Evolution of host adaptation in the Salmonella typhoid toxin.
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DOI：
10.1038/s41564-017-0033-2
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发表时间：
2017-12
影响因子：
28.3
通讯作者：
Galán JE
中科院分区：
文献类型：
--
作者：
Gao X;Deng L;Stack G;Yu H;Chen X;Naito-Matsui Y;Varki A;Galán JE
The evolution of virulence traits is central for the emergence or re-emergence of microbial pathogens and for their adaptation to a specific host. Typhoid toxin is an essential virulence factor of the human-adapted bacterial pathogen Salmonella Typhi, the cause of typhoid fever in humans. Typhoid toxin has a unique A2B5 architecture with two covalently linked enzymatic “A” subunits, PltA and CdtB, associated to a homopentameric “B” subunit made up of PltB, which has binding specificity for N-acetylneuraminic acid (Neu5Ac) sialoglycans predominantly present in humans. Here we examined the functional and structural relationship between typhoid toxin and ArtAB, an evolutionarily related AB5 toxin encoded by the broad-host Salmonella Typhimurium. We found that ArtA and ArtB, homologs of PltA and PltB, can form a functional complex with the typhoid toxin CdtB subunit after substitution of a single amino acid in ArtA, while ArtB can form a functional complex with wild type PltA and CdtB. We also found that after addition of a single terminal Cys residue, a CdtB homolog from cytolethal distending toxin can form a functional complex with ArtA and ArtB. In line with the broad host specificity of S. Typhimurium, we found that ArtB binds human glycans, terminated in N-acetylneuraminic acid, as well as glycans terminated in N-glycolylneuraminic acid (Neu5Gc), which are expressed in most other mammals. The atomic structure of ArtB bound to its receptor shows the presence of an additional glycan-binding site, which broadens its binding specificity. Despite equivalent toxicity in vitro, we found that the ArtB/PltA/CdtB chimeric toxin exhibits reduced lethality in an animal model, indicating that the host specialization of typhoid toxin has optimized its targeting mechanisms to the human host. This is a remarkable example of toxin evolution to broaden its enzymatic activities and adapt to a specific host.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1107/s0907444910045749
发表时间：
2011-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Winn MD;Ballard CC;Cowtan KD;Dodson EJ;Emsley P;Evans PR;Keegan RM;Krissinel EB;Leslie AG;McCoy A;McNicholas SJ;Murshudov GN;Pannu NS;Potterton EA;Powell HR;Read RJ;Vagin A;Wilson KS
通讯作者：
Wilson KS
影响因子：
6.4
作者：
Desai PT;Porwollik S;Long F;Cheng P;Wollam A;Bhonagiri-Palsikar V;Hallsworth-Pepin K;Clifton SW;Weinstock GM;McClelland M
通讯作者：
McClelland M
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
64.8
作者：
Byres, Emma;Paton, Adrienne W.;Paton, James C.;Lofling, Jonas C.;Smith, David F.;Wilce, Matthew C. J.;Talbot, Ursula M.;Chong, Damien C.;Yu, Hai;Huang, Shengshu;Chen, Xi;Varki, Nissi M.;Varki, Ajit;Rossjohn, Jamie;Beddoe, Travis
通讯作者：
Beddoe, Travis