Dataset Information

Deciphering Phage-Host Specificity Based on the Association of Phage Depolymerases and Bacterial Surface Glycan with Deep Learning.

ABSTRACT: Phage tailspike proteins are depolymerases that target diverse bacterial surface glycans with high specificity, determining the host-specificity of numerous phages. To address the challenge of identifying tailspike proteins due to their sequence diversity, we developed SpikeHunter, an approach based on the ESM-2 protein language model. Using SpikeHunter, we successfully identified 231,965 tailspike proteins from a dataset comprising 8,434,494 prophages found within 165,365 genomes of five common pathogens. Among these proteins, 143,035 tailspike proteins displayed strong associations with serotypes. Moreover, we observed highly similar tailspike proteins in species that share closely related serotypes. We found extensive domain swapping in all five species, with the C-terminal domain being significantly associated with host serotype highlighting its role in host range determination. Our study presents a comprehensive cross-species analysis of tailspike protein to serotype associations, providing insights applicable to phage therapy and biotechnology.

SUBMITTER: Yang Y

PROVIDER: S-EPMC10370184 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Deciphering Phage-Host Specificity Based on the Association of Phage Depolymerases and Bacterial Surface Glycan with Deep Learning.

Yang Yiyan Y Dufault-Thompson Keith K Yan Wei W Cai Tian T Xie Lei L Jiang Xiaofang X

bioRxiv : the preprint server for biology 20230616

Phage tailspike proteins are depolymerases that target diverse bacterial surface glycans with high specificity, determining the host-specificity of numerous phages. To address the challenge of identifying tailspike proteins due to their sequence diversity, we developed SpikeHunter, an approach based on the ESM-2 protein language model. Using SpikeHunter, we successfully identified 231,965 tailspike proteins from a dataset comprising 8,434,494 prophages found within 165,365 genomes of five common ...[more]

PMID: 37503040

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Project description:The genome of the multihost bacteriophage ΦK64-1, capable of infecting Klebsiella capsular types K1, K11, K21, K25, K30, K35, K64, and K69, as well as new capsular types KN4 and KN5, was analyzed and revealed that 11 genes (S1-1, S1-2, S1-3, S2-1, S2-2, S2-3, S2-4, S2-5, S2-6, S2-7, and S2-8) encode proteins with amino acid sequence similarity to tail fibers/spikes or lyases. S2-5 previously was shown to encode a K64 capsule depolymerase (K64dep). Specific capsule-degrading activities of an additional eight putative capsule depolymerases (S2-4 against K1, S1-1 against K11, S1-3 against K21, S2-2 against K25, S2-6 against K30/K69, S2-3 against K35, S1-2 against KN4, and S2-1 against KN5) was demonstrated by expression and purification of the recombinant proteins. Consistent with the capsular type-specific depolymerization activity of these gene products, phage mutants of S1-2, S2-2, S2-3, or S2-6 lost infectivity for KN4, K25, K35, or K30/K69, respectively, indicating that capsule depolymerase is crucial for infecting specific hosts. In conclusion, we identified nine functional capsule depolymerase-encoding genes in a bacteriophage and correlated activities of the gene products to all ten hosts of this phage, providing an example of type-specific host infection mechanisms in a multihost bacteriophage.IMPORTANCE We currently identified eight novel capsule depolymerases in a multihost Klebsiella bacteriophage and correlated the activities of the gene products to all hosts of this phage, providing an example of carriage of multiple depolymerases in a phage with a wide capsular type host spectrum. Moreover, we also established a recombineering system for modification of Klebsiella bacteriophage genomes and demonstrated the importance of capsule depolymerase for infecting specific hosts. Based on the powerful tool for modification of phage genome, further studies can be conducted to improve the understanding of mechanistic details of Klebsiella phage infection. Furthermore, the newly identified capsule depolymerases will be of great value for applications in capsular typing.

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Dataset Information

Deciphering Phage-Host Specificity Based on the Association of Phage Depolymerases and Bacterial Surface Glycan with Deep Learning.

Publications

Deciphering Phage-Host Specificity Based on the Association of Phage Depolymerases and Bacterial Surface Glycan with Deep Learning.

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