Capsule types driving carbapenem-resistant Klebsiella pneumoniae in Pakistan are largely absent from the phage literature

Abstract Phage therapy is increasingly proposed for carbapenem-resistant Klebsiella pneumoniae , but most Klebsiella phages bind a single capsule type, so a phage is useful only where its capsule type circulates. We asked whether published phages cover the capsule types found in Pakistani patients. We typed 254 clinical K. pneumoniae genomes from Pakistan and curated the phage and depolymerase literature into 34 phage–capsule records covering 27 phages and 15 capsule types. Nearly half the cohort was unmatched: 121 of 254 isolates (47.6%), spanning 51 of 66 capsule types, belong to types for which no phage has been described, and 67 of those isolates carry a carbapenemase. Collapsing each BioProject to one isolate per type raises the unmatched fraction to 51.8%. To ask why, we typed 475 genomes sampled on identical criteria from India, Bangladesh and Nepal, China, Europe and the USA. Two capsule types separated sharply. KL81 accounted for 6.3% of South Asian genomes and none of 275 from China, Europe or the USA, and has no published phage; KL107 showed the reverse, 9.8% in those regions and absent from South Asia. Both survived collapsing ( P = 0.0014 and P = 0.0002). Six further differences did not, and are attributable to clonal expansion within single studies. Phages are isolated against locally available hosts, so the capsule types entering the global phage collection track the regions doing the isolating. KL81 is a defined target for phage isolation in South Asia. Impact Statement Phage therapy is one of the few remaining options for carbapenem-resistant Klebsiella pneumoniae , and because most Klebsiella phages recognise a single capsule type, a cocktail only helps where its capsule types circulate. This study shows that almost half of Pakistani clinical isolates belong to capsule types for which no phage has ever been described, and that the gap is not random: the uncovered types are South Asian ones that are rare or absent in the countries where Klebsiella phages are isolated. The global phage collection reflects the capsule distribution of the regions doing the sampling. The practical consequence is that imported cocktails are unlikely to fit South Asian patients, and that KL81 — absent from 275 genomes from China, Europe and the USA, and carbapenemase-positive in every Pakistani isolate examined — is a specific, justified target for local phage isolation. Data Summary All genome data analysed are publicly available assemblies from NCBI. Pakistani cohort: 254 Klebsiella pneumoniae assemblies, accessions listed in Table S1. Comparison cohort: 475 assemblies from India, Bangladesh, Nepal, China, Europe and the USA, accessions listed in Table S2. Source metadata: NCBI Pathogen Detection release PDG000000012.2494, https://www.ncbi.nlm.nih.gov/pathogens/ Curated phage–capsule evidence table (34 records, 27 phages, 15 capsule types) with PMIDs and DOIs: Table S3. Capsule typing performed with Kleborate v3.2.4 and Kaptive v3.2.2, both openly available ( https://github.com/klebgenomics ). Analysis code: https://github.com/wwwtalalahmed98-collab/phagematch-pk , archived at Zenodo, doi:10.5281/zenodo.22025259 (concept DOI, resolving to the most recent version; the version analysed here is v1.0.0, doi:10.5281/zenodo.22025260). No new sequence data were generated by this study.