Genetic determinants of host tropism in Klebsiella phages

Published: 27 January 2023| Version 2 | DOI: 10.17632/c696dvvynf.2
Beatriz Beamud, Neris García-González, Mar Gómez, Fernando Gonzalez Candelas, Pilar Domingo-Calap, Rafael Sanjuan


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


Steps to reproduce

To calculate the TPR of bacteria: % Rscript calculate_TPR_bacteria_df.r -i Beamud_et_al_Spotting_Matrix_binary_noIHosts_1021.tsv -p TPR_BACT_ALL -m Beamud_et_al_Kpn_collection_metadata_v4_short.csv To calculate the TPR of phages: % Rscript calculate_TPR_phage_df.r -i Beamud_et_al_infection_matrix_CLT_all.tsv -p TPR_PHAGE_ALL -m Beamud_et_al_phage_metadata_rbds_BACKT_final.csv


Universitat de Valencia, Fundacio per al Foment de la Investigacio Sanitaria i Biomedica


Microbiology, Evolutionary Biology, Genomics