Many important bacterial pathogens, including the important ESKAPE pathogen Klebsiella pneumoniae, encode and express polysaccharide capsules as their outermost cell structure. These structures are often key virulence factors, aiding in host immune evasion and providing protection from cellular and humoral immune responses. There is growing evidence that removal of these protective capsules, via administration of selective capsule depolymerases, results in rapid elimination of pathogens by the host. Such an approach should be successful against antibiotic-resistant isolates and, therefore, capsule depolymerases represent attractive future therapeutics.
In a recent publication, AROM’s David Negus and collaborators identified, cloned and tested a number of phage-derived capsule depolymerases selective for prevalent K. pneumoniae K-types (capsule types). In the study, over 60 lytic K. pneumoniae phages were isolated and analysis of whole-genome sequence data was used to identify phage-encoded depolymerases. Three of these enzymes were cloned and expressed as recombinant proteins. Using microscopy, the researchers show these depolymerases rapidly remove the capsule from the surface of K. pneumoniae isolates.
These enzymes may provide the basis for a future therapy against antibiotic-resistant K. pneumoniae infections.
Blundell-Hunter G, Enright MC, Negus D, et al. Characterisation of bacteriophage-encoded depolymerases selective for key Klebsiella pneumoniae capsular exopolysaccharides. Front Cell Infect Microbiol. 2021; doi.org/10.3389/fcimb.2021.686090.