Background: Presence of capsule enhances the virulence of bacteria that cause pneumonia, meningitis, cystic\nfibrosis, dental caries, periodontitis. Capsule is an important virulence factor for Klebsiella pneumoniae and infections\ndue to this pathogen have been associated with high mortality rates. In the present study, use of an Aeromonas\npunctata derived capsule depolymerase against K. pneumoniae, to reinstate the efficacy of gentamicin during\npneumonia and septicemia was investigated.\nMethods: Depolymerase was administered in mice intraperitoneally (50 ?g) alone as well in combination with\ngentamicin (1.5 mg/kg), 24 h post infection during acute lung infection and 6 h later during septicemia. Bacterial\nload, neutrophil infiltration and cytokine levels were estimated. The immunogenicity of protein was also studied.\nResults: In comparison to groups treated with gentamicin alone, combination treatment with depolymerase and\ngentamicin significantly reduced (P < 0.01) bacterial titer in the lungs, liver, kidney, spleen and blood of\nexperimental animals. Highly significant reduction in neutrophil infiltration and levels of pro-inflammatory and\nanti-inflammatory cytokines was also observed. This indicated an efficient capsule removal by the enzyme, that\nimproved gentamicin efficacy in vivo. Although the enzyme was found to be immunogenic, but no significant\nreduction in treatment efficacy was observed in the preimmunized as well as naÃ?¯ve mice. In addition, as confirmed\nthrough flow cytometry, the hyperimmune sera raised against the enzyme did not neutralize its activity.\nConclusion: The results confirm that administration of enzyme ââ?¬Ë?depolymeraseââ?¬â?¢ along with gentamicin not only\nchecked the virulence of K. pneumoniae in vivo but it also increased its susceptibility to gentamicin at a lower\nconcentration. Such a strategy would help to avoid exposure to higher concentration of gentamicin. Moreover, since\nthis decapsulating protein does not possess a lytic activity therefore there would be no chances of development of\nbacterial resistance against it. Therefore, it should be studied further for its successful inclusion in our prophylactic/\ntherapeutic regimes.
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