Abstract
Carbapenem-resistant Klebsiella pneumoniae (CRKP), one of the major nosocomial pathogens, is increasingly becoming a serious threat to global public health. There is an urgent need to develop effective therapeutic and preventive approaches to combat the pathogen. Here, we identified and characterized a novel capsule depolymerase (K64-ORF41) derived from Klebsiella phage SH-KP152410, which showed specific activities for K. pneumoniae K64-serotype. We showed that this depolymerase could be used in the identification of K64 serotypes based on the capsular typing, and the results agreed well with those from the conventional serotyping method using antisera. From this study, we also identified K64 mutant strains, which showed typing discrepancy between wzi-sequencing based genotyping and depolymerase-based or antiserum-based typing methods. Further investigation indicated that the mutant strain has an insertion sequence (IS) in wcaJ, which led to the alteration of the capsular serotype structure. We further demonstrated that K64-ORF41 depolymerase could sensitize the bacteria to serum or neutrophil killing by degrading the capsular polysaccharide. In summary, the identified K64 depolymerase proves to be an accurate and reliable tool for capsular typing, which will facilitate the preventive intervention such as vaccine development. In addition, the polymerase may represent a potential and promising therapeutic biologics against CRKP-K64 infections.
Highlights
Klebsiella pneumoniae, a Gram-negative, rod-shaped, and encapsulated opportunistic pathogen, causes a wide range of nosocomial infections, including septicemia, pneumonia, urinary tract infections (UTI) and liver abscesses [1]
We identified a phage-derived depolymerase (K64-ORF41), which can degrade the bacterial capsule of K64 serotype K. pneumoniae
K. pneumoniae strain 2410 is a Carbapenem-resistant K. pneumoniae (CRKP) strain, which is resistant to multiple antibiotics, including cefotaxime (CTX), meropenem (MEM), imipenem (IPM), amikacin (AMK), cefuroxime (CXM), gentamicin (GEN), cefazolin (CZO), and piperacillin (PIP)
Summary
Klebsiella pneumoniae, a Gram-negative, rod-shaped, and encapsulated opportunistic pathogen, causes a wide range of nosocomial infections, including septicemia, pneumonia, urinary tract infections (UTI) and liver abscesses [1]. Various antimicrobials have been used to treat K. pneumoniae infections, which has led to a significant rise of antibiotic resistant strains. Among the MDR strains, Carbapenem-resistant K. pneumoniae (CRKP) has posed a significant challenge to the global public health due to lack of the available antibiotics [4]. K. pneumoniae is classified into at least 78 capsular serotypes based on the serological reaction of CPS with specific antisera [7,8]. It is important to determine capsular types of clinical isolates prior to application of any specific medical treatment or future development of CPS-based vaccines [9]. The capsular types of Klebsiella can be identified by a variety of methods. The traditional serological method in determining capsular types was established in 1926 [10]
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