• Journal of Microbiology and Biotechnology
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• v.27 no.4
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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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• v.29 no.11
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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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• v.16 no.2
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• pp.172-181
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• 2009

Purpose: To identify trends in causative bacterial organisms for neonatal sepsis and antimicrobial susceptibilities over 10 years in one neonatal intensive care unit. Methods: We retrospectively reviewed the cases of culture-proven neonatal sepsis between January 1998 and December 2007. The 10-year period was divided into two phases (phase I, 1998-2002; phase II, 2003-2007) to distinguish the differences during the entire period. Results: Total 350 episodes of neonatal sepsis were identified in 315 neonates. The common pathogens of early-onset sepsis were S. epidermidis, S. aureus, P. aeruginosa, and E. cloacae in phase I, and S. epidermidis and E. cloacae in phase II. In cases of late-onset sepsis, coagulase negative Staphylococcus, S. aureus, and K. pneumoniae were isolated frequently in both phases. The incidence of sepsis caused by multi-drug resistant organisms decreased with strict infection control. Gram positive organisms showed 0-20% susceptibility to penicillin, ampicillin, and cefotaxime in both phases. Sensitivity to amikacin for Enterobacter spp. increased, whereas P. aeruginosa showed decreased sensitivity in phase II. Between 50% and 60% of other gram negative bacteria, except P. aeruginosa, were susceptible to cefotaxime in phase II in contrast to phase I. Greater than 80% of gram negative bacteria were sensitive to imipenem except P. aeruginosa and ciprofloxacin in both phases. Conclusion: The trend in causative microorganisms and antimicrobial susceptibilities can be used as a guideline for selection of appropriate antibiotics. A particular attention should be paid to infection control, especially to reduce sepsis caused by multi-drug resistant organisms.

• Journal of Microbiology and Biotechnology
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• v.25 no.10
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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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• v.33 no.6
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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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• v.28 no.3
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• pp.149-159
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• 2021

Purpose: Antibiotic exposure during pregnancy may affect the fetus and newborn in many ways. This study investigated the impact of prenatal antibiotic exposure duration on neonatal outcomes in very preterm (VP) or very low birth weight (VLBW) infants. Methods: From September 2015 to December 2020, preterm infants with gestational age less than 32 weeks or with a BW less than 1,500 g who were admitted to the neonatal intensive care unit, and their mothers were enrolled. Prenatal antibiotic exposure was defined as antibiotics received by mothers before delivery, and the patients were categorized into the non-antibiotic group, short-duration (SD; ≤7 days) group, or long-duration (LD; >7 days) groups. Results: A total of 93 of 145 infants were exposed to prenatal antibiotics, among which 35 (37.6%) were in the SD group and 58 (62.4%) were in the LD group. Infants in the LD group had a significantly higher birth weight-for-gestational-age (BW/GA) Z-score than those in the non-antibiotic group, even after the adjustment for confounding factors (beta, 0.258; standard error, 0.149; P<0.001). Multivariate logistic regression analysis showed that prolonged prenatal antibiotic exposure was independently associated with death (adjusted odds ratio [aOR], 8.926; 95% confidence interval [CI], 1.482-53.775) and composite outcomes of death, necrotizing enterocolitis (NEC), and late-onset sepsis (LOS) (aOR, 2.375; 95% CI, 1.027-5.492). Conclusions: Prolonged prenatal antibiotic exposure could increase the BW/GA Z-score and the risk of death and composite outcomes of death, NEC, and LOS in VP or VLBW infants.