Isolation and characterization of lytic phage TUN1 specific for Klebsiella pneumoniae K64 clinical isolates from Tunisia

BMC Microbiology

Susann Handrick¹  Jana Stender¹  Christina Bugert¹  Joachim J. Bugert¹  Roman Wölfel¹  Simone Eckstein¹  Jana Kühn¹  Daniela Friese¹  Mustapha Ferjani²  Andrew Millard³  Kilian Vogele⁴  Mohamed Ben Moussa⁵  Sonia Mzoughi⁶ 

[1] Bundeswehr Institute of Microbiology, Munich, Germany;Department of Anesthesiology and Reanimation, Military Hospital of Instruction of Tunis, Tunis, Tunisia;Department of Genetics and Genome Biology, University of Leicester, Leicester, UK;Department of Physics, Technical University of Munich, Garching, Germany;Department of Virology, Military Hospital of Instruction of Tunis, Tunis, Tunisia;Department of Virology, Military Hospital of Instruction of Tunis, Tunis, Tunisia;Faculty of Pharmacy, Monastir, Tunisia;

关键词: Multidrug-resistant bacteria;    Klebsiella pneumoniae;    Bacteriophage, phage therapy;   

DOI  :  10.1186/s12866-021-02251-w

来源: Springer

【 摘 要 】

BackgroundMultidrug-resistant Klebsiella pneumoniae spp. (kp) are emerging agents of severe infections of the respiratory, urinary tract and wounds that can progress to fatal septicemia. The use of bacteriophages is currently being considered as an effective alternative or adjuvant to antibiotic therapy.ResultsIn this study, we report capsule (K)-typing of 163 carbapenem-resistant Kp (CRKP) isolated 2014–2018 at the Military Hospital of Instruction of Tunis (MHT), Tunisia, by partial amplification and sequencing of the Kp wzi gene. The most prevalent K-type overall was K64 with 50.3% followed by K17 and K27 (22.7 and 11.0%, respectively). K64 Kp strains were most common and associated with increased case/fatality rates, especially at the intensive care unit (ICU). Using a K64 Kp strain we isolated and characterized a lytic Kp phage, vB_KpP_TUN1 (phage TUN1), from wastewater samples of the ICU at the MHT. TUN1 belongs to the Autographiviridae family and specifically digests K64 Kp capsules most probably via a depolymerase encoded by gp47. Furthermore, we successfully assembled phage TUN1 in a non-replicative host (E. coli) raising the possibility of in vitro assembly in the absence of live bacterial hosts. We propose that phage TUN1 is a promising candidate to be used as an adjuvant or an alternative to antibiotic therapy in CRKP infections, facilitating regulatory approval of phage therapy.ConclusionsK64, K17 and K27 are the most common wzi capsule types in this geographical location in Northern Africa. The lytic phage TUN1 efficiently lyses K64 Kp strains associated with increased case/fatality rates at body temperature. Together with its ability to be rescued in a non-replicative host these features enhance the utility of this phage as an antibacterial agent.

【 授权许可】

CC BY