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The Klebsiella pneumoniae K64 capsular polysaccharide (K64 CPS) is a complex carbohydrate structure that serves as the outermost layer and primary virulence factor of the bacterium [9, 13]. It plays a fundamental role in pathogenesis by protecting the organism from host immune defenses, specifically by inhibiting phagocytosis by macrophages and neutrophils and preventing the deposition of the complement membrane attack complex [13, 16, 17]. The K64 serotype is particularly notable for its association with hypervirulent and carbapenem-resistant Klebsiella pneumoniae (CRKP) strains, such as the globally spreading ST147 lineage, which are often resistant to nearly all available antibiotics [1, 10]. As a therapeutic target, the K64 capsule is being explored through several innovative strategies. Phage-derived depolymerases, such as K64-ORF41, enzymatically degrade the polysaccharide to strip the bacteria of its protective coating, rendering it vulnerable to the host's innate immune system [2, 4, 7]. Additionally, K64 CPS is a primary target for the development of monoclonal antibodies and bioconjugate vaccines, which aim to promote opsonophagocytic killing and provide targeted antimicrobial action without disrupting the host microbiome [10, 12, 15]. These approaches represent a promising alternative to traditional antibiotics for treating multi-drug resistant Klebsiella infections [5, 8].
Enzymatic degradation of the polysaccharide capsule by phage-derived depolymerases to expose the bacteria to host immune defenses [2, 4]; opsonization and enhancement of phagocytosis by monoclonal antibodies [1, 10]; and induction of protective, serotype-specific immunity via conjugate vaccination [15, 19].
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