Evidence status of capsule-resolved phage recognition in multidrug-resistant Klebsiella pneumoniae: receptor specificity, depolymerase coverage, and precision phage therapy readiness

Multidrug-resistant Klebsiella pneumoniae has become a major test case for precision antibacterial therapy because its clinical success combines antimicrobial resistance, capsular immune evasion, biofilm formation, and rapid surface-antigen diversification. Bacteriophages and phage-derived proteins offer a mechanistically distinct antibacterial approach, yet K. pneumoniae phage therapy is constrained by receptor specificity. In encapsulated K. pneumoniae , this specificity is strongly shaped by the capsule-recognition interface, where tail fibers, tailspikes, receptor-binding proteins, and capsule depolymerases determine whether a phage or phage-derived enzyme can engage a particular capsule/KL background. This review synthesizes current evidence on capsule-defined host range in K. pneumoniae phages, emphasizing molecular links among capsular polysaccharides, receptor-binding proteins, tailspikes, and depolymerases. We use phage-visible, partially visible, uncertain, and phage-dark candidate as evidence-status labels for capsule-resolved recognition. Phage-visible denotes direct functional support linking a defined K/KL target to capsule-dependent recognition, adsorption, productive lytic infection, validated receptor-binding protein activity, or capsule-directed depolymerase activity. Partially visible denotes capsule-linked host-range or recognition signals with incomplete mechanistic validation; uncertain denotes incomplete or conflicting evidence; phage-dark candidate identifies K/KL backgrounds without direct experimental capsule-recognition evidence among the studies synthesized here. These labels index evidence strength at the capsule-recognition layer, while isolate-level therapeutic susceptibility also depends on alternative surface receptors, post-entry defenses, and lytic performance. The review integrates this graded framework with a capsule-resolved evidence matrix and representative mechanistic cases, and evaluates precision phage therapy readiness through capsule-resolved bacterial panels, curated receptor-binding protein and depolymerase libraries, quantitative host-range assays, defense-system profiling, manufacturing quality, and clinical matching workflows.

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Publication Details

Journal
Bacteriophage
Published
2026-09-28
DOI
https://doi.org/10.1016/j.phage.2026.100014
Primary Topic
Antibiotic Resistance in Bacteria
Type
article
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article

Evidence status of capsule-resolved phage recognition in multidrug-resistant Klebsiella pneumoniae: receptor specificity, depolymerase coverage, and precision phage therapy readiness

Reuben S. Maghembe, Samweli Y. Bahati
Bacteriophage
Antibiotic Resistance in Bacteria
article

Evidence status of capsule-resolved phage recognition in multidrug-resistant Klebsiella pneumoniae: receptor specificity, depolymerase coverage, and precision phage therapy readiness

Reuben S. Maghembe, Samweli Y. Bahati
article en

Abstract

Multidrug-resistant Klebsiella pneumoniae has become a major test case for precision antibacterial therapy because its clinical success combines antimicrobial resistance, capsular immune evasion, biofilm formation, and rapid surface-antigen diversification. Bacteriophages and phage-derived proteins offer a mechanistically distinct antibacterial approach, yet K. pneumoniae phage therapy is constrained by receptor specificity. In encapsulated K. pneumoniae , this specificity is strongly shaped by the capsule-recognition interface, where tail fibers, tailspikes, receptor-binding proteins, and capsule depolymerases determine whether a phage or phage-derived enzyme can engage a particular capsule/KL background. This review synthesizes current evidence on capsule-defined host range in K. pneumoniae phages, emphasizing molecular links among capsular polysaccharides, receptor-binding proteins, tailspikes, and depolymerases. We use phage-visible, partially visible, uncertain, and phage-dark candidate as evidence-status labels for capsule-resolved recognition. Phage-visible denotes direct functional support linking a defined K/KL target to capsule-dependent recognition, adsorption, productive lytic infection, validated receptor-binding protein activity, or capsule-directed depolymerase activity. Partially visible denotes capsule-linked host-range or recognition signals with incomplete mechanistic validation; uncertain denotes incomplete or conflicting evidence; phage-dark candidate identifies K/KL backgrounds without direct experimental capsule-recognition evidence among the studies synthesized here. These labels index evidence strength at the capsule-recognition layer, while isolate-level therapeutic susceptibility also depends on alternative surface receptors, post-entry defenses, and lytic performance. The review integrates this graded framework with a capsule-resolved evidence matrix and representative mechanistic cases, and evaluates precision phage therapy readiness through capsule-resolved bacterial panels, curated receptor-binding protein and depolymerase libraries, quantitative host-range assays, defense-system profiling, manufacturing quality, and clinical matching workflows.

BacteriophageVol. 1
Openalex Percentile: Top 21%
Antibiotic Resistance in Bacteria
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