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  • American Society for Microbiology  (9)
  • 1
    In: Journal of Virology, American Society for Microbiology, Vol. 95, No. 16 ( 2021-07-26)
    Abstract: Multiple host proteins affect the gene expression of Kaposi's sarcoma-associated herpesvirus (KSHV) during latent and lytic replication. High-mobility group box 1 (HMGB1) serves as a highly conserved chromosomal protein inside the cell and a prototypical damage-associated molecular pattern molecule outside the cell. HMGB1 has been shown to play a pathogenic role in viral infectious diseases and to regulate the lytic replication of KSHV. However, its functional effects on the KSHV life cycle in KSHV-infected cells have not been fully elucidated. Here, we explored the role of intracellular and extracellular HMGB1 in KSHV virion production by employing CRISPR/Cas9-mediated HMGB1 knockout in the KSHV-producing iSLK BAC16 cell line. Intracellular HMGB1 formed complexes with various proteins, and the abundance of HMGB1-interacting proteins changed during latent and lytic replication. Moreover, extracellular HMGB1 was found to enhance lytic replication by phosphorylating JNK. Of note, the expression of viral genes was attenuated during lytic replication in HMGB1 knockout iSLK BAC16 cells, with significantly decreased production of infectious virions compared to that of wild-type cells. Collectively, our results demonstrate that HMGB1 is an important cellular cofactor that affects the generation of infectious KSHV progeny during lytic replication. IMPORTANCE The high-mobility group box 1 (HMGB1) protein has many intra- and extracellular biological functions with an intricate role in various diseases. In certain viral infections, HMGB1 affects the viral life cycle and pathogenesis. In this study, we explored the effects of HMGB1 knockout on the production of Kaposi’s sarcoma-associated herpesvirus (KSHV). HMGB1 knockout decreased virion production in KSHV-producing cells by decreasing the expression of viral genes. The processes by which HMGB1 affects KSHV production may occur inside or outside infected cells. For instance, several cellular and viral proteins interacted with intracellular HMGB1 in a nucleosomal complex, whereas extracellular HMGB1 induced JNK phosphorylation, thereby enhancing lytic replication. Our results suggest that both intracellular and extracellular HMGB1 are necessary for efficient KSHV replication. Thus, HMGB1 may represent an effective therapeutic target for the regulation of KSHV production.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 1495529-5
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  • 2
    Online Resource
    Online Resource
    American Society for Microbiology ; 2003
    In:  Antimicrobial Agents and Chemotherapy Vol. 47, No. 12 ( 2003-12), p. 3704-3707
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 47, No. 12 ( 2003-12), p. 3704-3707
    Abstract: The effects of moxifloxacin, a new methoxyfluoroquinolone, on the production of proinflammatory cytokines from human peripheral blood mononuclear cells (PBMCs) were evaluated. Moxifloxacin inhibited the production of tumor necrosis factor alpha (TNF-α) and/or interleukin-6 (IL-6) by PBMCs stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), and heat-killed bacteria in a concentration-dependent manner without cytotoxic effects. The addition of moxifloxacin reduced the population of cells positive for CD-14 and TNF-α and for CD-14 and IL-6 among the LPS- or LTA-stimulated PBMCs. By Western blot analysis, moxifloxacin pretreatment reduced the degradation of IκBα in LPS-stimulated PBMCs. In conclusion, moxifloxacin could interfere with NF-κB activation by inhibiting the degradation of IκBα and reduce the levels of production of proinflammatory cytokines.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2003
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 3
    In: mBio, American Society for Microbiology, Vol. 8, No. 1 ( 2017-03-08)
    Abstract: Severity of H. pylori -associated disease is directly associated with carriage of the CagA toxin. Though the sequences of the CagA protein can differ across strains, previous analyses showed that virtually all H. pylori strains carry one or no copies of cagA . This study showed that H. pylori can carry multiple tandem copies of cagA that can change dynamically. Isolates harboring more cagA copies produced more CagA, thus enhancing toxicity to host cells. Analysis of 314 H. pylori clinical strains isolated from patients in South Korea and the United States showed that 7.5% of clinical strains in the United States carried multiple cagA copies whereas none of the South Korean strains did. This study demonstrated a novel molecular mechanism by which H. pylori dynamically modulates cagA copy number, which affects CagA expression and activity and may impact downstream development of gastric disease.
    Type of Medium: Online Resource
    ISSN: 2161-2129 , 2150-7511
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2017
    detail.hit.zdb_id: 2557172-2
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  • 4
    Online Resource
    Online Resource
    American Society for Microbiology ; 2003
    In:  Antimicrobial Agents and Chemotherapy Vol. 47, No. 3 ( 2003-03), p. 1161-1164
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 47, No. 3 ( 2003-03), p. 1161-1164
    Abstract: Ciprofloxacin (CPFX) and roxithromycin (RXM) induced apoptosis of activated Jurkat T cells in vitro. CPFX showed concentration-dependent acceleration of apoptosis of activated Jurkat T cells by enhancing the expression of FasL and activities of caspase-3 and -8. RXM accelerated cell death, enhanced expression of FasL and caspase-3 but not caspase-8, and did not show the concentration dependency.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2003
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 5
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 47, No. 12 ( 2003-12), p. 3768-3773
    Abstract: We adopted an in vitro infective endocarditis model (IVIEM) to compare the efficacy of vancomycin (VAN), arbekacin (ABK), and gentamicin (GEN) alone or in combination. Using two strains of clinically isolated methicillin-resistant Staphylococcus aureus , one GEN susceptible (GS171) and one GEN resistant (GR153), fibrin clots were prepared and suspended in the IVIEM. Antibiotics were given as boluses every 6 h (q6h), q12h, or q24h or by continuous infusion with VAN, q12h or q24h with ABK, and q8h or q24h with GEN. For combination treatment, VAN q12h plus ABK q24h and VAN q12h plus GEN q24h were given. Fibrin clots were removed from each model at 0, 8, 24, 32, 48, and 72 h, and the bacterial densities were determined. The number of colonies within the fibrin clot was significantly decreased in all study groups compared with control groups ( P 〈 0.001). When VAN and ABK were administered alone, the number of colonies was significantly lower in GS171 than in GR153 by 8 h after administration ( P = 0.02) and was lowest in GS171 when ABK was administered q12h ( P = 0.01). At 72 h, ABK or VAN alone produced equivalent bacterial reductions regardless of dosing frequency and GEN resistance. In GR153, VAN plus ABK showed an additive effect till 24 h, although VAN plus GEN showed indifference. Our data suggest that ABK could be used as an alternative to VAN in GEN-resistant staphylococcal endocarditis. An additive effect was seen when VAN and ABK were used together in GEN-resistant strains until 24 h; however, further studies are warranted for the clinical application of this combination.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2003
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 6
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 59, No. 4 ( 2015-04), p. 1962-1968
    Abstract: Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is increasingly identified as a cause of acute pyelonephritis (APN) among patients without recent health care contact, i.e., community-associated APN. This case-control study compared 75 cases of community-associated ESBL-EC APN (CA-ESBL) to 225 controls of community-associated non-ESBL-EC APN (CA-non-ESBL) to identify the risk factors for ESBL-EC acquisition and investigate the impact of ESBL on the treatment outcomes of community-associated APN (CA-APN) caused by E. coli at a Korean hospital during 2007 to 2013. The baseline characteristics were similar between the cases and controls; the risk factors for ESBL-EC were age ( 〉 55 years), antibiotic use within the previous year, and diabetes with recurrent APN. The severity of illness did not differ between CA-ESBL and CA-non-ESBL (Acute Physiology and Chronic Health Evaluation [APACHE] II scores [mean ± standard deviation] , 7.7 ± 5.9 versus 6.4 ± 5.3; P = 0.071). The proportions of clinical (odds ratio [OR], 1.76; 95% confidence interval [CI] , 0.57 to 5.38; P = 0.323) and microbiological (OR, 1.16; 95% CI, 0.51 to 2.65; P = 0.730) cures were similar, although the CA-ESBL APN patients were less likely to receive appropriate antibiotics within 48 h. A multivariable Cox proportional hazards analysis of the prognostic factors for CA-APN caused by E. coli showed that ESBL production was not a significant factor for clinical (hazard ratio [HR] , 0.39; 95% CI, 0.12 to 1.30; P = 0.126) or microbiological (HR, 0.49; 95% CI, 0.21 to 1.12; P = 0.091) failure. The estimates did not change after incorporating weights calculated using propensity scores for acquiring ESBL-EC. Therefore, ESBL production did not negatively affect treatment outcomes among patients with community-associated E. coli APN.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2015
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 7
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 43, No. 10 ( 2005-10), p. 5003-5008
    Abstract: There are two ways to assess the susceptibility of human cytomegalovirus (HCMV) to ganciclovir (GCV): one is a genotypic test that detects resistance-related mutations and the other is a phenotypic test that actually assesses susceptibility. The advantages of genotyping the UL97 gene are its rapidity and accuracy. However, to detect novel mutations or mutations affecting the UL54 DNA polymerase, a phenotypic test such as the plaque reduction assay (PRA) is also required. To avoid the shortcomings of PRA such as its time-consuming nature and labor-intensiveness, we developed a time-saving fluorescence-activated cell sorting (TS-FACS) technique. We obtained a GCV 50% inhibitory concentration (IC 50 ) from five clinical isolates and an HCMV laboratory strain (AD169) and compared the results with those from the PRA. The laboratory strain and three clinical isolates were sensitive to GCV. Although there was a minor discrepancy in the case of one of the three isolates, the GCV IC 50 values obtained by TS-FACS analysis correlated well with the results of the PRA. The remaining two isolates were resistant to GCV; one was GCV resistant due to the mutation M460V, and the GCV IC 50 results obtained by TS-FACS analysis and by PRA were also comparable. The advantages of TS-FACS analysis are the shorter time required, the possibility of automation, and its comparability to PRA, considered the gold standard. Thus, TS-FACS analysis may be useful as an alternative to PRA in the clinic.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2005
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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  • 8
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 45, No. 12 ( 2007-12), p. 4021-4026
    Abstract: Studies on the molecular epidemiologic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains have demonstrated their genetic and geographical diversity. In addition, it has been reported that there are genetic differences between community-associated (CA) and health care-associated (HA) MRSA strains. Therefore, we investigated the major epidemiologic characteristics of CA MRSA isolates in South Korea and compared them with those of HA MRSA strains. Distributions of staphylococcal chromosome cassette mec (SCC mec ) types and other molecular features, including the Panton-Valentine leukocidin (PVL) gene, were studied in 138 invasive MRSA isolates. Multiplex type IVA SCC mec was identified as the major CA MRSA infection type (53.1%), with a significantly higher prevalence than in HA MRSA ( P 〈 0.001). One major group of type IVA strains carried a larger atypical class B mec element and new subtypes of ccrA2 (96% amino acid homology). The PVL gene was detected in one USA300-like isolate only. Seven major clone types determined by combinational grouping (genetic background SCC mec typing) showed representative patterns of antimicrobial susceptibilities. We concluded that less multi-drug-resistant strains of clone types B-I and D-1 (genetic background, B and D complexes; type IVA SCC mec ) predominate in CA MRSA and that international PVL-positive strains have not spread in South Korea as yet.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2007
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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  • 9
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 57, No. 7 ( 2019-07)
    Abstract: Global data on the epidemiology and susceptibility of Aspergillus are crucial in the management of invasive aspergillosis. Here, we aimed to determine the characteristics of clinical and environmental Aspergillus isolates, focusing mainly on hematologic malignancy patients. We prospectively collected all consecutive cases and clinical isolates of culture-positive proven/probable invasive aspergillosis patients from January 2016 to April 2018 and sampled the air inside and outside the hospital. Cryptic species-level identification of Aspergillus , antifungal susceptibilities, and cyp51 gene sequencing were performed, and clinical data were analyzed. This study was conducted as part of the Ca tholic Hematology Hospital F ungi E pidemiology (CAFÉ) study. A total of 207 proven/probable invasive aspergillosis and 102 clinical and 129 environmental Aspergillus isolates were included in this analysis. The incidence of proven/probable invasive aspergillosis was 1.3 cases/1,000 patient-days during the study period. Cryptic Aspergillus species accounted for 33.8%, with no differences in proportions between the clinical and environmental isolates. Section Nigri presented a high proportion (70.5%) of cryptic species, mainly from A. tubingensis and A. awamori : the former being dominant in environmental samples, and the latter being more common in clinical isolates ( P 〈 0.001). Of 91 A. fumigatus isolates, azole-resistant A. fumigatus was found in 5.3% of all A. fumigatus isolates. Three isolates presented the TR 34 /L98H mutation of the cyp51A gene. Patients with invasive aspergillosis caused by azole-resistant A. fumigatus showed 100% all-cause mortality at 100 days. This study demonstrates the significant portion of cryptic Aspergillus species and clinical implications of azole resistance and underscores the comparison between clinical and environmental isolates.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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