• Title/Summary/Keyword: anti-bacterial agents

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Antimicrobial resistance in Klebsiella pneumoniae: identification of bacterial DNA adenine methyltransferase as a novel drug target from hypothetical proteins using subtractive genomics

  • Umairah Natasya Mohd Omeershffudin;Suresh Kumar
    • Genomics & Informatics
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    • v.20 no.4
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    • pp.47.1-47.13
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    • 2022
  • Klebsiella pneumoniae is a gram-negative bacterium that is known for causing infection in nosocomial settings. As reported by the World Health Organization, carbapenem-resistant Enterobacteriaceae, a category that includes K. pneumoniae, are classified as an urgent threat, and the greatest concern is that these bacterial pathogens may acquire genetic traits that make them resistant towards antibiotics. The last class of antibiotics, carbapenems, are not able to combat these bacterial pathogens, allowing them to clonally expand antibiotic-resistant strains. Most antibiotics target essential pathways of bacterial cells; however, these targets are no longer susceptible to antibiotics. Hence, in our study, we focused on a hypothetical protein in K. pneumoniae that contains a DNA methylation protein domain, suggesting a new potential site as a drug target. DNA methylation regulates the attenuation of bacterial virulence. We integrated computational-aided drug design by using a bioinformatics approach to perform subtractive genomics, virtual screening, and fingerprint similarity search. We identified a new potential drug, koenimbine, which could be a novel antibiotic.

A Review of Studies on Antibiotic Course and Antibiotic Resistance in Nasopharyngeal Pathogens in Primary Care Setting (일차진료 항생제 치료기간과 비인두 항생제 내성률에 대한 연구 고찰)

  • Shin, Hyang Hwa;Lee, Sun Haeng;Yun, Sung Joong;Chang, Gyu Tae
    • The Journal of Pediatrics of Korean Medicine
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    • v.32 no.2
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    • pp.64-71
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    • 2018
  • Objectives The purpose of this study is to examine the correlation of antibiotics administration duration and antimicrobial resistance by reviewing domestic and foreign literatures. Methods We searched literatures dated up to 23 February, 2018 in PubMed and Cochrane Library using terms of "Anti-Bacterial Agents", "Carrier State", "Nasopharynx", "Drug Administration Schedule", and also searched via RISS (Research Information Service System), KISS (Koreanstudies Information Service System), DBpia (DataBase Periodical Information Academic) using terms of antibiotics, resistance, and dose. Results In comparison with shortened and standard antibiotic course, longer treatment duration is associated with greater antimicrobial resistance or non-significant difference, but we cannot find literature that shortened antibiotic course increases antimicrobial resistance on human nasopharyngeal flora. Conclusions Currently, there is no evidence that completing the standard antibiotic course reduces antimicrobial resistance. It can be a strategy for reducing antibiotic use to apply Korean medicine treatment, as well as short-course antibiotic therapy or delayed antibiotic prescription. Additional well-designed trials should be conducted in domestic and foreign settings about the appropriate duration of antibiotic therapy.

High Efficiency Binding Aptamers for a Wide Range of Bacterial Sepsis Agents

  • Graziani, Ana Claudia;Stets, Maria Isabel;Lopes, Ana Luisa Kalb;Schluga, Pedro Henrique Caires;Marton, Soledad;Ferreira, Ieda Mendes;de Andrade, Antero Silva Ribeiro;Krieger, Marco Aurelio;Cardoso, Josiane
    • 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.

Effects of C-Terminal Residues of 12-Mer Peptides on Antibacterial Efficacy and Mechanism

  • Son, Kkabi;Kim, Jieun;Jang, Mihee;Chauhan, Anil Kumar;Kim, Yangmee
    • 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 12th 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.

A Study on the Functionality in Natural Colorants

  • Song, Eun-Young;Ahn, In-Yong;Suh, Hwa-Jin;Kim, Mi-Jin;Park, Jin-Woo;Kwon, Oh-Oun
    • Proceedings of the Korean Society of Dyers and Finishers Conference
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    • 2012.03a
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    • pp.122-122
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    • 2012
  • The aims of this study were to examine the efficacy of phytochemical compounds of colorants as anti-oxidant agent. The bioactive properties of natural colorants were studied by total phenolic contents, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and anti-bacterial activity in Escherichial coli. The concentration ($IC_{50}$) of various extracts from colorants required to exert 50% reducing effect on DPPH radical were found to be 0.007-4 mg/ml. Especially, the gallnut (Schlectendalia Chinensis) displayed remarkable effect of DPPH as compared to positive control ascorbic acid. The total phenolic contents (TPC) and restraint of E coli. also analyzed. It was found that gallnut extracts effectively inhibited DPPH radical at a concentration below 0.01 mg/ml. Natural colorant extracts could be of good resources as anti-oxidant and anti-bacterial agents. The results suggest that our study may contribute to the development of natural and functional materials with potential application to reduce oxidative damage.

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Anti-Endotoxin 9-Meric Peptide with Therapeutic Potential for the Treatment of Endotoxemia

  • Krishnan, Manigandan;Choi, Joonhyeok;Choi, Sungjae;Kim, Yangmee
    • Journal of Microbiology and Biotechnology
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    • v.31 no.1
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    • pp.25-32
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    • 2021
  • Inflammatory reactions activated by lipopolysaccharide (LPS) of gram-negative bacteria can lead to severe septic shock. With the recent emergence of multidrug-resistant gram-negative bacteria and a lack of efficient ways to treat resulting infections, there is a need to develop novel anti-endotoxin agents. Antimicrobial peptides have been noticed as potential therapeutic molecules for bacterial infection and as candidates for new antibiotic drugs. We previously designed the 9-meric antimicrobial peptide Pro9-3 and it showed high antimicrobial activity against gram-negative bacteria. Here, to further examine its potency as an anti-endotoxin agent, we examined the anti-endotoxin activities of Pro9-3 and elucidated its mechanism of action. We performed a dye-leakage experiment and BODIPY-TR cadaverine and limulus amebocyte lysate assays for Pro9-3 as well as its lysine-substituted analogue and their enantiomers. The results confirmed that Pro9-3 targets the bacterial membrane and the arginine residues play key roles in its antimicrobial activity. Pro9-3 showed excellent LPS-neutralizing activity and LPS-binding properties, which were superior to those of other peptides. Saturation transfer difference-nuclear magnetic resonance experiments to explore the interaction between LPS and Pro9-3 revealed that Trp3 and Tlr7 in Pro9-3 are critical for attracting Pro9-3 to the LPS in the gram-negative bacterial membrane. Moreover, the anti-septic effect of Pro9-3 in vivo was investigated using an LPS-induced endotoxemia mouse model, demonstrating its dual activities: antibacterial activity against gram-negative bacteria and immunosuppressive effect preventing LPS-induced endotoxemia. Collectively, these results confirmed the therapeutic potential of Pro9-3 against infection of gram-negative bacteria.

Screening of New Antibiotics Inhibiting Bacterial Methionyl-tRNA Synthetase (세균의 Methionyl-tRNA Synthetase를 저해하는 새로운 항생물질의 스크리닝)

  • 곽진환;조영준;송난규
    • YAKHAK HOEJI
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    • v.45 no.3
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    • pp.245-250
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    • 2001
  • Aminoacyl tRNA synthetases of bacteria are known as potential targets for new anti-microbial agents. To isolate new inhibitors of bacterial methionyl-tRNA synthetases from natural sources, a new target-oriented screening system using whole cells which are over-expressing a target enzyme was developed. Approximately 8,000 culture broths of microorganisms from soils were tested by this screening system. Among them, ten culture broths was found to contain inhibitory activity against methionyl -tRNA synthetases of Escherichia coli. For the validation of the screening system, this new method was compared with in vitro enzymatic method. Seven out of 10 culture broths showed inhibitory activity against methionyl-tRNA synthetases of E. coli. This result showed that the new screening system was comparable to the enzyme assay. Thus we believe that our screening system as a new method can be applied for the screening of new antibiotics inhibiting bacterial methionyl-tRNA synthetases from natural products.

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Formulation of Liquid Coating Agent using Bamboo Charcoal and its Characteristics (대나무숯 액상코팅제의 제조 및 특성)

  • Park, Sang-Bum;Lee, Hee-Young;Lee, Sang-Min;Park, Jong-Young
    • Journal of the Korean Wood Science and Technology
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    • v.36 no.6
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    • pp.113-120
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    • 2008
  • This study was performed to develop environmentally-friendly finishing materials for construction. In order to abate formaldehyde and ammonia in indoor air, liquid coating agents for indoor finishing were formulated with bamboo charcoal powder, cypress extracted water, and water-borne acrylic binder. Deodorization rate, far-infrared ray emission rate, anions emission amount, and anti-bacterial effect were investigated. Deodorization rate was increased as cypress extracted water content increased. Deodorization rates of the coating agents were 60.0~98.6% on formaldehyde and 76.7~86.2% on ammonia. No differences on far-infrared ray emission rate, anions emission amount, and anti-bacterial effect were found depending on different formulations. A 91.7% of far-infrared ray emission rate, 77 ea/cc of anions emission amount, and 99.4% of anti-bacterial effect were detected for all formulations. More effective application method of the coating agents revealed was a spray-gun. A $0.66kg/m^2$ of coating agent with a spray-gun and $0.94kg/m^2$ of coating agent with a brush was consumed each.

Clostridium difficile in Children: To Treat or Not to Treat?

  • Shim, Jung Ok
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.17 no.2
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    • pp.80-84
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    • 2014
  • Clostridium difficile infection has been increasing since 2000 in children and in adults. Frequent antibiotics use, comorbidity, and the development of hypervirulent strains have increased the risk of infection. Despite the high carriage rates of C. difficile, infants rarely develop clinical infection. Discontinuing antibiotics and supportive management usually leads to resolution of disease. Antibiotics use should be stratified depending on the patient's age and severity of the disease.

The Anti-inflammatory Effect of Green Tea Extract Against Prevotella intermedia (녹차추출물의 잇몸 질환 원인균에 대한 항염증 효능 연구)

  • Min, Dae-Jin;Yi, Sung-Won;Lee, Sung-Hoon;Kim, Seung-Seob;Kim, Chan-Ho;Lee, John-Hwan;Bae, Ji-Hyun;Kim, Han-Kon
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.37 no.1
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    • pp.67-73
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    • 2011
  • Dental bacteria can cause gum diseases, i.e. gingivitis and periodontitis, by inducing inflammation in human gingiva. Therefore, the most effective way to prevent and treat gum diseases is the control of the inflammatory reactions induced by dental bacteria. Almost all present dental care products contain anti-bacterial agents to eliminate dental bacteria. However, recent studies report that even heat-killed dental bacteria can induce the inflammation responses in oral cells. Therefore, the method using anti-bacterial agents should be improved for better anti-inflammatory effect and the effective natural anti-inflammatory substances need to be found. In addition, the mechanisms of gingival inflammation should be elucidated. In this study, we tried to find out the mechanism of the gingival inflammation and effective natural anti-inflammatory substances with human gingival epithelial cells and Prevotella intermedia which is well known as a typical dental bacteria inducing gingivitis and periodontitis. In results, Prevotell intermedia initiated the gingival inflammation response by stimulating gingival epithelial cells to release an inflammatory cytokine, IL-8. Furthermore, the inflammation by Prevotella intermedia is related to COX-2, AP-1, and TNF-${\alpha}$ pathways. Green tea extract could effectively suppress the inflammatory responses induced by Prevotella intermedia. We find out the effective natural substance for the improvement of gum diseases by studying the mechanism of the gingival inflammation induced by dental bacteria.