Genetic determinants of host tropism in Klebsiella phages

Bacteriophages play key roles in bacterial ecology and evolution and are potential antimicrobials. However, the determinants of phage-host specificity remain elusive. Here, we isolate 46 phages to challenge 138 representative clinical isolates of Klebsiella pneumoniae, a widespread opportunistic pathogen. Spot tests show a narrow host range for most phages, with <2% of 6,319 phage-host combinations tested yielding detectable interactions. Bacterial capsule diversity is the main factor restricting phage host range. Consequently, phage-encoded depolymerases are key determinants of host tropism, and depolymerase sequence types are associated with the ability to infect specific capsular types across phage families. However, all phages with a broader host range found do not encode canonical depolymerases, suggesting alternative modes of entry. These findings expand our knowledge of the complex interactions between bacteria and their viruses and point out the feasibility of predicting the first steps of phage infection using bacterial and phage genome sequences.

List of contents:

1. Tables:
1.1 Depolymerase_DB (used to detect Dpos in phages)
1.2 Klebsiella_phages_review (Phages from the literature with known capsular tropism)
1.3 Phage_killing_curves (raw data of bactericidal assays performed)
1.4. Phage_receptors (list of candidate bacterial receptors)

2. Scripts:
To obtain the True Positive Rate (TPR) of bacterial and phage traits to predict strain spotting and phage capsular tropism, respectively.

3. PDB files of predicted receptor binding proteins (RBPs) of phages

噬菌体在细菌生态学与进化中发挥核心作用，同时亦是极具潜力的抗菌制剂。然而，噬菌体与宿主间特异性相互作用的决定机制仍有待阐明。本研究分离获得46株噬菌体，用于侵染138株代表性临床分离的肺炎克雷伯菌（Klebsiella pneumoniae）——这是一类广泛流行的条件致病菌。点滴试验结果表明，多数噬菌体的宿主范围较为狭窄，在6319组测试的噬菌体-宿主组合中，可检测到相互作用的比例不足2%。细菌荚膜的多样性是限制噬菌体宿主范围的核心因素。据此，噬菌体编码的解聚酶（depolymerase）是决定宿主嗜性的关键因子，且解聚酶的序列类型与跨不同噬菌体科感染特定荚膜型的能力存在关联。然而，所有筛选得到的宿主范围更广的噬菌体均未编码典型解聚酶，这提示存在其他的宿主侵染途径。本研究成果拓展了我们对细菌与其病毒之间复杂相互作用的认知，并证实了利用细菌与噬菌体基因组序列预测噬菌体侵染早期步骤的可行性。

数据集内容清单：
1. 表格：
1.1 解聚酶数据库（Depolymerase_DB，用于检测噬菌体中的Dpos）
1.2 肺炎克雷伯噬菌体综述库（Klebsiella_phages_review，收录文献中具有已知荚膜嗜性的噬菌体）
1.3 噬菌体杀伤曲线（Phage_killing_curves，收录已开展杀菌试验的原始数据）
1.4 噬菌体受体列表（Phage_receptors，候选细菌受体清单）
2. 脚本：
用于分别计算用于预测菌株点滴试验结果的细菌性状、以及预测噬菌体荚膜嗜性的噬菌体性状的真阳性率（True Positive Rate, TPR）。
3. 噬菌体预测受体结合蛋白（Receptor Binding Protein, RBP）的PDB文件