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- Characterization of Newly Isolated Bacteriophages Targeting Carbapenem-Resistant Klebsiella pneumoniae
- Bokyung Kim, Shukho Kim, Yoon-Jung Choi, Minsang Shin, Jungmin Kim
- J. Microbiol. 2024;62(12):1133-1153. Published online December 10, 2024
- DOI: https://doi.org/10.1007/s12275-024-00180-7
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Abstract
- Klebsiella pneumoniae, a Gram-negative opportunistic pathogen, is increasingly resistant to carbapenems in clinical settings. This growing problem necessitates the development of alternative antibiotics, with phage therapy being one promising option. In this study, we investigated novel phages targeting carbapenem-resistant Klebsiella pneumoniae (CRKP) and evaluated their lytic capacity against clinical isolates of CRKP. First, 23 CRKP clinical isolates were characterized using Multi-Locus Sequence Typing (MLST), carbapenemase test, string test, and capsule typing. MLST classified the 23 K. pneumoniae isolates into 10 sequence types (STs), with the capsule types divided into nine known and one unknown type. From sewage samples collected from a tertiary hospital, 38 phages were isolated. Phenotypic and genotypic characterization of these phages was performed using Random Amplification of Polymorphic DNA-PCR (RAPD-PCR), transmission electron microscopy (TEM), and whole genome sequencing (WGS) analysis. Host spectrum analysis revealed that each phage selectively lysed strains sharing the same STs as their hosts, indicating ST-specific activity. These phages were subtyped based on their host spectrum and RAPD-PCR, identifying nine and five groups, respectively. Fourteen phages were selected for further analysis using TEM and WGS, revealing 13 Myoviruses and one Podovirus. Genomic analysis grouped the phages into three clusters: one closely related to Alcyoneusvirus, one to Autographiviridae, and others to Straboviridae. Our results showed that the host spectrum of K. pneumoniae-specific phages corresponds to the STs of the host strain. These 14 novel phages also hold promise as valuable resources for phage therapy against CRKP.
- Varicella‑Zoster Virus ORF39 Transmembrane Protein Suppresses Interferon‑Beta Promoter Activation by Interacting with STING
- Gwang Myeong Lee , Shuang Gong , Seong&# , Hyemin Ko , Woo&# , Jihyun Lee , Ok Sarah Shin , Jin&#
- J. Microbiol. 2023;61(2):259-270. Published online February 20, 2023
- DOI: https://doi.org/10.1007/s12275-023-00019-7
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Abstract
- Varicella-Zoster virus (VZV) causes varicella in primary infection of children and zoster during reactivation in adults. Type I interferon (IFN) signaling suppresses VZV growth, and stimulator of interferon genes (STING) plays an important role in anti-VZV responses by regulating type I IFN signaling. VZV-encoded proteins are shown to inhibit STING-mediated activation of the IFN-β promoter. However, the mechanisms by which VZV regulates STING-mediated signaling pathways are largely unknown. In this study, we demonstrate that the transmembrane protein encoded by VZV open reading frame (ORF) 39 suppresses STING-mediated IFN-β production by interacting with STING. In IFN-β promoter reporter assays, ORF39 protein (ORF39p) inhibited STING-mediated activation of the IFN-β promoter. ORF39p interacted with STING in co-transfection assays, and this interaction was comparable to that of STING dimerization. The cytoplasmic N-terminal 73 amino acids region of ORF39P was not necessary for ORF39 binding and suppression of STING-mediated IFN-β activation. ORF39p also formed a complex containing both STING and TBK1. A recombinant VZV expressing HA-tagged ORF39 was produced using bacmid mutagenesis and showed similar growth to its parent virus. During HA-ORF39 virus infection, the expression level of STING was markedly reduced, and HA-ORF39 interacted with STING. Moreover, HA-ORF39 also colocalized with glycoprotein K (encoded by ORF5) and STING at the Golgi during virus infection. Our results demonstrate that the transmembrane protein ORF39p of VZV plays a role in evading the type I IFN responses by suppressing STINGmediated activation of the IFN-β promoter.
Review
- REVIEW] Antibiotic-resistant clones in Gram-negative pathogens: presence of global clones in Korea
- Kwan Soo Ko
- J. Microbiol. 2019;57(3):195-202. Published online October 2, 2018
- DOI: https://doi.org/10.1007/s12275-019-8491-2
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- 7 Web of Science
- 9 Crossref
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Abstract
- Antibiotic resistance is a global concern in public health. Antibiotic-resistant clones can spread nationally, internationally, and globally. This review considers representative antibiotic-resistant Gram-negative bacterial clones–CTX-M- 15-producing ST131 in Escherichia coli, extended-spectrum β-lactamase-producing ST11 and KPC-producing ST258 in Klebsiella pneumoniae, IMP-6-producing, carbapenem-resistant ST235 in Pseudomonas aeruginosa, and OXA-23- producing global clone 2 in Acinetobacter baumannii–that have disseminated worldwide, including in Korea. The findings highlight the urgency for systematic monitoring and international cooperation to suppress the emergence and propagation of antibiotic resistance.
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Citations
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- Molecular epidemiology of carbapenem-resistant gram-negative bacilli in Ecuador
Claudia Soria-Segarra, Carmen Soria-Segarra, Marcos Molina-Matute, Ivanna Agreda-Orellana, Tamara Núñez-Quezada, Kerly Cevallos-Apolo, Marcela Miranda-Ayala, Grace Salazar-Tamayo, Margarita Galarza-Herrera, Victor Vega-Hall, José E. Villacis, José Gutiérr
BMC Infectious Diseases.2024;[Epub] CrossRef - Epidemiological and Molecular Characteristics of blaNDM-1 and blaKPC-2 Co-Occurrence Carbapenem-Resistant Klebsiella pneumoniae
Fang Rong, Ziyi Liu, Pengbin Yang, Feng Wu, Yu Sun, Xuewei Sun, Jun Zhou
Infection and Drug Resistance.2023; Volume 16: 2247. CrossRef - Gold nanoparticle-DNA aptamer-assisted delivery of antimicrobial peptide effectively inhibits Acinetobacter baumannii infection in mice
Jaeyeong Park, Eunkyoung Shin, Ji-Hyun Yeom, Younkyung Choi, Minju Joo, Minho Lee, Je Hyeong Kim, Jeehyeon Bae, Kangseok Lee
Journal of Microbiology.2022; 60(1): 128. CrossRef -
Molecular Characterization of Carbapenem-resistant, Colistin-resistant Klebsiella pneumoniae Isolates from a Tertiary Hospital in Jeonbuk, Korea
Tae Hee Lee, Minhyeon Cho, Jaehyeon Lee, Joo-Hee Hwang, Chang-Seop Lee, Kyung Min Chung
Journal of Bacteriology and Virology.2021; 51(3): 120. CrossRef - Transmission Dynamics of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 Strains Carrying Capsular Loci KL64 and rmpA/rmpA2 Genes
Yingying Kong, Qingyang Sun, Hangfei Chen, Mohamed S. Draz, Xinyou Xie, Jun Zhang, Zhi Ruan
Frontiers in Microbiology.2021;[Epub] CrossRef - Microbiota of the lower respiratory tract in community-acquired pneumonia, including cases associated with SARS-CoV-2
L. V. Kataeva, A. A. Vakarina, T. F. Stepanova, K. B. Stepanova
Journal of microbiology, epidemiology and immunobiology.2021; 98(5): 528. CrossRef - Global Evolution of Pathogenic Bacteria With Extensive Use of Fluoroquinolone Agents
Miklos Fuzi, Jesus Rodriguez Baño, Akos Toth
Frontiers in Microbiology.2020;[Epub] CrossRef - Emergence, molecular mechanisms and global spread of carbapenem-resistant Acinetobacter baumannii
Mohammad Hamidian, Steven J. Nigro
Microbial Genomics .2019;[Epub] CrossRef - Perspectives towards antibiotic resistance: from molecules to population
Joon-Hee Lee
Journal of Microbiology.2019; 57(3): 181. CrossRef
- Molecular epidemiology of carbapenem-resistant gram-negative bacilli in Ecuador
Research Support, Non-U.S. Gov't
- Molecular Analysis of a Prolonged Spread of Klebsiella pneumoniae Co-producing DHA-1 and SHV-12 β-Lactamases
- Young Kyung Yoon , Hye Won Cheong , Hyunjoo Pai , Kyoung Ho Roh , Jeong Yeon Kim , Dae Won Park , Jang Wook Sohn , Seung Eun Lee , Byung Chul Chun , Hee Sun Sim , Min Ja Kim
- J. Microbiol. 2011;49(3):363-368. Published online June 30, 2011
- DOI: https://doi.org/10.1007/s12275-011-0491-9
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- 4 Scopus
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Abstract
- The study investigated molecular mechanisms for prolonged nosocomial spread of multidrug-resistant Klebsiella pneumoniae co-producing plasmid-mediated AmpC β-lactamase DHA-1 and extended-spectrum β-lactamase SHV-12. Forty-eight clinical isolates of K. pneumonia, resistant to the extended-spectrum cephalosporins, were collected in a 750-bed university hospital over a year. The isolates were characterized for PCR-based β-lactamase genotypes, isoelectric focusing and pulsed-field gel electrophoresis (PFGE) profiles. Resistance transfer was performed by plasmid conjugation and confirmed by a duplex-PCR and Southern hybridization. On β-lactamase typing, the strains producing only the DHA-1 enzyme (n=17) or co-producing DHA-1 and SHV-12 enzymes (n=15) were predominant. Judging from a one year-distribution of PFGE profiles, the co-producer was spread primarily with single clonal expansion of the PFGE-type A with subtypes (n=14), whereas the strains producing only DHA-1 enzyme were spread simultaneously with the PFGE-type A (n=11) and other PFGE types (n=6). Transconjugants of the co-producers were confirmed to harbor either both blaDHA-1 and blaSHV-12 or only the blaDHA-1. In conclusion, this study indicated that the persistent nosocomial spread of multidrug-resistant K. pneumoniae strains was primarily associated with expansion of a clone harboring both the blaDHA-1 and blaSHV-12 or the blaDHA-1 only, and to a lesser extent with the horizontal transfer of the resistant plasmids. Our observations have clinical implication for the control and prevention of nosocomial dissemination of multidrug-resistant K. pneumoniae strains.
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