Publications by authors named "Sang-Ho Choi"

398 Publications

Performance of Xpert MTB/RIF for the Diagnosis of Extrapulmonary Tuberculosis.

Clin Lab 2021 Feb;67(2)

Background: Mycobacterial burden is low in extrapulmonary specimens, making diagnosis and treatment difficult. Xpert MTB/RIF is a real-time PCR assay for the detection of Mycobacterium tuberculosis and rifampin resistance. This study evaluated the performance of the Xpert MTB/RIF assay in extrapulmonary specimens.

Methods: Acid-Fast Bacilli (AFB) smear, culture, and Xpert MTB/RIF were performed on extrapulmonary specimens. Mycobacterial culture was performed on BACTEC MGIT liquid for 6 weeks and 2% Ogawa medium for 8 weeks. Overall sensitivity and specificity of Xpert MTB/RIF was estimated using culture as a gold standard. Xpert MTB/RIF sensitivity and cycle-threshold (Ct) values according to AFB smear grade were evaluated. The sensitivity, specificity, and concordance of rifampin resistance compared to the phenotypic drug sensitivity test were evaluated.

Results: A total of 1,289 specimens were included in the study. The overall sensitivity and specificity of the Xpert MTB/RIF assay were 59.4% (41/69, 95% CI 46.9 - 70.9%) and 99.3% (1,212/1,220, 95% CI 98.7 - 99.7), respectively. Positive predictive value of Xpert MTB/RIF was 83.7% (41/49, 95% CI 69.8 - 92.2) and negative predictive value was 97.7% (1,212/1,240, 95% CI 96.7 - 98.5%). Xpert MTB/RIF assay sensitivity significantly increased with increases in AFB smear grade (p < 0.001). AFB smear grades and Xpert MTB/RIF Ct values were negatively correlated. Rifampin resistance results of Xpert MTB/RIF and culture showed a concordance rate of 97.2%.

Conclusions: The Xpert MTB/RIF assay could be used to replace the AFB smear for the diagnosis of extrapulmonary tuberculosis, and has high specificity for the detection of rifampin resistance.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200423DOI Listing
February 2021

Etiology, Characteristics, and Outcomes of Community-Onset Pyomyositis in Korea: A Multicenter Study.

Infect Chemother 2021 Jan 7. Epub 2021 Jan 7.

The Korean Skin and Soft Tissue Study Group, Korea.

Background: Pyomyositis (PM) is a serious soft tissue infection and despite its clinical importance, previous studies have not been able to fully determine the clinical characteristics and microbial epidemiology of PM in Korea, which we therefore aimed to investigate.

Materials And Methods: We retrospectively identified 140 adult patients diagnosed with PM from 13 general hospitals between January 2012 and December 2015. We analyzed the clinical and microbial characteristics of community-onset PM and compared them with community-acquired (CA) and healthcare-associated (HCA) PM.

Results: One hundred eleven organisms were isolated from 96 (68.6%) patients with PM. (38 patients) was the most common pathogen, followed by streptococci (24 patients), and enteric Gram-negative organisms (27 patients). Methicillin-resistant (MRSA) was identified in four (2.9%) patients and in-hospital mortality reached 8.6% (12/140). Enterococci isolates were identified in the HCA PM subgroup only The proportion of MRSA isolates was not comparable between CA and HCA PM subgroups. In the 83 patients with PM infected by monomicrobial pathogens, isolates of Gram-negative organisms were more commonly found in HCA PM subgroup than in CA PM subgroup (47.6% [10/21] of patients with HCA PM 20.7% [12/58] of patients with CA PM; = 0.01).

Conclusion: Gram-positive cocci such as and streptococci were dominant etiologies in community-onset PM, whereas MRSA appears to an uncommon causative organism of PM in Korea. Enteric Gram-negative organisms should also be considered as major etiologies, especially in HCA PM patient population in Korea.
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http://dx.doi.org/10.3947/ic.2020.0102DOI Listing
January 2021

Epidemiology and Clinical Characteristics of Bloodstream Infection in Patients Under Extracorporeal Membranous Oxygenation.

J Intensive Care Med 2020 Dec 30:885066620985538. Epub 2020 Dec 30.

Department of Infectious Diseases, 65526Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: Bloodstream infection (BSI) is an important complication of extracorporeal membranous oxygenation (ECMO) and a major cause of mortality. This study evaluated the epidemiological and clinical characteristics of BSI that occur during ECMO application according to microbial etiology.

Methods: Adult patients who underwent ECMO from January 2009 to December 2016 were retrospectively analyzed for BSI episodes at a 2,700-bed, tertiary center. Epidemiological and clinical characteristics and outcomes of BSI were evaluated and were compared for etiologic groups (gram-positive cocci, gram-negative rods, and fungi groups). Risk factors for 14-day mortality were analyzed.

Results: A total of 1,100 patients underwent ECMO during the study period, and 65 BSI episodes occurred in 61 patients. The BSI incidence was 8.3 episodes/1,000 ECMO days, which significantly decreased over time ( = 0.03), primarily in gram-positive cocci BSI. Gram-positive cocci, gram-negative rods, and fungi accounted for 38%, 40%, and 22% of the 73 blood isolates, respectively. Baseline characteristics were comparable between groups. Catheter-related infection (CRI) and pneumonia were the most common sources of BSI; 52% of gram-positive cocci BSIs and 79% of fungi BSIs were caused by CRI, and 75% of gram-negative BSIs by pneumonia. Patients with gram-negative rods BSI died more frequently and earlier than those with other BSIs. Independent risk factors for 14-day mortality were older age and gram-negative rods BSI.

Conclusions: The decreased BSI incidence during ECMO was mainly because of the decrease of gram-positive cocci BSI. The high early mortality of gram-negative rods BSI makes prevention and adequate treatment necessary.
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http://dx.doi.org/10.1177/0885066620985538DOI Listing
December 2020

Kinetics of Serological Response in Patients with Severe Fever with Thrombocytopenia Syndrome.

Viruses 2020 12 25;13(1). Epub 2020 Dec 25.

Department of Microbiology, Korea University College of Medicine, Seongbuk-gu, Seoul 02841, Korea.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV). We investigated the detailed kinetics of serologic response in patients with SFTS. Twenty-eight patients aged ≥18 years were enrolled between July 2015 and October 2018. SFTS was confirmed by detecting SFTSV RNA in their plasma using reverse transcription polymerase chain reaction. SFTSV-specific IgG and IgM were measured using immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA). We found that SFTSV-specific IgG was detected at days 5-9 after symptom onset, and its titer was rising during the course of disease. SFTSV-specific IgM titer peaked at around week 2-3 from symptom onset. The SFTSV-specific seropositive rates for days 5-9, 10-14, 15-19, and 20-24 from symptom onset using IFA and ELISA were 63%, 76%, 90%, and 100%, and 58%, 86%, 100%, and 100%, respectively, for IgG, whereas they were 32%, 62%, 80%, and 100%, and 53%, 62%, 70%, and 100%, respectively, for IgM. The delayed IgM response could be attributed to the low sensitivity of SFTSV-specific IgM IFA or ELISA and/or impaired immune responses. The IgM test using IFA or ELISA that we used in this study is, therefore, insufficient for the early diagnosis of SFTS.
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http://dx.doi.org/10.3390/v13010006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823500PMC
December 2020

Weak Closed-Loop Vibrational Stimulation Improves the Depth of Slow-wave Sleep and Declarative Memory Consolidation.

Sleep 2020 Dec 25. Epub 2020 Dec 25.

Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University, Seoul 03080, Republic of Korea.

Sleep is a unique behavioral state that affects body functions and memory. Although previous studies suggested stimulation methods to enhance sleep, a new method is required that is practical for long-term and unconstrained use by people. In this study, we used a novel closed-loop vibration stimulation method that delivers stimulus in interaction with the intrinsic heart rhythm and examined the effects of stimulation on sleep and memory. Twelve volunteers participated in the experiment and each underwent one adaptation night and two experimental conditions-a stimulation condition (STIM) and no-stimulation condition (SHAM). The heart rate variability analysis showed a significant increase in the nHF and the nLF significantly decreased under the STIM during the slow-wave sleep (SWS) stage. Furthermore, the synchronization ratio between the heartbeat and the stimulus significantly increased under the STIM in the SWS stage. From the electroencephalogram (EEG) spectral analysis, EEG relative powers of slow-wave activity and theta frequency bands showed significant increase during the STIM in the SWS stage. Additionally, the memory retention significantly increased under the STIM compared to the SHAM. These findings suggest that the closed-loop stimulation improves the SWS-stage depth and memory retention, and further provides a new technique for sleep enhancement.
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http://dx.doi.org/10.1093/sleep/zsaa285DOI Listing
December 2020

Severe Human Bocavirus-Associated Pneumonia in Adults at a Referral Hospital, Seoul, South Korea.

Emerg Infect Dis 2021 Jan;27(1):226-228

We report a case series of severe human bocavirus-associated pneumonia in adults in Seoul, South Korea. The virus accounted for 0.5% of all severe pneumonia cases. Structural lung disease and hematologic malignancy were common underlying diseases. Overall death rate was 54.5%. Higher death rates were associated with co-infection (83.3%) and immunocompromise (80.0%).
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http://dx.doi.org/10.3201/eid2701.202061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774574PMC
January 2021

In Vitro Activities and Inoculum Effects of Ceftazidime-Avibactam and Aztreonam-Avibactam against Carbapenem-Resistant Isolates from South Korea.

Antibiotics (Basel) 2020 Dec 15;9(12). Epub 2020 Dec 15.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Ceftazidime-avibactam (CAZ-AVI) and aztreonam-avibactam (AZT-AVI) are novel antibiotic combinations active against multidrug-resistant Gram-negative pathogens. This study aimed to evaluate their in vitro activities and inoculum effects in carbapenem-resistant (CRE), including carbapenemase-producing (CP)-CRE and non-CP-CRE. A total of 81 independent clinical isolates of carbapenem-resistant and were collected. CAZ-AVI and AZT-AVI minimal inhibitory concentrations (MICs) were evaluated by broth microdilution using standard and high inocula. The inoculum effect was defined as an ≥8-fold increase in MIC with high inoculum. Phenotypic determination of β-lactam resistance mechanism and PCR for carbapenemase genes were performed. Of the 81 CRE isolates, 35 (43%) were CP-CRE. Overall, 73% of the isolates were susceptible to CAZ-AVI, and 95% had low AZT-AVI MICs (≤8 µg/mL). The MICMICs of CAZ-AVI and AZT-AVI were 4/≥512 µg/mL and 0.5/4 µg/mL, respectively. CAZ-AVI was more active against non-CP-CRE than against CP-CRE (susceptibility 80% vs. 63%, = 0.08; MIC/MIC, 2/16 μg/mL vs. 4/≥512 μg/mL), whereas AZT-AVI was more active against CP-CRE (MIC/MIC, 0.25/1 μg/mL vs. 0.5/8 μg/mL). All four isolates with high AZT-AVI MIC (≥16 μg/mL) were resistant to CAZ-AVI, but only 18% (4/22) of CAZ-AVI-resistant isolates had high AZT-AVI MIC. The rates of the inoculum effect for CAZ-AVI and AZT-AVI were 18% and 47%, respectively ( < 0.001). Interestingly, the frequency of the AZT-AVI inoculum effect was higher in than (64% vs. 8%, < 0.001). AZT-AVI is more active against CRE than CAZ-AVI, even in CP-CRE and CAZ-AVI-resistant isolates. The presence of a substantial inoculum effect may contribute to clinical failure in high-inoculum infections treated with AZT-AVI.
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http://dx.doi.org/10.3390/antibiotics9120912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765481PMC
December 2020

Characterization of bacteriophage VVP001 and its application for the inhibition of Vibrio vulnificus causing seafood-borne diseases.

Food Microbiol 2021 Apr 29;94:103630. Epub 2020 Aug 29.

Department of Food Science and Biotechnology, Graduate School of Biotechnology, Kyung Hee University, Yongin 17104, Republic of Korea; Department of Agricultural Biotechnology, Center for Food Safety and Toxicology, And Center for Food and Bioconvergence, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:

Vibrio vulnificus is a major food-borne pathogen that causes septicemia and cellulitis with a mortality rate of >50%. However, there are no efficient natural food preservatives or biocontrol agents to control V. vulnificus in seafood. In this study, we isolated and characterized a novel bacteriophage VVP001. Host range and transmission electron microscopy morphology observations revealed that VVP001 belongs to the family Siphoviridae and specifically infects V. vulnificus. Phage stability tests showed that VVP001 is stable at a broad temperature range of -20 °C to 65 °C and a pH range from 3 to 11, which are conditions for food applications (processing, distribution, and storage). In vitro challenge assays revealed that VVP001 inhibited V. vulnificus MO6-24/O (a clinical isolate) growth up to a 3.87 log reduction. In addition, complete genome analysis revealed that the 76 kb VVP001 contains 102 open reading frames with 49.64% G + C content and no gene encoding toxins or other virulence factors, which is essential for food applications. Application of VVP001 to fresh abalone samples contaminated with V. vulnificus demonstrated its ability to inhibit V. vulnificus growth, and an in vivo mouse survival test showed that VVP001 protects mice against high mortality (survival rate >70% at a multiplicity of infection of 1000 for up to 7 days). Therefore, the bacteriophage VVP001 can be used as a good natural food preservative and biocontrol agent for food applications.
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http://dx.doi.org/10.1016/j.fm.2020.103630DOI Listing
April 2021

Association of heart rate variability with REM sleep without atonia in idiopathic REM sleep behavior disorder.

J Clin Sleep Med 2021 Mar;17(3):461-469

Department of Psychiatry and Center for Sleep and Chronobiology, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea.

Study Objectives: Idiopathic rapid eye movement sleep behavior disorder (iRBD), characterized by rapid eye movement sleep without atonia (RSWA) and dream-enactment behavior, has been suggested to be a predictor of α-synucleinopathies. Autonomic instability, represented by heart rate variability, is a common characteristic of both iRBD and α-synucleinopathies. Previous studies reported that RSWA was associated with autonomic dysfunction and was a possible predictor of phenoconversion. Therefore, we sought to compare heart rate variability between iRBD and control groups and explore the relationship between heart rate variability and RSWA in patients with iRBD.

Methods: Nocturnal polysomnographic data on 47 patients (28 men, 19 women) diagnosed with iRBD based on video-polysomnography and 26 age-matched and sex-matched controls were reviewed. The first 5-minute epoch with a stable electrocardiogram lead II on video-polysomnography was selected from stage N2, wake, and rapid eye movement. For quantification of RSWA, tonic activity was analyzed from the submentalis electromyogram and phasic activity from the submentalis and bilateral anterior tibialis electromyogram channels.

Results: Compared to the control group, the iRBD group showed significant reductions in the standard deviation of the R-R intervals, the root mean square of successive R-R interval differences, and high-frequency values. Quantified tonic activity was inversely correlated with normalized low-frequency values and low-frequency/high-frequency ratios and positively correlated with normalized high-frequency values.

Conclusions: This study implied decreased cardiac autonomic function in patients with iRBD, which showed parasympathetic predominance. Heart rate variability of the patients with iRBD in this study was associated with quantified tonic RSWA, which was previously reported to be a possible predictor of phenoconversion.
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http://dx.doi.org/10.5664/jcsm.8934DOI Listing
March 2021

Phenotypic Discovery of an Antivirulence Agent against via Modulation of Quorum-Sensing Regulator SmcR.

ACS Infect Dis 2020 11 21;6(11):3076-3082. Epub 2020 Oct 21.

CRI Center for Chemical Proteomics, Department of Chemistry, Seoul National University, Seoul 08826, Korea.

An antivirulence agent against named quoromycin (QM) was discovered by a phenotype-based elastase inhibitor screening. Using the fluorescence difference in two-dimensional gel electrophoresis (FITGE) approach, SmcR, a quorum-sensing master regulator and homologue of LuxR, was identified as the target protein of QM. We confirmed that the direct binding of QM to SmcR inhibits the quorum-sensing signaling pathway by controlling the DNA-binding affinity of SmcR and thus effectively alleviates the virulence of and . QM can be regarded as a novel antivirulence agent for the treatment of infection.
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http://dx.doi.org/10.1021/acsinfecdis.0c00587DOI Listing
November 2020

Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients With Carbapenem-Resistant Bacteremia.

Open Forum Infect Dis 2020 Oct 24;7(10):ofaa378. Epub 2020 Aug 24.

Departments of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: Carbapenem-resistant (CRAB) infection is associated with significant mortality, causing worldwide concern, yet there are limited data on contributing microbiological factors. This study aimed to identify the clinical and microbiologic risk factors for mortality in CRAB bacteremia.

Methods: Adult patients with monomicrobial CRAB bacteremia in a 2700-bed tertiary hospital between December 2012 and December 2018 were retrospectively enrolled. Risk factors for 30-day mortality were evaluated. All isolates collected on the first day of bacteremia were subjected to colistin susceptibility testing by broth microdilution and to genotyping by multilocus sequence typing.

Results: A total of 164 patients were enrolled, and 90 (55%) died within 30 days. The most common genotype among the isolates was ST191 (49%), and 12 isolates (7%) were resistant to colistin. Genotype, colistin minimum inhibitory concentration, and colistin resistance were not significantly associated with mortality, in contrast to several clinical factors. In multivariable analysis, ineradicable or not-eradicated focus (adjusted odds ratio [aOR], 4.92; 95% CI, 1.95-12.42; = .001), septic shock (aOR, 4.72; 95% CI, 2.12-10.49; < .001), and inappropriate antimicrobial therapy (aOR, 2.54; 95% CI, 1.05-6.16; = .04) were independent risk factors for mortality. Among antibiotic strategies, colistin combined with tigecycline or other antibiotics were significantly associated with lower mortality after adjustment for confounding factors.

Conclusions: Clinical factors such as the nature of the infection source and source control, severity of bacteremia, and appropriateness of antibiotics, rather than microbiological factors, contribute to mortality in CRAB bacteremia. A specific antibiotic combination may help improve outcomes.
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http://dx.doi.org/10.1093/ofid/ofaa378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539690PMC
October 2020

Comparison of clinical outcomes of patients infected with KPC- and NDM-producing Enterobacterales: a retrospective cohort study.

Clin Microbiol Infect 2020 Sep 30. Epub 2020 Sep 30.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: We aimed to compare clinical outcomes of patients with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales and those with New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales.

Methods: We performed a retrospective cohort study of all adult patients with KPC- or NDM-producing Enterobacterales isolates in a 2700-bed tertiary referral hospital in Seoul, South Korea, between 2010 and 2019. The primary outcome was 30-day mortality after first isolation of KPC- or NDM-producing Enterobacterales. The secondary outcome was the development of infection within 30 days by the colonizing isolates, among colonized patients. We performed Cox regression analysis for 30-day mortality and competing risk analysis for development of infection.

Results: A total of 859 patients were identified during the study period; 475 (55%) had KPC and 384 (45%) had NDM. Thirty-day mortality was significantly higher in the KPC group than in the NDM group (17% (81/475) vs 9% (33/384); p < 0.001). The KPC group developed infection within 30 days from the initial colonization after first isolation more frequently than the NDM group (8% (27/353) vs. 3% (10/295); p 0.02). Multivariable analysis revealed that independent risk factors for 30-day mortality were solid cancer (adjusted hazard ratio (aHR) 2.51; 95% confidence interval (CI) 1.66-3.79; p < 0.001), solid organ transplant (aHR 0.32; 95% CI 0.17-0.61; p < 0.001), a high APACHE II score (aHR 1.11; 95% CI 1.08-1.13; p < 0.001), KPC-producing Enterobacterales (aHR 1.69; 95% CI 1.02-2.79; p 0.04), previous carbapenem use within 3 months (aHR 1.86; 95% CI 1.26-2.75; p < 0.001) and site of KPC- or NDM-producing Enterobacterales infection at the time of the first culture (p < 0.001).

Discussion: Our study suggests that KPC-producing Enterobacterales is significantly associated with poorer outcomes than NDM-producing Enterobacterales.
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http://dx.doi.org/10.1016/j.cmi.2020.09.043DOI Listing
September 2020

Frequency of and risk factors for reversion of QuantiFERON test in healthcare workers in an intermediate-tuberculosis burden country.

Clin Microbiol Infect 2020 Sep 21. Epub 2020 Sep 21.

Office for Infection Control, Asan Medical Center, Seoul, Republic of Korea; Departments of Infectious Diseases, and. Electronic address:

Objectives: High risk healthcare workers (HCWs) are often screened for latent tuberculosis infection (LTBI) using QuantiFERON tests (QFTs), with annual serial tests often showing reversion from positive to negative results. We assessed the frequency of and risk factors for reversion of QFTs in HCWs in an intermediate-tuberculosis burden country.

Methods: We enrolled high risk HCWs at a tertiary-care hospital in South Korea, who were assessed by QFTs at least twice between 2017 and 2019.

Results: Of the 1,870 HCWs screened, 1,542 (82%) had persistent negative results, 229 (12%) had persistent positive results, 53 (3%) showed reversion, and 46 (2%) showed conversion from negative to positive. Multivariate analysis comparing the characteristics of the 229 HCWs with persistent positive results and the 53 who experienced reversion showed that older age (adjusted odds ratio [aOR]: 0.96; 95% CI: 0.92-0.99), male sex (aOR: 0.29; 95% CI: 0.11-0.78) and high (≥0.70 IU/ml) baseline QFT results (aOR: 0.15; 95% CI: 0.07-0.31) were inversely associated with reversion. Using a ROC curve-derived cut-off of < 0.738 IU/ml, the area under the curve was 0.79. Of 53 HCWs with reversion, 36 (78%) had below 0.738 IU/mL of baseline QFT, while 181 (79%) of 229 HCWs without reversion had above 0.738 IU/mL of baseline QFT.

Conclusion: Reversion during serial testing is unlikely in HCWs who are male, older in age, and have higher baseline QFT results. Serial testing without LTBI treatment may be indicated in HCWs who are female, younger, and, especially, have lower QFT results.
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http://dx.doi.org/10.1016/j.cmi.2020.09.016DOI Listing
September 2020

Molecular interaction between methicillin-resistant Staphylococcus aureus (MRSA) and chicken breast reveals enhancement of pathogenesis and toxicity for food-borne outbreak.

Food Microbiol 2021 Feb 24;93:103602. Epub 2020 Jul 24.

National Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, And Center for Food Safety and Toxicology, Seoul National University, Seoul, 08826, South Korea; Food-borne Pathogen Omics Research Center (FORC), Seoul National University, Seoul, 08826, South Korea. Electronic address:

To study pathogenesis and toxicity of Staphylococcus aureus in foods, FORC_062 was isolated from a human blood sample and complete genome sequence has a type II SCCmec gene cluster and a type II toxin-antitoxin system, indicating an MRSA strain. Its mobile gene elements has many pathogenic genes involved in host infection, biofilm formation, and various enterotoxin and hemolysin genes. Clinical MRSA is often found in animal foods and ingestion of MRSA-contaminated foods causes human infection. Therefore, it is very important to understand the role of contaminated foods. To elucidate the interaction between clinical MRSA FORC_062 and raw chicken breast, transcriptome analysis was conducted, showing that gene expressions of amino acid biosynthesis and metabolism were specifically down-regulated, suggesting that the strain may import and utilize amino acids from the chicken breast, but not able to synthesize them. However, toxin gene expressions were up-regulated, suggesting that human infection of S. aureus via contaminated food may be more fatal. In addition, the contaminated foods enhance multiple-antibiotic resistance activities and virulence factors in this clinical MRSA. Consequently, MRSA-contaminated food may play a role as a nutritional reservoir as well as in enhancing factor for pathogenesis and toxicity of clinical MRSA for severe food-borne outbreaks.
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http://dx.doi.org/10.1016/j.fm.2020.103602DOI Listing
February 2021

Comparison of the characteristics of patients with invasive infections and noninvasive infections caused by Trichosporon asahii.

Med Mycol 2020 Sep 2. Epub 2020 Sep 2.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

We performed retrospective study to identify the characteristics of invasive Trichosporon asahii infection. A total of 102 patients with T. asahii were identified including 18 (18%) with invasive infection. Invasive infection was associated with indwelling central venous catheter (94% vs 54%, P = .001), prior antifungal agent use (50% vs 18%, P = .01), hematologic malignancy (33% vs 7%, P = .006), and end-stage renal disease (28% vs 7%, P = .02). Patients with invasive infections had higher in-hospital mortality than patients with noninvasive infections (61% vs 27%, P = .006). Those with the above risk factors should be monitored for the development of invasive T. asahii infection.

Lay Summary: Patients with indwelling central venous catheter, prior antifungal agent use, hematologic malignancy, and end-stage renal disease were associated with invasive Trichosporon asahii infection. Patients with invasive infections had higher in-hospital mortality than patients without invasive infection.
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http://dx.doi.org/10.1093/mmy/myaa076DOI Listing
September 2020

Analysis of Microbiota Structure and Potential Functions Influencing Spoilage of Fresh Beef Meat.

Front Microbiol 2020 22;11:1657. Epub 2020 Jul 22.

Department of Life Science, Multidisciplinary Genome Institute, Hallym University, Chuncheon, South Korea.

Beef is one of the most consumed food worldwide, and it is prone to spoilage by bacteria. This risk could be caused by resident microbiota and their alterations in fresh beef meat during processing. However, scarce information is available regarding potential spoilage factors due to resident microbiota in fresh beef meat. In this study, we analyzed the microbiota composition and their predicted functions on fresh beef meat. A total of 120 beef meat samples (60 fresh ground and 60 non-ground beef samples) were collected from three different sites in South Korea on different months, and the microbiota were analyzed by the MiSeq system. Our results showed that although the microbiota in beef meat were varied among sampling site and months, the dominant phyla were the same with shared core bacteria. Notably, psychrotrophic genera, related to spoilage, were detected in all samples, and their prevalence increased significantly in July. These genera could inhibit the growth of other microbes with using glucose by fermentation. The results of this study extend our understanding of initial microbiota in fresh beef meat and potential functions influencing spoilage and can be useful to develop the preventive measures to reduce the spoilage of beef meat products.
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http://dx.doi.org/10.3389/fmicb.2020.01657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387507PMC
July 2020

Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bacteremia.

Int J Antimicrob Agents 2020 Oct 2;56(4):106126. Epub 2020 Aug 2.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: The aims of this study were to identify whether the site of acquisition or the underlying carbapenem-resistant Enterobacteriaceae (CRE) resistance mechanism was associated with clinical outcomes, and to evaluate risk factors for 14-day mortality in patients with CRE bacteremia.

Materials And Methods: A retrospective cohort study was conducted at a 2700-bed tertiary center. All adult patients with monomicrobial carbapenem-resistant Escherichia coli or Klebsiella pneumoniae bacteremia from 2011 to 2018 were included. All blood isolates collected were tested with a modified carbapenem inactivation method for phenotypic detection of carbapenemase.

Results: Of 133 patients with monomicrobial CRE bacteremia, 63 (47.4%) were infected with carbapenemase-producing CRE (CP-CRE), and 70 (52.6%) with non-CP-CRE. Patients with community-onset infection (COI) were more likely to present with biliary or urinary tract infections, less likely to have ineradicable or non-eradicated foci and to receive appropriate empirical therapy, and marginally more likely to have CP-CRE compared with those with hospital-acquired infection (HAI). However, 14-day mortality was significantly lower in COI than HAI (7% vs 29%, P = 0.01). Patients who died were more likely to have had a higher APACHE II score, ineradicable or non-eradicated foci, and a lower chance of having received appropriate antibiotic treatment. Multivariate analysis revealed that HAI, high APACHE II score, and inappropriate antibiotic treatment were independent risk factors for mortality. Carbapenemase production did not affect mortality.

Conclusions: The results of this study indicate that timely, appropriate treatment is essential for managing CRE bacteremia, regardless of carbapenemase production, particularly in critically ill patients with hospital-acquired bacteremia.
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http://dx.doi.org/10.1016/j.ijantimicag.2020.106126DOI Listing
October 2020

Decreased Incidence of Methicillin-Resistant Staphylococcus aureus Bacteremia in Intensive Care Units: a 10-Year Clinical, Microbiological, and Genotypic Analysis in a Tertiary Hospital.

Antimicrob Agents Chemother 2020 09 21;64(10). Epub 2020 Sep 21.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

There are limited long-term data on the trends in incidence and characteristics of methicillin-resistant (MRSA) bacteremia (MRSAB) in intensive care units (ICUs) in which infection control measures have been adopted. We evaluated the trend of incidence and changes in characteristics of MRSA bacteremia in ICUs at a tertiary-care hospital over 10 years using prospective cohort data. ICU-acquired bacteremia was defined as bacteremia (SAB) that occurred 48 h or more after ICU admission. MRSA isolates were collected and subjected to microbiological and genotypic analyses. A total of 529 SAB episodes were identified among 367,175 ICU patients. Of these episodes, 288 (54.4%) were ICU acquired, 238 (82.6%) of which were MRSAB. The incidence density of ICU-acquired MRSAB decreased from 1.32 per 1,000 patient-days to 0.19 per 1,000 patient-days (a decrease of 20% annually; 0.001 for trend), whereas that of non-ICU-acquired MRSAB fluctuated and did not decrease significantly. The decline in ICU-acquired MRSAB was due to lower catheter-related infection and less pneumonia. Rates of persistent bacteremia and 12-week mortality also fell significantly. A total of 183 isolates were collected from 238 ICU-acquired MRSAB cases. There were no significant changes in the geometric means of vancomycin MICs, vancomycin heteroresistance, or the sequence types of MRSA isolates over time. Chlorhexidine MICs decreased (0.001 for trend) in association with a decline in frequency of the or gene that was related to reductions in specific types. The incidence of MRSAB in ICUs has decreased dramatically over time, but most of the microbiological and genotypic characteristics of MRSA isolates have not changed.
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http://dx.doi.org/10.1128/AAC.01082-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508613PMC
September 2020

A MARTX Toxin Gene Is Controlled by Host Environmental Signals through a CRP-Coordinated Regulatory Network in Vibrio vulnificus.

mBio 2020 07 28;11(4). Epub 2020 Jul 28.

National Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea

A multifunctional autoprocessing repeats-in-toxin (MARTX) toxin plays an essential role in the virulence of many pathogens, including a fulminating human pathogen H-NS and HlyU repress and derepress expression of the MARTX toxin gene in , respectively. However, little is known about other regulatory proteins and environmental signals involved in regulation. In this study, we found that a leucine-responsive regulatory protein (Lrp) activates by binding directly and specifically to the promoter, P Phased hypersensitivity resulting from DNase I cleavage of the P regulatory region suggests that Lrp probably induces DNA bending in P Lrp activates P independently of H-NS and HlyU, and leucine inhibits Lrp binding to P and reduces the Lrp-mediated activation. Furthermore, a cyclic AMP receptor protein (CRP) represses P , and exogenous glucose relieves the CRP-mediated repression. Biochemical and mutational analyses demonstrated that CRP binds directly and specifically to the upstream region of P , which presumably alters the DNA conformation in P and thus represses Moreover, CRP represses expression of and by binding directly to their upstream regions, forming coherent feed-forward loops with Lrp and HlyU. In conclusion, expression of is controlled by a regulatory network comprising CRP, Lrp, H-NS, and HlyU in response to changes in host environmental signals such as leucine and glucose. This collaborative regulation enables the elaborate expression of , thereby enhancing the fitness and pathogenesis of during the course of infection. A MARTX toxin, RtxA, is an essential virulence factor of many pathogens, including species. H-NS and HlyU repress and derepress, respectively, expression of a life-threatening pathogen, We found that Lrp directly activates independently of H-NS and HlyU, and leucine inhibits the Lrp-mediated activation of Furthermore, we demonstrated that CRP represses but derepresses in the presence of exogenous glucose. CRP represses not only directly by binding to upstream of but also indirectly by repressing and This is the first report of a regulatory network comprising CRP, Lrp, H-NS, and HlyU, which coordinates the expression in response to environmental signals such as leucine and glucose during infection. This elaborate regulatory network will enhance the fitness of and contribute to its successful infection within the host.
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http://dx.doi.org/10.1128/mBio.00723-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387792PMC
July 2020

Clinical characteristics and prognostic factors of extraintestinal infection caused by Clostridioides difficile: analysis of 60 consecutive cases.

Eur J Clin Microbiol Infect Dis 2020 Nov 6;39(11):2133-2141. Epub 2020 Jul 6.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul, 05505, Republic of Korea.

Data regarding extraintestinal Clostridioides difficile infections (ECDIs) remain scarce and anecdotal. We conducted a retrospective cohort study to investigate characteristics and prognostic factors in patients with ECDI. From January 1997 through December 2018, 60 patients were enrolled and divided into three groups as follows: group A (gastrointestinal [GI] disruption caused by malignancy, n = 13); group B (GI disruption from causes other than malignancy, n = 25); group C (no GI disruption, n = 22). GI disruption was defined as compromised integrity of the GI tract caused by abdominal surgery, perforation, malignancy, enterocolitis, or bleeding. The incidence of ECDI was 2.53 per 100,000 admissions. The most common specimens yielded C. difficile were blood (36.7%), peritoneal fluid (20.0%), and abscesses (16.7%). Six patients (10.0%) had confirmed C. difficile enterocolitis, and 36 patients (60.0%) had a polymicrobial infection. C. difficile bacteremia was significantly more common in group A patients than those in groups B or C (53.8% vs. 48.0% vs. 13.6%, p = 0.02), as was the 30-day mortality rate (69.2% vs. 12.0% vs. 18.2%, respectively; p < 0.001). In multivariate analysis, group A (adjusted odds ratio [aOR], 17.32; 95% confidence interval [CI], 2.96-101.21; p = 0.002) and an age of > 65 years (aOR, 7.09; 95% CI, 1.31-38.45; p = 0.02) were independent risk factors for 30-day mortality. ECDI was uncommonly associated with C. difficile enterocolitis. Two factors, GI disruption caused by malignancy, and old age, were associated with significantly poorer short-term outcomes.
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http://dx.doi.org/10.1007/s10096-020-03975-9DOI Listing
November 2020

Association of herpes zoster with dementia and effect of antiviral therapy on dementia: a population-based cohort study.

Eur Arch Psychiatry Clin Neurosci 2020 Jul 1. Epub 2020 Jul 1.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro-43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

We investigated the association between herpes zoster (HZ) and dementia, and the effects of antiviral therapy on the risk of dementia. We used the National Health Insurance Service-National Sample Cohort in South Korea to identify individuals that were followed from January 1, 2002, to December 31, 2013. Occurrences of HZ and dementia were identified using the relevant diagnostic codes. Dementia was defined as the presence of diagnostic codes and history of anti-dementia drug prescription. Propensity score matching (1:1) was carried out among HZ patients according to antiviral therapy. A total of 229,594 individuals aged ≥50 years were analyzed. The incidences of the first-diagnosed HZ and dementia were 16.69 and 4.67 per 1000 person-years (PY), respectively. HZ patients had a higher risk of dementia (incidence rate ratio [IRR], 1.94 [95% CI 1.83-2.06]; adjusted hazard ratio [HR], 1.12 [95% CI 1.05-1.19]). Of the 34,505 patients with HZ, 28,873 (84%) had received antiviral treatment. The crude incidence rates of subsequent dementia in the treated and untreated groups were 7.79 and 12.27 per 1000 PY, respectively, resulting in an IRR of 0.64 (95% CI 0.56-0.72) and covariate-adjusted HR of 0.79 (95% CI 0.69-0.90). After propensity score matching, the treated group showed a significantly lower risk of dementia (HR 0.76; 95% CI 0.65-0.90). In this large population-based cohort study, HZ was associated with a higher risk of dementia. The use of antiviral agents in HZ patients was associated with lower risks of dementia.
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http://dx.doi.org/10.1007/s00406-020-01157-4DOI Listing
July 2020

The usefulness of quantitative interferon-gamma releasing assay response for predicting active tuberculosis in kidney transplant recipients: A quasi-experimental study.

J Infect 2020 09 29;81(3):403-410. Epub 2020 Jun 29.

Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Objectives: We evaluated the effectiveness of IGRA-based isoniazid (INH) treatment with the diagnostic value of quantitative IGRA titer for post-transplant tuberculosis (TB) in kidney transplant (KT) recipients.

Methods: All adult KT recipients were enrolled from January 2014 to December 2017. The development of TB after KT was observed, stratified by quantitative IGRA results as well as by IGRA results with/without INH treatment.

Results: Of 1150 KT recipients, 322 (28%) revealed positive IGRA results (≥0.35 IU/mL) and 12 (1.0%) developed TB. Seven (3.2%) of 217 patients with positive IGRA without INH developed TB, whereas none of 105 patients with positive IGRA with INH developed TB (rate difference -1616 per 100,000 person-years, P = 0.016) and 5 (0.6%) of 828 patients with negative or indeterminate IGRA developed TB (rate difference -1388 per 100,000 person-years, P<0.001). Among the 217 positive IGRA patients without INH, 6 (6.4%) of 94 patients who had positive IGRA titer>2.96 IU/mL developed TB, whereas one (0.8%) of 123 patients who had positive IGRA titer≤2.96 IU/mL developed TB (rate difference 2964 per 100,000 person-years, P = 0.017).

Conclusions: IGRA-based INH treatment with risk stratification by quantitative IGRA results appears to be effective to prevent the development of TB in KT recipients.
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http://dx.doi.org/10.1016/j.jinf.2020.06.070DOI Listing
September 2020

Clinical characteristics and outcomes of Staphylococcus aureus bacteremia from a biliary source.

Eur J Clin Microbiol Infect Dis 2020 Oct 15;39(10):1951-1957. Epub 2020 Jun 15.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Staphylococcus aureus is a virulent gram-positive organism, which rarely involves the biliary tract. This study aimed to analyze the clinical characteristics and outcomes of S. aureus bacteremia (SAB) originating from the biliary tract by comparing them with those of catheter-related SAB and biliary Klebsiella pneumoniae bacteremia. A matched case-control study within a prospective observational cohort of patients with SAB was conducted. Biliary SAB was defined as the isolation of S. aureus from blood cultures with symptoms and signs of biliary infection. Biliary SAB patients were matched (1:3) with the control groups: patients with catheter-related SAB and biliary Klebsiella pneumoniae bacteremia. Out of 1818 patients with SAB enrolled in the cohort, 42 (2%) had biliary SAB. Majority of these patients had solid tumors involving the pancreaticobiliary tract or liver, biliary drainage stent, and/or recent broad-spectrum antibiotic exposure. Patients with biliary SAB were more likely to have community-onset SAB, solid tumors, and lower APACHE II score than those with catheter-related SAB. They were less likely to have community-acquired infection and solid tumors and more likely to have lower Charlson comorbidity index and higher APACHE II score as compared with biliary K. pneumoniae bacteremia. The 12-week mortality in the biliary SAB group was higher than those in other control groups (60% vs. 20% and 14%). After adjusting for confounding factors, biliary SAB was independently associated with higher mortality. Biliary SAB is relatively rare. When it is clinically suspected, early aggressive treatment should be considered due to high mortality.
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http://dx.doi.org/10.1007/s10096-020-03940-6DOI Listing
October 2020

Update: Radiographic and CT Features of Viral Pneumonia.

Radiographics 2020 Jul-Aug;40(4):E8-E15. Epub 2020 Jun 5.

From the Department of Radiology and Research Institute of Radiology (H.J.K., J.C., K.H.D.), Division of Infectious Disease, Department of Internal Medicine (S.H.C.), and Department of Laboratory Medicine (H.S.), Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, South Korea.

.-Articles in the Update section provide current knowledge to supplement or update information found in full-length articles previously published in . Authors of the previously published article provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes. Articles in this section are published solely online and are linked to the original article.
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http://dx.doi.org/10.1148/rg.2020200097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336757PMC
June 2020

Immunodeficiency risk score for prediction of mortality by parainfluenza virus infection in patients with hematologic malignancy.

Ann Hematol 2020 Jun 7;99(6):1231-1239. Epub 2020 May 7.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Parainfluenza virus (PIV) infection is a significant cause of morbidity and mortality, especially in hematologic malignancy patients including hematopoietic stem cell transplantation (HCT) recipients. However, limited information is available for risk stratification in PIV-infected patients with hematologic malignancy with or without HCT. Patients with hematologic malignancy diagnosed with PIV from January 2009 to December 2018 were retrospectively included in a tertiary care hospital in Seoul, South Korea. Upper respiratory tract infection (URTI) was defined as the detection of PIV in a nasopharyngeal sample with URTI symptoms without new pulmonary infiltrates. Lower respiratory tract infection (LRTI) was defined as detection of PIV in either upper or lower respiratory tract samples with new pulmonary infiltrates, with or without hypoxia. PIV-associated mortality was defined as death with respiratory failure and persistent LRTI within 90 days after diagnosis. The study included 143 adult patients. Of these, 55 (38%) progressed to or initially presented with LRTI. Among these, 22 (40%) died from PIV-associated mortality. An immunodeficiency risk score was developed from associated risk factors using a multivariable Cox regression model. Patients were stratified into low (0-2), moderate (3-5), and high risk (6-8) groups with PIV-associated mortalities of 0%, 9%, and 67%, respectively (p < 0.005, Harrell's C-index = 0.84). PIV infection can result in substantial mortality in patients with hematologic malignancy if it progresses to LRTI. The immunodeficiency risk score presented here may be useful for distinguishing moderate and high risk groups that might benefit from antiviral therapy.
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http://dx.doi.org/10.1007/s00277-020-03996-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203544PMC
June 2020

Long-distance aberrant heterotopic connectivity in a mouse strain with a high incidence of callosal anomalies.

Neuroimage 2020 08 23;217:116875. Epub 2020 Apr 23.

Post-Graduate Program in Morphological Sciences, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil; D'Or Institute Research and Education (IDOR), Brazil; National Center of Structural Biology and Bioimaging (CENABIO), Federal University of Rio de Janeiro, Brazil. Electronic address:

Corpus callosum dysgenesis (CCD) is a developmental brain condition in which some white matter fibers fail to find their natural course across the midplane, reorganizing instead to form new aberrant pathways. This type of white matter reorganization is known as long-distance plasticity (LDP). The present work aimed to characterize the Balb/c mouse strain as a model of CCD. We employed high-resolution anatomical MRI in 81 Balb/c and 27 C57bl6 mice to show that the Balb/c mouse strain presents a variance in the size of the CC that is 3.9 times higher than the variance of normotypical C57bl6. We also performed high-resolution diffusion-weighted imaging (DWI) in 8 Balb/c and found that the Balb/c strain shows aberrant white matter bundles, such as the Probst (5/8 animals) and the Sigmoid bundles (7/8 animals), which are similar to those found in humans with CCD. Using a histological tracer technique, we confirmed the existence of these aberrant bundles in the Balb/c strain. Interestingly, we also identified sigmoid-like fibers in the C57bl6 strain, thought to a lesser degree. Next, we used a connectome approach and found widespread brain connectivity differences between Balb/c and C57bl6 strains. The Balb/c strain also exhibited increased variability of global connectivity. These findings suggest that the Balb/c strain presents local and global changes in brain structural connectivity. This strain often presents with callosal abnormalities, along with the Probst and the Sigmoid bundles, making it is an attractive animal model for CCD and LDP in general. Our results also show that even the C57bl6 strain, which typically serves as a normotypical control animal in a myriad of studies, presents sigmoid-fashion pattern fibers laid out in the brain. These results suggest that these aberrant fiber pathways may not necessarily be a pathological hallmark, but instead an alternative roadmap for misguided axons. Such findings offer new insights for interpreting the significance of CCD-associated LDP in humans.
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http://dx.doi.org/10.1016/j.neuroimage.2020.116875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590260PMC
August 2020

Influence of pathogen contamination on beef microbiota under different storage temperatures.

Food Res Int 2020 06 20;132:109118. Epub 2020 Feb 20.

Department of Agricultural Biotechnology, Center for Food Safety and Toxicology, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:

Outbreaks of food poisoning due to the consumption of contaminated beef from fast-food chains are becoming more frequent. Pathogen contamination in beef influences its spoilage as well as the development of foodborne illness. Thus, the influence of pathogen contamination on beef microbiota should be analyzed to evaluate food safety. We analyzed the influence of pathogen contamination on the shift in microbiota and the interactions between the pathogen and indigenous microbes in beef stored under different conditions. Sixty beef samples were stored at 25 °C and 4 °C for 24 h, and the shifts in microbiota were analyzed using the MiSeq system. The influence of pathogen contamination on microbiota was analyzed by artificial contamination experiments with Escherichia coli FORC_044, which was isolated from the stool of a food poisoning patient in Korea. The bacterial amounts and the proportion of Escherichia were higher when the beef was stored at 25 °C. Artificially contaminated Escherichia positively correlated with the indigenous microbes such as Pseudomonas, Brochothrix, Staphylococcus, Rahnella, and Rhizobium as determined by co-occurrence network analyses. Carnobacterium, a potential spoilage microbe, was negatively correlated with other microbes. The predicted functions of altered microbiota showed that the pathways related to the process of spoilage including biosynthesis of acetic acid and lactic acid increased over time. The shift in pathways was more pronounced in contaminated beef stored at 25 °C. Carnobacterium, Lactobacillus, and Escherichia were the main genera contributing to the shift in the relative abundance of functional genes involved in the various spoilage pathways. Our results indicated that pathogen contamination could influence beef microbiota and mediate spoilage. This study extends our understanding of the beef microbiota and provides insights into the role of pathogen and storage conditions in meat spoilage.
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http://dx.doi.org/10.1016/j.foodres.2020.109118DOI Listing
June 2020

Risk factors for mortality in patients with pulmonary mucormycosis.

Mycoses 2020 Jul 6;63(7):729-736. Epub 2020 May 6.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: Pulmonary mucormycosis (PM) represents a serious burden in terms of morbidity and mortality in immunocompromised patients. Studies of prognostic factors in patients with PM are limited and have involved small numbers of patients.

Methods: Adult patients diagnosed with proven and probable PM according to the modified definitions of the EORTC/MSG 2008 in a tertiary hospital in Seoul, South Korea, between 2008 and 2019 were retrospectively enrolled.

Results: A total of 49 patients including 31 (63%) with proven PM and 18 (37%) with probable PM were enrolled. The 90-day mortality rate was 49% (24/49). Neutropenia, thrombocytopenia, use of voriconazole at clinical suspicion, positivity of non-sterile culture, use of steroid and treatment without surgery were more common in fatal cases than non-fatal cases. Voriconazole use at clinical suspicion for invasive mould pneumonia (OR 6.91, P = .01) and prolonged neutropenia (OR 4.86, P = .03) were independent risk factors for mortality. Voriconazole use at clinical suspicion was associated with positive galactomannan (GM) assay (OR 5.93, P = .02) and history of invasive pulmonary aspergillosis (OR, 6.88, P = .05).

Conclusion: About half of the patients with PM died within 90 days of diagnosis, and fatal outcomes were common in patients with prolonged neutropenia and empirical voriconazole use. Caution is needed in using voriconazole even in patients with positive GM results and prior histories of invasive pulmonary aspergillosis in whom PM cannot be ruled out by differential diagnosis.
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http://dx.doi.org/10.1111/myc.13092DOI Listing
July 2020

The transcriptional regulator IscR integrates host-derived nitrosative stress and iron starvation in activation of the operon in .

J Biol Chem 2020 04 13;295(16):5350-5361. Epub 2020 Mar 13.

National Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, and Center for Food Safety and Toxicology, Seoul National University, Seoul 08826, South Korea

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen produces a cytolysin/hemolysin protein encoded by the operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the promoter P , which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates transcription by directly binding upstream of P , whereas the histone-like nucleoid-structuring protein (H-NS) represses by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the P regulatory region, resulting in the release of H-NS repression and induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of P provides with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of transcription, thereby enabling successful host infection.
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http://dx.doi.org/10.1074/jbc.RA120.012724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170529PMC
April 2020

Real-Time Measurement of the Liquid Amount in Cryo-Electron Microscopy Grids Using Laser Diffraction of Regular 2-D Holes of the Grids.

Mol Cells 2020 Mar;43(3):298-303

Department of Agricultural Biotechnology, Center for Food Safety and Toxicology, Center for Food and Bioconvergence, and Research Institute for Agriculture and Life Sciences, CALS, Seoul National University, Seoul 08826, Korea.

Cryo-electron microscopy (cryo-EM) is now the first choice to determine the high-resolution structures of huge protein complexes. Grids with two-dimensional arrays of holes covered with a carbon film are typically used in cryo-EM. Although semi-automatic plungers are available, notable trial-and-error is still required to obtain a suitable grid specimen. Herein, we introduce a new method to obtain thin ice specimens using real-time measurement of the liquid amounts in cryo-EM grids. The grids for cryo-EM strongly diffracted laser light, and the diffraction intensity of each spot was measurable in real-time. The measured diffraction patterns represented the states of the liquid in the holes due to the curvature of the liquid around them. Using the diffraction patterns, the optimal time point for freezing the grids for cryo-EM was obtained in real-time. This development will help researchers rapidly determine highresolution protein structures using the limited resource of cryo-EM instrument access.
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http://dx.doi.org/10.14348/molcells.2020.2238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103880PMC
March 2020