Isolation and Characterization of Novel Phages Targeting Pathogenic Klebsiella pneumoniae

Klebsiella pneumoniae is a dominant cause of community-acquired and nosocomial infections, specifically among immunocompromised individuals. The increasing occurrence of multidrug-resistant (MDR) isolates has significantly impacted the effectiveness of antimicrobial agents. As antibiotic resistance...

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Autores principales: Na Li, Yigang Zeng, Rong Bao, Tongyu Zhu, Demeng Tan, Bijie Hu
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:b0c0e2a0b88f4b01ba132524a15075682021-12-03T04:51:47ZIsolation and Characterization of Novel Phages Targeting Pathogenic Klebsiella pneumoniae2235-298810.3389/fcimb.2021.792305https://doaj.org/article/b0c0e2a0b88f4b01ba132524a15075682021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.792305/fullhttps://doaj.org/toc/2235-2988Klebsiella pneumoniae is a dominant cause of community-acquired and nosocomial infections, specifically among immunocompromised individuals. The increasing occurrence of multidrug-resistant (MDR) isolates has significantly impacted the effectiveness of antimicrobial agents. As antibiotic resistance is becoming increasingly prevalent worldwide, the use of bacteriophages to treat pathogenic bacterial infections has recently gained attention. Elucidating the details of phage-bacteria interactions will provide insights into phage biology and the better development of phage therapy. In this study, a total of 22 K. pneumoniae isolates were assessed for their genetic and phenotypic relatedness by multi-locus sequence typing (MLST), endonuclease S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and in vitro antibiotic susceptibility testing. In addition, the beta-lactamase gene (blaKPC) was characterized to determine the spread and outbreak of K. pneumoniae carbapenemase (KPC)-producing enterobacterial pathogens. Using these ST11 carbapenem-resistant K. pneumoniae isolates, three phages (NL_ZS_1, NL_ZS_2, and NL_ZS_3) from the family of Podoviridae were isolated and characterized to evaluate the application of lytic phages against the MDR K. pneumoniae isolates. In vitro inhibition assays with three phages and K. pneumoniae strain ZS15 demonstrated the strong lytic potential of the phages, however, followed by the rapid growth of phage-resistant and phage-sensitive mutants, suggesting several anti-phage mechanisms had developed in the host populations. Together, this data adds more comprehensive knowledge to known phage biology and further emphasizes their complexity and future challenges to overcome prior to using phages for controlling this important MDR bacterium.Na LiYigang ZengRong BaoTongyu ZhuDemeng TanBijie HuFrontiers Media S.A.articlebacteriophagephage therapyKlebsiella pneumoniaephage-host interactionsmultidrug resistanceMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic bacteriophage
phage therapy
Klebsiella pneumoniae
phage-host interactions
multidrug resistance
Microbiology
QR1-502
spellingShingle bacteriophage
phage therapy
Klebsiella pneumoniae
phage-host interactions
multidrug resistance
Microbiology
QR1-502
Na Li
Yigang Zeng
Rong Bao
Tongyu Zhu
Demeng Tan
Bijie Hu
Isolation and Characterization of Novel Phages Targeting Pathogenic Klebsiella pneumoniae
description Klebsiella pneumoniae is a dominant cause of community-acquired and nosocomial infections, specifically among immunocompromised individuals. The increasing occurrence of multidrug-resistant (MDR) isolates has significantly impacted the effectiveness of antimicrobial agents. As antibiotic resistance is becoming increasingly prevalent worldwide, the use of bacteriophages to treat pathogenic bacterial infections has recently gained attention. Elucidating the details of phage-bacteria interactions will provide insights into phage biology and the better development of phage therapy. In this study, a total of 22 K. pneumoniae isolates were assessed for their genetic and phenotypic relatedness by multi-locus sequence typing (MLST), endonuclease S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and in vitro antibiotic susceptibility testing. In addition, the beta-lactamase gene (blaKPC) was characterized to determine the spread and outbreak of K. pneumoniae carbapenemase (KPC)-producing enterobacterial pathogens. Using these ST11 carbapenem-resistant K. pneumoniae isolates, three phages (NL_ZS_1, NL_ZS_2, and NL_ZS_3) from the family of Podoviridae were isolated and characterized to evaluate the application of lytic phages against the MDR K. pneumoniae isolates. In vitro inhibition assays with three phages and K. pneumoniae strain ZS15 demonstrated the strong lytic potential of the phages, however, followed by the rapid growth of phage-resistant and phage-sensitive mutants, suggesting several anti-phage mechanisms had developed in the host populations. Together, this data adds more comprehensive knowledge to known phage biology and further emphasizes their complexity and future challenges to overcome prior to using phages for controlling this important MDR bacterium.
format article
author Na Li
Yigang Zeng
Rong Bao
Tongyu Zhu
Demeng Tan
Bijie Hu
author_facet Na Li
Yigang Zeng
Rong Bao
Tongyu Zhu
Demeng Tan
Bijie Hu
author_sort Na Li
title Isolation and Characterization of Novel Phages Targeting Pathogenic Klebsiella pneumoniae
title_short Isolation and Characterization of Novel Phages Targeting Pathogenic Klebsiella pneumoniae
title_full Isolation and Characterization of Novel Phages Targeting Pathogenic Klebsiella pneumoniae
title_fullStr Isolation and Characterization of Novel Phages Targeting Pathogenic Klebsiella pneumoniae
title_full_unstemmed Isolation and Characterization of Novel Phages Targeting Pathogenic Klebsiella pneumoniae
title_sort isolation and characterization of novel phages targeting pathogenic klebsiella pneumoniae
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/b0c0e2a0b88f4b01ba132524a1507568
work_keys_str_mv AT nali isolationandcharacterizationofnovelphagestargetingpathogenicklebsiellapneumoniae
AT yigangzeng isolationandcharacterizationofnovelphagestargetingpathogenicklebsiellapneumoniae
AT rongbao isolationandcharacterizationofnovelphagestargetingpathogenicklebsiellapneumoniae
AT tongyuzhu isolationandcharacterizationofnovelphagestargetingpathogenicklebsiellapneumoniae
AT demengtan isolationandcharacterizationofnovelphagestargetingpathogenicklebsiellapneumoniae
AT bijiehu isolationandcharacterizationofnovelphagestargetingpathogenicklebsiellapneumoniae
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