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3. Synergistic Antimicrobial Effects of Phage vB_AbaSi_W9 and Antibiotics against Acinetobacter baumannii Infection.

Author

Choi, Yoon-Jung, Kim, Shukho, Shin, Minsang, and Kim, Jungmin

Subjects
CARBAPENEM-resistant bacteria, ACINETOBACTER infections, ANTI-infective agents, MEROPENEM, TIGECYCLINE, ACINETOBACTER baumannii
Abstract

Acinetobacter baumannii is a challenging multidrug-resistant pathogen in healthcare. Phage vB_AbaSi_W9 (GenBank: PP146379.1), identified in our previous study, shows lytic activity against 26 (89.66%) of 29 carbapenem-resistant Acinetobacter baumannii (CRAB) strains with various sequence types (STs). It is a promising candidate for CRAB treatment; however, its lytic efficiency is insufficient for complete bacterial lysis. Therefore, this study aimed to investigate the clinical utility of the phage vB_AbaSi_W9 by identifying antimicrobial agents that show synergistic effects when combined with it. The A. baumannii ATCC17978 strain was used as the host for the phage vB_AbaSi_W9. Adsorption and one-step growth assays of the phage vB_AbaSi_W9 were performed at MOIs of 0.001 and 0.01, respectively. Four clinical strains of CRAB belonging to different sequence types, KBN10P04948 (ST191), LIS2013230 (ST208), KBN10P05982 (ST369), and KBN10P05231 (ST451), were used to investigate phage–antibiotic synergy. Five antibiotics were tested at the following concentration: meropenem (0.25–512 µg/mL); colistin, tigecycline, and rifampicin (0.25–256 µg/mL); and ampicillin/sulbactam (0.25/0.125–512/256 µg/mL). The in vitro synergistic effect of the phage and rifampicin was verified through an in vivo mouse infection model. Phage vB_AbaSi_W9 demonstrated 90% adsorption to host cells in 1 min, a 20 min latent period, and a burst size of 114 PFU/cell. Experiments combining phage vB_AbaSi_W9 with antibiotics demonstrated a pronounced synergistic effect against clinical strains when used with tigecycline and rifampicin. In a mouse model infected with CRAB KBN10P04948 (ST191), the group treated with rifampicin (100 μg/mL) and phage vB_AbaSi_W9 (MOI 1) achieved a 100% survival rate—a significant improvement over the phage-only treatment (8.3% survival rate) or antibiotic-only treatment (25% survival rate) groups. The bacteriophage vB_AbaSi_W9 demonstrated excellent synergy against CRAB strains when combined with tigecycline and rifampicin, suggesting potential candidates for phage–antibiotic combination therapy in treating CRAB infections. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Isolation and Characterization of Novel Bacteriophages to Target Carbapenem-Resistant Acinetobacter baumannii.

Author

Choi, Yoon-Jung, Kim, Shukho, Shin, Minsang, and Kim, Jungmin

Subjects
CARBAPENEM-resistant bacteria, WHOLE genome sequencing, BACTERIAL toxins, TREATMENT effectiveness, DRUG resistance in bacteria, ACINETOBACTER baumannii
Abstract

The spread of multidrug-resistant Acinetobacter baumannii in hospitals and nursing homes poses serious healthcare challenges. Therefore, we aimed to isolate and characterize lytic bacteriophages targeting carbapenem-resistant Acinetobacter baumannii (CRAB). Of the 21 isolated A. baumannii phages, 11 exhibited potent lytic activities against clinical isolates of CRAB. Based on host spectrum and RAPD-PCR results, 11 phages were categorized into four groups. Three phages (vB_AbaP_W8, vB_AbaSi_W9, and vB_AbaSt_W16) were further characterized owing to their antibacterial efficacy, morphology, and whole-genome sequence and were found to lyse 37.93%, 89.66%, and 37.93%, respectively, of the 29 tested CRAB isolates. The lytic spectrum of phages varied depending on the multilocus sequence type (MLST) of the CRAB isolates. The three phages contained linear double-stranded DNA genomes, with sizes of 41,326–166,741 bp and GC contents of 34.4–35.6%. Genome-wide phylogenetic analysis and single gene-based tree construction revealed no correlation among the three phages. Moreover, no genes were associated with lysogeny, antibiotic resistance, or bacterial toxins. Therefore, the three novel phages represent potential candidates for phage therapy against CRAB infections. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Complete genome sequence of the multidrug-resistant clinical isolate Acinetobacter baumannii KBN10P05679: Insights into antimicrobial resistance genotype and potential virulence traits

Author

Islam, Md. Maidul, primary, Kim, Jeongah, additional, Kim, Kyeongmin, additional, Kim, Dooyoung, additional, Akter, Samia, additional, Bang, Seunghyeok, additional, Kim, Shukho, additional, Kim, Jungmin, additional, Lee, Je Chul, additional, and Shin, Minsang, additional

Published
2023
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17. Engineering of lysin by fusion of antimicrobial peptide (cecropin A) enhances its antibacterial properties against multidrug-resistant Acinetobacter baumannii

Author

Islam, Md Maidul, primary, Kim, Dooyoung, additional, Kim, Kyeongmin, additional, Park, Su-Jin, additional, Akter, Samia, additional, Kim, Jeongah, additional, Bang, Seunghyeok, additional, Kim, Shukho, additional, Kim, Jungmin, additional, Lee, Je Chul, additional, Hong, Chang-Won, additional, and Shin, Minsang, additional

Published
2022
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20. Complete genome sequence of the multidrug-resistant clinical isolate Acinetobacter baumanniiKBN10P05679: Insights into antimicrobial resistance genotype and potential virulence traits

Author

Islam, Md. Maidul, Kim, Jeongah, Kim, Kyeongmin, Kim, Dooyoung, Akter, Samia, Bang, Seunghyeok, Kim, Shukho, Kim, Jungmin, Lee, Je Chul, and Shin, Minsang

Abstract

•Acinetobacter baumanniiexhibits antimicrobial resistance to several drugs.•KBN10P05679 harbors genes for antibiotic resistance and virulence factors.•KBN10P05679 is resistant to all tested antibiotics except colistin.•KBN10P05679 has higher biofilm-forming ability than standard A. baumanniistrains.•New strategies are needed for effective treatment of A. baumanniiinfections.

Published
2023
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24. Inverse agonist of estrogen-related receptor γ controls Salmonella typhimurium infection by modulating host iron homeostasis

Author

Kim, Don-Kyu, Jeong, Jae-Ho, Lee, Ji-Min, Kim, Kwang Soo, Park, Seung-Hwan, Kim, Yong Deuk, Koh, Minseob, Shin, Minsang, Jung, Yoon Seok, Kim, Hyung-Seok, Lee, Tae-Hoon, Oh, Byung-Chul, Kim, Jae Il, Park, Hwan Tae, Jeong, Won-Il, Lee, Chul-Ho, Park, Seung Bum, Min, Jung-Joon, Jung, Sook-In, Choi, Seok-Yong, Choy, Hyon E., and Choi, Hueng-Sik

Subjects
Salmonella typhimurium -- Physiological aspects -- Genetic aspects -- Research, Estrogen -- Receptors, Homeostasis -- Health aspects -- Physiological aspects -- Genetic aspects -- Research, Immune response -- Physiological aspects -- Genetic aspects -- Research, Biological sciences, Health
Abstract

In response to microbial infection, expression of the defensin-like peptide hepcidin (encoded by Hamp) is induced in hepatocytes to decrease iron release from macrophages (1). To elucidate the mechanism by [...]

Published
2014

30. Outer membrane vesicles produced by Burkholderia cepacia cultured with subinhibitory concentrations of ceftazidime enhance pro-inflammatory responses

Author

Kim, Se Yeon, Kim, Mi Hyun, Son, Joo Hee, Kim, Seung Il, Yun, Sung Ho, Kim, Kyeongmin, Kim, Shukho, Shin, Minsang, and Lee, Je Chul

Subjects
bacteria, respiratory tract diseases
Abstract

Burkholderia cepacia is an opportunistic pathogen that infects patients with debilitating underlying diseases. This study investigated the production of outer membrane vesicles (OMVs) by B. cepacia cultured with sub-minimum inhibitory concentrations (MICs) of antibiotics and examined their pathogenic roles both in vitro and in vivo. B. cepacia ATCC 25416 produced more OMVs under antibiotic stress conditions than controls. OMVs isolated from B. cepacia cultured in Luria-Bertani (LB) broth (OMVs/LB) induced cytotoxicity and the expression of pro-inflammatory cytokine genes in A549 cells in a dose-dependent manner. Host cell cytotoxicity and pro-inflammatory responses were significantly higher in A549 cells treated with B. cepacia OMVs cultured with 1/4 MIC of ceftazidime (OMVs/CAZ) than in the cells treated with OMVs/LB, OMVs cultured with 1/4 MIC of trimethoprim/sulfamethoxazole (OMVs/SXT), or OMVs cultured with 1/4 MIC of meropenem. Intratracheal injection of B. cepacia OMVs also induced histopathology in vivo in mouse lungs. Expressions of IL-1β and TNF-α genes were significantly up-regulatedin the lungs of mice treated with OMVs/CAZ compared to mice administered other OMVs; the expression of the GRO-α gene, however, was significantly up-regulated in OMVs/SXT. In conclusion, OMVs produced by B. cepacia under different antibiotic stress conditions induce different host responses that may contribute to the pathogenesis of B. cepacia.

Published
2020
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31. Characterization Of Chromosome-Mediated Colistin Resistance In Escherichia coli Isolates From Livestock In Korea

Author

Kim,Shukho, Woo,Jung Hwa, Kim,Nayeong, Kim,Mi Hyun, Kim,Se Yeon, Son,Joo Hee, Moon,Dong Chan, Lim,Suk-Kyung, Shin,Minsang, and Lee,Je Chul

Subjects
Infection and Drug Resistance, polycyclic compounds, bacteria, lipids (amino acids, peptides, and proteins), biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses
Abstract

Shukho Kim,1 Jung Hwa Woo,1 Nayeong Kim,1 Mi Hyun Kim,1 Se Yeon Kim,1 Joo Hee Son,1 Dong Chan Moon,2 Suk-Kyung Lim,2 Minsang Shin,1 Je Chul Lee1 1Department of Microbiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Bacterial Disease Division, Animal and Plant Quarantine Agency, Gimcheon-si, Gyeongsangbuk-do, Republic of KoreaCorrespondence: Je Chul LeeDepartment of Microbiology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of KoreaTel +82-53-420-4844Fax +82-53-427-5664Email leejc@knu.ac.krPurpose: Colistin resistance in gram-negative bacteria from humans and livestock has been increasingly reported worldwide. The aim of this study was to investigate the underlying mechanisms of chromosome-mediated colistin resistance in Escherichia coli isolates from livestock in Korea.Materials and methods: Thirty mcr-1-negative isolates were selected from a collection of colistin-resistant E. coli isolates collected from livestock in 2005 and 2015 in Korea. Amino acid alterations in PmrAB, PhoPQ, MgrB, and PmrD were investigated. Colistin-resistant derivatives were produced by serial passage of colistin-susceptible E. coli isolates in colistin-containing media.Results: Thirty colistin-resistant mcr-negative E. coli isolates were classified into 26 sequence types. Twenty-two isolates carried diverse amino acid alterations in PmrB, PhoP, PhoQ, MgrB, and/or PmrD, whereas no mutation in any of these genes was found in the remaining eight isolates. Sixteen out of the 22 isolates shared a total of nine polymorphic positions that were found in colistin-susceptible E. coli strains. Colistin-resistant derivatives from two colistin-susceptible isolates showed the same genetic alterations that were observed in colistin-resistant clinical isolates.Conclusion: Our results suggest that the mechanism underlying chromosome-mediated colistin resistance remain to be discovered in E. coli. Selective pressure of colistin in vitro induced the same genetic mutations associated with colistin resistance in vivo. Efforts to reduce colistin consumption in livestock should be redoubled, to prevent the occurrence of colistin-resistant E. coli strains.Keywords: colistin resistance, two-component system, livestock, genetic mutation, mcr gene

Published
2019

39. Effects of Silibinin Against Prothrombin Kringle-2-Induced Neurotoxicity in the Nigrostriatal Dopaminergic SystemIn Vivo

Author

Leem, Eunju, primary, Oh, Yong-Seok, additional, Shin, Won-Ho, additional, Jin, Byung Kwan, additional, Jeong, Jae Yeong, additional, Shin, Minsang, additional, Kim, Dong Woon, additional, Jang, Jin-Hyeok, additional, Kim, Hyung-Jun, additional, Ha, Chang Man, additional, Jung, Un Ju, additional, Moon, Gyeong Joon, additional, and Kim, Sang Ryong, additional

Published
2019
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42. Histone and TK0471/TrmBL2 form a novel heterogeneous genome architecture in the hyperthermophilic archaeon Thermococcus kodakarensis

Author

Maruyama, Hugo, Shin, Minsang, Oda, Toshiyuki, Matsumi, Rie, Ohniwa, Ryosuke L, Itoh, Takehiko, Shirahige, Katsuhiko, Imanaka, Tadayuki, Atomi, Haruyuki, Yoshimura, Shige H, and Takeyasu, Kunio

Abstract

Being distinct from bacteria and eukaryotes, Archaea constitute a third domain of living things. The DNA replication, transcription, and translation machineries of Archaea are more similar to those of eukaryotes, whereas the genes involved in metabolic processes show more similarity to their bacterial counterparts. We report here that TK0471/TrmB-like 2 (TrmBL2), in addition to histone, is a novel type of abundant chromosomal protein in the model euryarchaeon Thermococcus kodakarensis . The chromosome of T. kodakarensis can be separated into regions enriched either with histone, in which the genetic material takes on a “beads-on-a-string” appearance, or with TK0471/TrmBL2, in which it assumes a thick fibrous structure. TK0471/TrmBL2 binds to both coding and intergenic regions and represses transcription when bound to the promoter region. These results show that the archaeal chromosome is organized into heterogeneous structures and that TK0471/TrmBL2 acts as a general chromosomal protein as well as a global transcriptional repressor.

Published
2011

47. Outer membrane vesicles produced by Burkholderia cepaciacultured with subinhibitory concentrations of ceftazidime enhance pro-inflammatory responses

Author

Kim, Se Yeon, Kim, Mi Hyun, Son, Joo Hee, Kim, Seung Il, Yun, Sung Ho, Kim, Kyeongmin, Kim, Shukho, Shin, Minsang, and Lee, Je Chul

Abstract

ABSTRACTBurkholderia cepaciais an opportunistic pathogen that infects patients with debilitating underlying diseases. This study investigated the production of outer membrane vesicles (OMVs) by B. cepaciacultured with sub-minimum inhibitory concentrations (MICs) of antibiotics and examined their pathogenic roles both in vitroand in vivo. B. cepaciaATCC 25416 produced more OMVs under antibiotic stress conditions than controls. OMVs isolated from B. cepaciacultured in Luria-Bertani (LB) broth (OMVs/LB) induced cytotoxicity and the expression of pro-inflammatory cytokine genes in A549 cells in a dose-dependent manner. Host cell cytotoxicity and pro-inflammatory responses were significantly higher in A549 cells treated with B. cepaciaOMVs cultured with 1/4 MIC of ceftazidime (OMVs/CAZ) than in the cells treated with OMVs/LB, OMVs cultured with 1/4 MIC of trimethoprim/sulfamethoxazole (OMVs/SXT), or OMVs cultured with 1/4 MIC of meropenem. Intratracheal injection of B. cepaciaOMVs also induced histopathology in vivoin mouse lungs. Expressions of IL-1βand TNF-αgenes were significantly up-regulatedin the lungs of mice treated with OMVs/CAZ compared to mice administered other OMVs; the expression of the GRO-αgene, however, was significantly up-regulated in OMVs/SXT. In conclusion, OMVs produced by B. cepaciaunder different antibiotic stress conditions induce different host responses that may contribute to the pathogenesis of B. cepacia.

Published
2020
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