Abstract
The bacterial pathogen Klebsiella pneumoniae causes urinary tract infections in immunocompromised patients. Generally, the overuse of antibiotics contributes to the potential development and the spread of antibiotic resistance. In fact, certain strains of K. pneumoniae are becoming increasingly resistant to antibiotics, making infection by these strains more difficult to treat. The use of bacteriophages to control pathogens may offer a non-antibiotic-based approach to treat multidrug-resistant (MDR) infections. However, a detailed understanding of phage–host interactions is crucial in order to explore the potential success of phage-therapy for treatment. In this study, we investigated the molecular epidemiology of nine carbapenemase-producing K. pneumoniae isolates from a local hospital in Shanghai, China. All strain isolates belong to sequence type 11 (ST11) and harbor the blaKPC-2 gene. The S1-PFGE (S1 nuclease pulsed field gel electrophoresis) pattern of the isolates did not show any relationship to the multilocus sequence typing (MLST) profiles. In addition, we characterized phage 117 and phage 31 and assessed the potential application of phage therapy in treating K. pneumoniae infections in vitro. The results of morphological and genomic analyses suggested that both phages are affiliated to the T7 virus genus of the Podoviridae family. We also explored phage–host interactions during growth in both planktonic cells and biofilms. The phages’ heterogeneous lytic capacities against K. pneumoniae strains were demonstrated experimentally. Subsequent culture and urine experiments with phage 117 and host Kp36 initially demonstrated a strong lytic activity of the phages. However, rapid regrowth was observed following the initial lysis which suggests that phage resistant mutants were selected in the host populations. Additionally, a phage cocktail (117 + 31) was prepared and investigated for antimicrobial activity. In Luria Broth (LB) cultures, we observed that the cocktail showed significantly higher antimicrobial activity than phage 117 alone, but this was not observed in urine samples. Together, the results demonstrate the potential therapeutic value of phages in treating K. pneumoniae urinary tract infections.
Highlights
Klebsiella pneumoniae is a non-motile pathogenic Gram-negative bacterium responsible for nosocomial infections in the urinary tract, respiratory tract, and blood of immunocompromised individuals [1]
Our results are in line with previous studies which showed that sequence type 11 (ST11) is the dominant clone of K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae in China, and is closely related to ST258, only with a single-locus variant [14,22,23]
KPC-producing K. pneumoniae was isolated in Korea, indicating ST11 may be another dominant clone of KPC-producing K. pneumoniae [25]
Summary
Klebsiella pneumoniae is a non-motile pathogenic Gram-negative bacterium responsible for nosocomial infections in the urinary tract, respiratory tract, and blood of immunocompromised individuals [1]. Viruses 2019, 11, 1080 resistance in pathogen communities, polymyxin antibiotics, colistin, have been widely used in antimicrobial prophylaxis as well as treatment of infections caused by carbapenem-resistant strains of K. pneumoniae [3]. Over the past few decades, colistin resistance has emerged and become more common, with strains displaying decreased susceptibility to polymyxins [3]. This suggests that a rapid emergence of pan-drug-resistant (PDR) clones is occurring worldwide [4]. There is a great need for the development of alternative approaches to antibiotics for controlling and preventing K. pneumoniae infections
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
