• Journal of Microbiology and Biotechnology
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• 제27권4호
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• pp.838-843
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• 2017

Sepsis is a major health problem worldwide, with an extremely high rate of morbidity and mortality, partly due to delayed diagnosis during early disease. Currently, sepsis diagnosis requires bacterial culturing of blood samples over several days, whereas PCR-based molecular diagnosis methods are faster but lack sensitivity. The use of biosensors containing nucleic acid aptamers that bind targets with high affinity and specificity could accelerate sepsis diagnosis. Previously, we used the systematic evolution of ligands by exponential enrichment technique to develop the aptamers Antibac1 and Antibac2, targeting the ubiquitous bacterial peptidoglycan. Here, we show that these aptamers bind to four gram-positive and seven gram-negative bacterial sepsis agents with high binding efficiency. Thus, these aptamers could be used in combination as biological recognition elements in the development of biosensors that are an alternative to rapid bacteria detection, since they could provide culture and amplification-free tests for rapid clinical sepsis diagnosis.

• Journal of Microbiology and Biotechnology
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• 제29권11호
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• pp.1707-1716
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• 2019

The development of new antimicrobial agents is essential for the effective treatment of diseases such as sepsis. We previously developed a new short peptide, Pap12-6, using the 12 N-terminal residues of papiliocin, which showed potent and effective antimicrobial activity against multidrug-resistant Gram-negative bacteria. Here, we investigated the antimicrobial mechanism of Pap12-6 and a newly designed peptide, Pap12-7, in which the 12^th Trp residue of Pap12-6 was replaced with Val to develop a potent peptide with high bacterial selectivity and a different antibacterial mechanism. Both peptides showed high antimicrobial activity against Gram-negative bacteria, including multidrug-resistant Gram-negative bacteria. In addition, the two peptides showed similar anti-inflammatory activity against lipopolysaccharide-stimulated RAW 264.7 cells, but Pap12-7 showed very low toxicities against sheep red blood cells and mammalian cells compared to that showed by Pap12-6. A calcein dye leakage assay, membrane depolarization, and confocal microscopy observations revealed that the two peptides with one single amino acid change have different mechanisms of antibacterial action: Pap12-6 directly targets the bacterial cell membrane, whereas Pap12-7 appears to penetrate the bacterial cell membrane and exert its activities in the cell. The therapeutic efficacy of Pap12-7 was further examined in a mouse model of sepsis, which increased the survival rate of septic mice. For the first time, we showed that both peptides showed anti-septic activity by reducing the infiltration of neutrophils and the production of inflammatory factors. Overall, these results indicate Pap12-7 as a novel non-toxic peptide with potent antibacterial and anti-septic activities via penetrating the cell membrane.

• Neonatal Medicine
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• 제16권2호
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• pp.172-181
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• 2009

목 적 : 신생아 사망 및 이환의주요 원인인 패혈증의 치료에 있어서 적절한 항생제의 선택은 항생제 내성을 줄이고 다약제 내성 균주의 출현을 방지할 수 있다. 이제 저자들은 단일 신생아중환자실에서 경험한 신생아 패혈증 빈도와 원인균 및 항생제 감수성 변화를 지난 10년간에 걸쳐 조사하였다. 방 법 : 1998년 1월부터 2007년 12월까지 본원 신생아 중환자실에 입원한 환아 중 혈액 배양 검사상 균이 동정되었던 환아들을 대상으로 의무기록을 통해 1998년부터 2002년까지를 전반기, 2003년부터 2007년까지를 후반기로 구분하여 각 발생 시기에 따른 패혈증의 원인균과 항생제 감수성을 후향적으로 분석하였다. 결 과 : 315명의 환아가 총 350례의 패혈증을 경험하였으며, 조기 패혈증의 원인균으로는 전반기는 S. epidermidis, S.aureus, P. aeruginosa, Enterobacter cloacae, 후반기에는 S. epidermidis, E. cloacae가 흔하게 검출되었다. 후기 패혈증의 경우는 전반기에는 coagulase negative S. epidermidis, S. aureus, K. pneumoniae가 전반기와 후반기 모두에서 가장 흔하게 배양되었다. 다약제 내성균에 의한 패혈증은 엄격한 감염관리를 시행한 이후 감소하는 경향을 보였다. 그람 양성균의 경우 penicillin, ampicillin, 그리고 cefotaxime에 대해 전후반기 모두에서 0-20%의 낮은 감수성을 보였다. 그람 음성균의 경우는 Enterobacter spp의 amikacin에 대한 감수성이 전반기(15.8%)에 비해 후반기(37.5%)에 증가하는 양상이었다. P. aeruginosa는 amikacin에 대해 전반기 33.3%에서 후반기 20%로 감수성이 감소하였다. P. aeruginosa를 제외한 그람 음성균은 cefotaxime에 대해 50-60% 정도의 항생제 감수성을 보였다. P. aeruginosa를 제외한 그람 음성균의 경우 imipenem과 ciprofloxacin에 대해 80% 이상의 감수성을 보였다. 결 론 : 지난 10년간의 신생아 패혈증의 원인균과 항생제 감수성의 변화양상을 확인하였으며, 이는 경험적 항생제 사용을 선택하는데 도움이 될 것으로 생각된다. 전반기에 비해 후반기에는 엄격한 감염관리를 통해 다약제 내성균에 의한 패혈증 및 전체 신생아 패혈증의 발생이 현저히 감소하였다. 따라서 신생아 패혈증의 발생과 감염에 의한 사망을 줄이기 위해서는 적절한 항생제 선택과 더불어 지속적인 감염관리가 필요할 것으로 사료된다.

• Journal of Microbiology and Biotechnology
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• 제25권10호
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• pp.1751-1760
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• 2015

Mucin2 (MUC2), an important regulatory factor in the immune system, plays an important role in the host defense system against bacterial translocation. Probiotics known to regulate MUC2 gene expression have been widely studied, but the interactions among probiotic, pathogens, and mucin gene are still not fully understood. The aim of this study was to investigate the role of MUC2 in blocking effects of probiotics on meningitic E. coli-induced pathogenicities. In this study, live combined probiotic tablets containing living Bifidobacterium, Lactobacillus bulgaricus, and Streptococcus thermophilus were used. MUC2 expression was knocked down in Caco-2 cells by RNA interference. 5-Aza-2'-deoxycytidine (5-Aza-CdR), which enhances mucin-promoted probiotic effects through inducing production of Sadenosyl-L-methionine (SAMe), was used to up-regulate MUC2 expression in Caco-2 cells. The adhesion to and invasion of meningitic E. coli were detected by competition assays. Our studies showed that probiotic agents could block E. coli-caused intestinal colonization, bacteremia, and meningitis in a neonatal sepsis and meningitis rat model. MUC2 gene expression in the neonatal rats given probiotic agents was obviously higher than that of the infected and uninfected control groups without probiotic treatment. The prohibitive effects of probiotic agents on MUC2-knockdown Caco-2 cells infected with E44 were significantly reduced compared with nontransfected Caco-2 cells. Moreover, the results also showed that 5-Aza-CdR, a drug enhancing the production of SAMe that is a protective agent of probiotics, was able to significantly suppress adhesion and invasion of E44 to Caco-2 cells by upregulation of MUC2 expression. Taken together, our data suggest that probiotic agents can efficiently block meningitic E. coli-induced pathogenicities in a manner dependent on MUC2.

• The Korean journal of internal medicine
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• 제33권6호
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• pp.1203-1209
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• 2018

Background/Aims: Adverse drug reaction (ADR) is an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product. The present study was conducted in order to monitor the frequency and severity of ADR during antimicrobial therapy of septicemia. Methods: A prospective, observational, and noncomparative study was conducted over a period of 6 months on patients of septicemia admitted at a university hospital. Naranjo algorithm scale was used for causality assessment. Severity assessment was done by Hartwig severity scale. Results: ADRs in selected hospitalized patients of septicemia was found to be in 26.5% of the study population. During the study period, 12 ADRs were confirmed occurring in 9, out of 34 admitted patients. Pediatric patients experienced maximum ADRs, 44.4%. Females experienced a significantly higher incidence of ADRs, 66.7%. According to Naranjo's probability scale, 8.3% of ADRs were found to be definite, 58.3% as probable, and 33.3% as possible. A higher proportion of these ADRs, 66.7% were preventable in nature. Severity assessment showed that more than half of ADRs were moderate. Teicoplanin was found to be the commonest antimicrobial agent associated with ADRs, followed by gemifloxacin and ofloxacin. Conclusions: The incidence and severity of ADRs observed in the present study was substantially high indicating the need of extra vigilant during the antimicrobial therapy of septicemia.

• Pediatric Infection and Vaccine
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• 제28권3호
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• pp.149-159
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• 2021

목적: 산모의 산전 항생제 사용은 여러가지 면에서 태아 및 신생아에 영향을 미칠 수 있다. 본 연구에서는 극소 미숙아 또는 극소 저체중출생아에서 산모의 산전 항생제 투여 기간이 신생아 예후에 미치는 영향에 대해 조사하였다. 방법: 2015년 9월부터 2020년 12월까지 고려대학교 안암병원에서 출생한 재태주수 32주 미만 또는 출생 체중 1,500 gram 미만인 신생아 및 산모를 대상으로 의무기록을 후향적으로 분석하였다. 산모의 산전 항생제 투여 기간에 따라 미투여 군, 7일 이하 군, 7일 초과 군의 세 군으로 나누어 산모의 특성, 환아의 특성 및 합병증 등을 비교 분석하였다. 결과: 총 145명 중 93명의 환아가 산전 항생제에 노출되었으며, 그 중 35명(37.6%)는 7일 이하 군, 58명(62.4%)는 7일 초과 군이었다. 7일 초과 군은 미투여 군에 비해 재태 연령에 따른 출생체중의 Z-score가 교란변수 보정 후에도 유의미하게 높았다(beta, 0.258; standard error, 0.149; P<0.001). 다변량 로지스틱 회귀 분석에서 7일 초과 군은 사망(adjusted odds ratio [aOR], 8.926; 95% confidence interval [CI], 1.482-53.775), 그리고 사망, 괴사성 장염, 후기 패혈증의 복합 평가 결과와 연관이 있었다(aOR, 2.375; 95% CI, 1.027-5.492). 결론: 산모의 장기간 산전 항생제 투여는, 극소 미숙아 또는 극소 저체중출생아에서 재태 연령에 따른 출생체중의 Z score을 증가시키며, 사망 뿐 아니라 사망, 괴사성 장염, 후기 패혈증의 복합 평가 결과의 위험도를 증가시킬 수 있다.