Gert van der Hoek
In Memoriam - Editor, Senior Moderator
Isolation of a bacteriophage and its depolymerase specific for K1 capsule of Klebsiella pneumoniae: implication in typing and treatment
Tzu-Lung Lin1, Pei-Fang Hsieh1, Yu-Tsung Huang2, Wei-Ching Lee1, Yi-Ting Tsai1, Po-An Su1, Yi-Jiun Pan1, Chun-Ru Hsu1, Meng-Chuan Wu1 and Jin-Town Wang1,3
Abstract
Background. Klebsiella pneumoniae causing community-acquired pyogenic liver abscess (PLA) complicated with metastatic meningitis and endophthalmitis was emerged recently and most frequently associated with the K1 capsular type.
Methods. A bacteriophage (NTUH-K2044-K1-1) that infects K. pneumoniae NTUH-K2044 (capsular type K1) was isolated and characterized
Results. The phage infected all K1 strains, and none of the strains with other capsular types. Capsule deletion mutants were not lysed by this phage, suggesting that the capsule was essential for phage infection. Complete genome sequencing revealed the phage was a novel phiKMV-like virus. The gene encoding capsule depolymerase was identified. The recombinant enzyme demonstrated specific lysis of the K1 capsule. Treatment with the phage or the recombinant enzyme provided significantly increased survival in mice infected with NTUH-K2044 strain, including one treated after the detection of a neck abscess by imaging. No obvious pathology was observed after administration of this phage in mice. Phage was retained at detectable levels in liver, spleen, brain and blood at 24 hours after administration in mice.
Conclusion. These results demonstrate this phage and its capsule depolymerase exhibit specificity for capsular type K1 and can be used for the diagnosis and treatment of K1 K. pneumoniae infections.
JID
thanks to Dave Roberts
Tzu-Lung Lin1, Pei-Fang Hsieh1, Yu-Tsung Huang2, Wei-Ching Lee1, Yi-Ting Tsai1, Po-An Su1, Yi-Jiun Pan1, Chun-Ru Hsu1, Meng-Chuan Wu1 and Jin-Town Wang1,3
Abstract
Background. Klebsiella pneumoniae causing community-acquired pyogenic liver abscess (PLA) complicated with metastatic meningitis and endophthalmitis was emerged recently and most frequently associated with the K1 capsular type.
Methods. A bacteriophage (NTUH-K2044-K1-1) that infects K. pneumoniae NTUH-K2044 (capsular type K1) was isolated and characterized
Results. The phage infected all K1 strains, and none of the strains with other capsular types. Capsule deletion mutants were not lysed by this phage, suggesting that the capsule was essential for phage infection. Complete genome sequencing revealed the phage was a novel phiKMV-like virus. The gene encoding capsule depolymerase was identified. The recombinant enzyme demonstrated specific lysis of the K1 capsule. Treatment with the phage or the recombinant enzyme provided significantly increased survival in mice infected with NTUH-K2044 strain, including one treated after the detection of a neck abscess by imaging. No obvious pathology was observed after administration of this phage in mice. Phage was retained at detectable levels in liver, spleen, brain and blood at 24 hours after administration in mice.
Conclusion. These results demonstrate this phage and its capsule depolymerase exhibit specificity for capsular type K1 and can be used for the diagnosis and treatment of K1 K. pneumoniae infections.
JID
thanks to Dave Roberts