• Journal of Microbiology and Biotechnology
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• 제29권12호
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• pp.1931-1937
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• 2019

The heterologous expression of the Streptomyces natural product (NP) biosynthetic gene cluster (BGC) has become an attractive strategy for the activation, titer improvement, and refactoring of valuable and cryptic NP BGCs. Previously, a Streptomyces artificial chromosomal vector system, pSBAC, was applied successfully to the precise cloning of large-sized polyketide BGCs, including immunosuppressant tautomycetin and antibiotic pikromycin, which led to stable and comparable production in several heterologous hosts. To further validate the pSBAC system as a generally applicable heterologous expression system, the daptomycin BGC of S. roseosporus was cloned and expressed heterologously in a model Streptomyces cell factory. A 65-kb daptomycin BGC, which belongs to a non-ribosomal polypeptide synthetase (NRPS) family, was cloned precisely into the pSBAC which resulted in 28.9 mg/l of daptomycin and its derivatives in S. coelicolor M511(a daptomycin non-producing heterologous host). These results suggest that a pSBAC-driven heterologous expression strategy is an ideal approach for producing low and inconsistent Streptomyces NRPS-family NPs, such as daptomycin, which are produced low and inconsistent in native host.

• Pediatric Infection and Vaccine
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• 제29권2호
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• pp.105-109
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• 2022

다제내성 반코마이신 저항성 장내구균(multidrug-resistant vancomycin-resistant enterococci, VRE)에 의한 침습감염의 치료는 특히 기저질환을 가진 소아 환자들에게 어려운 점이 있다. 소아환자들에게서 VRE 감염을 치료하기 위한 새로운 항생제에 대한 연구가 충분히 이루어지지 않았다. 본 증례는 심폐이식을 받은 생후 6개월 된 영아에서 linezolid 중단 이후 재발된 VRE 균혈증에 대해 daptomycin과 tigecycline 조합으로 성공적으로 치료하여 이를 보고하는 바이다.

• Journal of Microbiology and Biotechnology
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• 제16권12호
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• pp.1841-1848
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• 2006

Insights into gene expression have the potential for improvement of antibiotic yield and the development of robust production hosts for use in recombinant biomolecule production. $Cubicin^{TM}$ (daptomycin for injection) is a recently approved antibiotic active against many Gram(+) pathogens, including those resistant to methicillin, vancomycin, and fluoroquinolones. Daptomycin is produced as a secondary metabolite by Streptomyces roseosporus. A 128 kb region of DNA including the daptomycin biosynthetic gene cluster (dpt) has been cloned. and sequenced. Using a selected array of nucleic acid probes representing this region, we compared the expression levels of the dpt genes between S. roseosporus wild-type (WT) and derived S. roseosporus high-producer of daptomycin (HP). We observed that the majority of the biosynthetic genes were upregulated in HP compared with WT; a total of 12 genes, including those encoding daptomycin synthetase, showed consistently and significantly higher expression levels, at least 5-fold, in HP compared with WT. In contrast, some genes, flanking the dpt cluster, were expressed at higher levels in the WT strain. The expression of housekeeping genes such as S. roseosporus rpsL, rpsG, and 16S (positive controls) and presumptive intergenic regions in the dpt cluster (negative control) were identical in the two strains. In addition, we compared transcription during the early, mid-log, and early-stationary phases of growth in the HP strain. The same set of genes was upregulated and downregulated under all conditions examined; housekeeping genes showed no relative change in expression level over the periods of growth tested. Analyses of this type would be of value in studies of strain improvement and also for the identification of gene regulation processes that are important for secondary metabolite production.

• BMB Reports
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• 제40권6호
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• pp.881-887
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• 2007

It is a hot clinical issue whether newly approved antimicrobial agents such as daptomycin, linezolid, quinupristin/dalfopristin (synercid) and tigecycline are active enough to be used for infections caused by vancomycin resistant bacteria. We performed susceptibility tests for mupirocin, which is in widespread clinical use in Korea, and four new antimicrobials, daptomycin, linezolid, quinupristin/dalfopristin and tigecycline, against vancomycin-resistant Enterococcus faecalis and Enterococcus faecium isolated from Korean patients in 1998 and 2005 to evaluate and compare the in vitro activity of these antimicrobials. Among these agents, quinupristin/dalfopristin, which is rarely used in hospitals in Korea, showed relatively high resistance to several vancomycin-resistant enterococci (VRE) isolated in 2005. Likewise, daptomycin, linezolid and tigecycline have not yet been in clinical use in Korea. However, our results showed that most of the 2005 VRE isolates were already resistant to linezolid and daptomycin (highest minimum inhibitory concentration (MIC) value >$100{\mu}g$/ml). Compared with the other four antimicrobial agents tested in this study, tigecycline generally showed the greatest activity against VRE. However, four strains of 2005 isolates exhibited resistance against tigecycline (MIC >$12.5{\mu}g$/ml). Almost all VRE were resistant to mupirocin, whereas all E. faecium isolated in 1998 were inhibited at concentrations between $0.8\sim1.6{\mu}g$/ml. In conclusion, resistances to these new antimicrobial agents were exhibited in most of VRE strains even though these new antibiotics have been rarely used in Korean hospitals.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2008년도 International Meeting of the Microbiological Society of Korea
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• pp.169-169
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• 2008

• 약학회지
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• 제53권4호
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• pp.194-200
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• 2009

Community-acquired antimicrobial resistant bacteria are an emerging problem whole world-wide. Generally, Hands are main mediator of pathogen transmission as compared with other body parts. So, the purpose of this research was to investigate the microbiological quality and antimicrobial susceptibilities of samples which were collected from the door knob and surface in public- and home-facilities, and also hand. Of total 191 samples, 71 samples (37%) were shown to be of high-level total bacterial count (>$10^8\;CFU/cm^2$). And presence of Staphylococcus and Enteric bacilli was observed in 61 samples (32%) and 76 samples (40%), respectively. Antimicrobial susceptibilities of staphylococcal isolates from the samples were tested for six different antimicrobial agents, which are in wide spread clinical use in Korea, as well as four new antimicrobials, daptomycin, linezolid, quinupristin/dalfopristin and tigecycline. Among staphylococcal isolates, antimicrobial resistance were observed in oxacillin (n=6), mupirocin (n=7), vancomycin (n=1), quinupristin/dalfopristin (n=2) and gentamicin (n=5). Fortunately, all the isolates were susceptible to new antimicrobial such as daptomycin, linezolid and tigecycline. Furthermore 4 Enterococcus faecalis were isolated from four hand samples, and all these isolates exhibited multidrug resistance to four different antimicrobial (oxacillin, quinupristin/dalfopristin, mupirocin, gentamicin). Also, 5 Escherichia coli were isolated from surface in home (n=3), door knob in public facilities (n=1) and hand (n=1). Escherichia coli isolated from hand was high-level resistant to tigecycline ($128{\mu}g$/ml) and gentamicin ($64{\mu}g$/ml).

• Pediatric Infection and Vaccine
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• 제16권1호
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• pp.1-5
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• 2009

Methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of nosocomial infections, has been increasingly recognized in communities of the United States. This article will review the clinical spectrum and treatment of MRSA infections in children in the context of recent epidemiological changes of MRSA infections. In general, community-associated (CA) MRSA most frequently causes skin and soft tissue infections and has an increased association with invasive infections, particularly pneumonia and musculoskeletal infections. Hospital-associated (HA) MRSA strains tend to be associated with bloodstream infections, pneumonia, and surgical site infections. Different from the United States, CA-MRSA infections are not common in Korea (only 5.9%); however, there are some CA-MRSA clones that are different from HA-MRSA clones in Korea and from CA-MRSA clones in other countries. The treatment of MRSA infections should be guided by antimicrobial susceptibility testing, the site of infection, and the infection severity. Vancomycin is the treatment of choice for invasive MRSA infections. Other agents such as trimethoprim-sulfamethoxazole, clindamycin, linezolid, quinupristin-dalfopristin, and daptomycin have been used for some conditions.

• Pediatric Infection and Vaccine
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• 제16권1호
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• pp.6-12
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• 2009

There are relatively few novel antimicrobial agents despite the dramatic increase in antimicrobial resistance and multiple drug resistance of clinical isolates worldwide. Vancomycin is still the most widely used antibiotic for treating resistant Gram-positive coccal infections in children, especially for methicillin-resistant Staphylococcus aureus. For children with Gram-positive coccal infections where vancomycin is not effective or older therapeutic agents cannot be tolerated, linezolid, quinupristin-dalfopristin or daptomycin may be useful in the appropriate clinical setting. For Gram-negative bacterial infections, new carbapenems await clinical application. Tebipenem pivoxil is a novel oral carbapenem undergoing clinical trials for acute otitis media in pediatric patients. Antiviral drug development is now progressing at the pace of antibiotic development 30 years ago. Newer antiviral agents used for the treatment of herpes viruses and hepatitis C virus infections in children are included in this review.

• Environmental Analysis Health and Toxicology
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• 제22권4호
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• pp.313-320
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• 2007

본 연구는 인간의 건강과 식품의 오염을 예방하기 위한 유용한 자료를 얻기 위하여 육류(소고기, 닭고기, 돼지고기)로부터 분리된 staphylococci를 가지고 한국에서 광범위하게 사용되는 6가지 항생제와 daptomycin, linezolid, quinupristin/dalfopristin and tigecycline과 같은 4가지의 신항생제에 대한 항생제 감수성 시험을 수행하였다. 이에 더하여 육류의 세균 오염실태를 조사하기 위하여 총 세균수와 대장균수를 측정하였다. 그 결과 147개의 육류 샘플 중 48%의 샘플에서 일반세균수의 기준에 부적합한 결과가 나타났으며, 대장균수에 대해서는 31%의 샘플에서 기준에 부적합한 결과가 나타났다. 또한 육류의 91%에서 stapylococci가 검출되었으며 이들 staphylococci는 Coagulase Negative Staphylococci (CNS)와 S. aureus로 동정되었다. 분리된 staphylococci의 5.4%가 methicillin (oxacillin)에 내성을 나타내었고, 특히 mupirocin ($MIC_{90},\;>\;12\;{\mu}g/mL$) gentamicin ($MIC_{90},\;64\;{\mu}g/mL$)에 높은 내성을 나타내었다. 그러나 신항생제에 대해서는 methicillin 내성 staphylococci를 포함한 모든 staphylococci 분리균주가 높은 감수성을 나타내었다. 결론적으로 본 연구의 결과들은 육류가 소비자들의 건강에 중요한 위험요소로 작용할 수 있음을 보여주고 있다.

• 약학회지
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• 제52권6호
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• pp.434-440
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• 2008

The purpose of this research was to investigate the microbiological quality and antimicrobial susceptibilities of the ready-to-eat side dishes, which are were collected from the grocery stores, big markets, and department stores in Seoul throughout November, 2007. Of total 124 samples, presence of staphylococci and enteric bacilli was observed in 38 samples (31%) and 53 samples (43%), respectively. And 30 samples (24%) were shown to be of unsatisfactory quality for total bacterial count (>$10^5$). Antimicrobial susceptibilities of the staphylococci isolated from the side dishes were tested for six different antimicrobial agents, which are in widespread clinical use in Korea, as well as four new antimicrobials, daptomycin, linezolid, quinupristin/dalfopristin and tigecycline. As a result, the staphylococcal isolates were found to be resistant to oxacillin (${MIC}_{90}$, >128 ${\mu}g$/ml), teicoplanin (${MIC}_{90}$, >128 ${\mu}g$/ml), mupirocin (${MIC}_{90}$, >128 ${\mu}g$/ml), linezolid (${MIC}_{90}$, 128 ${\mu}g$/ ml) and quinupristin/dalfopristin (${MIC}_{90}$, 32 ${\mu}g$/ml). Especially, some of the staphylococcal isolates exhibited high level and multi-drug resistance. Moreover, these bacteria were also resistant to new antimicrobials, except tigecycline.