• 한국미생물·생명공학회지
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• 제43권4호
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• pp.396-400
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• 2015

Enterobacteriaceae에 속하는 세균들은 보건학적 문제를 발생시키기도 하며 항생제 내성 병원균의 발생으로 인하여 자연환경 중의 항생제 내성균에 분포에 대한 관심이 증대되고 있다. 따라서 배양법을 이용하여 국내 5개의 하천시료로부터 그람 음성 Enterobacteriaceae의 종 다양성을 조사하였으며 분리된 세균에 대한 다제내성을 항생제디스크 확산법으로 분석하였다. 그 결과, 분리된 그람 음성 Enterobacteriaceae는 Citrobacter, Enterobacter, Escherichia, Klebsiella, Kluyvera, Pantoea, Plesiomonas, Raoultella, Shigella로 동정되었으며 49%가 Enterobacter로서 우점종으로 분석되었다. 또한 이들 세균들의 78.3%가 조사된 13종의 항생제 중에서 7종 이상에 내성을 보였으며 이것은 국내 자연하천환경에 높은 비율의 다제내성균이 서식한다는 것을 제시한다.

• Genomics & Informatics
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• 제21권3호
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• pp.42.1-42.23
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• 2023

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

• 대한의생명과학회지
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• 제18권1호
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• pp.83-85
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• 2012

Vancomycin-resistant (VR)-E. faecium and VR-E. faecalis were isolated simultaneously from a rectal swab of a patient diagnosed with pneumonia in an intensive care unit (ICU). The patient was treated with various antibiotics including vancomycin. Only VR-E. faecium was continually isolated from the rectal swab at one and two weeks of the treatment. Identical vanA, IS1216V, and IS1542 genes were detected in both VR-E. faecium and VR-E. faecalis isolates which showed equal resistance against vancomycin and teicoplanin, but IS1251 was not detected. VR-E. faecium showed stronger multi-drug resistance than VE-E. faecalis. This result supports the reason why VR-E. faecium is one of the major pathogens in nosocomial infections.

• 생약학회지
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• 제28권3호
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• pp.162-165
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• 1997

Repeated column chromatographic works of hexane fraction of Aster scaber afforded some volatile mixtures of two or three components, which process potent inhibitory activity(more than 90% of control at $50{\mu}g/ml$) to the resistance of multi-drug resistant Staphylococcus aureus SA2 when combined with chlorampenicol($50{\mu}g/ml$).

• Archives of Plastic Surgery
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• 제34권6호
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• pp.691-696
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• 2007

Purpose: The emergency of multi-drug resistant stains of bacteria represents a challenge in the field of plastic surgery. Especially, MRSA(methycillin-resistant Staphylococcus aureus) and Pseudomonas aeruginosa have strong pathogenicity as well as multi-drug resistance so that they have become a lot more problematic strains. This study has been planned to reduce the bacterial burden by applying $Acticoat^{(R)}$(Smith & Nephew Healthcare, Hull, England)dressing into the chronic wounds infected by multi-drug resistant strains and to facilitate their healing. Methods: Nanocrystalline silver dressings($Acticoat^{(R)}$) were applied to chronic wound infected by MRSA or Pseudomonas aeruginosa. Multi-drug resistant bacteria were smeared over a slide glass using sterilized cotton swabs and gram stains were performed directly before and after applying $Acticoat^{(R)}$ dressings at 1, 24, 48 and 72 hours. The gram-stained slides were observed using an optical microscope magnified 1000 times(${\times}1000$). The bacterial counts of the control group(0 hour) were compared to those of the experimental groups(1, 24, 48, and 72 hour). Paired T-test was used to assess a statistical significance. MRSA was cultured in two BAPs(blood agar plate) and two MacConkey plates with streak plate method. None were interventions on one culture plate, while on the other culture plate, $Acticoat^{(R)}$ was placed in a square shape and cultured for 72 hours at $37^{\circ}C$, then plates were examined. Pseudomonas aeruginosa was cultured in the same manner as MRSA. Results: There are the large amount of declination of bacterial counts with statistical significance after $Acticoat^{(R)}$ dressing. The bacteria grew in culture plate without specific intervention, but no bacteria grew in culture plate with applying of $Acticoat^{(R)}$ dressing. Conclusion: We believe that $Acticoat^{(R)}$ dressing could be used as an effective method of treating chronic wounds which are infected by multi-drug resistant organisms.

• 생약학회지
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• 제39권4호
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• pp.369-380
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• 2008

The essential oils from 73 aromatic herb drugs entered on Korean official formularies were tested for antibioticresistance inhibitory effect. When the oils were combined with ampicillin (Am) or amoxicillin (Amx) they showed significant inhibitory effects on the growth of multi-drug resistant Staphylococcus aureus SA2 in considerably low concentration. The most effective combination were oils from Magnoliae Flos or Piperis longi Fructus ($25{\mu}g/mL$)-Am or Amx ($4{\mu}g/mL$).

• Tuberculosis and Respiratory Diseases
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• 제77권4호
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• pp.161-166
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• 2014

Since tuberculosis (TB) remains a major global health concern and the incidence of multi-drug resistant (MDR)-TB is increasing globally, new modalities for the detection of TB and drug resistant TB are needed to improve TB control. The Xpert MTB/RIF test can be a valuable new tool for early detection of TB and rifampicin resistance, with a high sensitivity and specificity. Late-generation fluoroquinolones, levofloxacin, and moxifloxacin, which are the principal drugs for the treatment of MDR-TB, show equally high efficacy and safety. Systemic steroids may reduce the overall TB mortality attributable to all forms of TB across all organ systems, although inhaled corticosteroids can increase the risk of TB development. Although fixed dose combinations were expected to reduce the risk of drug resistance and increase drug compliance, a recent meta-analysis found that they might actually increase the risk of relapse and treatment failure. Regarding treatment duration, patients with cavitation and culture positivity at 2 months of TB treatment may require more than 6 months of standard treatment. New anti-TB drugs, such as linezolid, bedaquiline, and delamanid, could improve the outcomes in drug-resistant TB. Nontuberculous mycobacterial lung disease has typical clinical and immunological phenotypes. Mycobacterial genotyping may predict disease progression, and whole genome sequencing may reveal the transmission of Mycobacterium abscessus. In refractory Mycobacterium avium complex lung disease, a moxifloxacin-containing regimen was expected to improve the treatment outcome.

• 약학회지
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• 제42권2호
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• pp.175-180
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• 1998

Bifidobacterium bifidum OFR9 that exhibits acquired resistance to rifampicin and fluoroquinolones was selected by MNNG and multi-step mutation method. To investigate the resistance mechanism to rifampicin in the strain, RNA polymerase from B. bifidum parent strain and rifampicin-resistance OFR9 was partially purified and its sensitivity to rifampicin was assayed. The profile of RNA polymerase preparation of B. bifidum parent and B. bifidum OFR9 is similar to that of E. coli RNA polymerase that includes the basic subunits of ${\beta}$`, ${\beta},\;{\sigma},\;{\alpha}$ but which are a little different in size when they are compared with E. coli RNA polymerase subunits. RNA polymerase isolated from the parent strain was inhibited by 1${\mu}$g/ml rifampicin but that from B. bifidum OFR9 was not affected by 100${\mu}$g/ml concentration of rifampicin. RNA polymerase activity of B. bifidum OFR9 was maintained over 90% through that rifampicin concentration. This result is consistent with MIC values of in vitro test. It can be concluded that the mechanism of rifampicin resistance in B. bifidum OFR9 is due to an alteration of RNA polymerase.

• Bulletin of the Korean Chemical Society
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• 제35권8호
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• pp.2317-2325
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• 2014

P-glycoprotein (P-gp) is a member of the ATP-Binding Cassette transporter superfamily and mediates transmembrane efflux of many drugs. Since it is involved in multi-drug resistance activity in various cancer cells, the development of P-gp inhibitor is one of the major concerns in anticancer therapy. Human P-gp protein has at least two "functional" drug binding sites that are called "H" site and "R" site, hence it has multi-binding-specificities. Though the amino acid residues that constitute in drug binding pockets have been proposed by previous experimental evidences, the shapes and the binding poses are not revealed clearly yet. In this study, human P-gp structure was built by homology modeling with available crystal structure of mouse P-gp as a template and docking simulations were performed with inhibitors such as verapamil, hoechst33342, and rhodamine123 to construct the interaction between human P-gp and its inhibitors. The docking simulations were performed 500 times for each inhibitor, and then the interaction frequency of the amino acids at the binding poses was analyzed. With the analysis results, we proposed highly contributing residues that constitute binding pockets of the human P-gp for the inhibitors. Using the highly contributing residues, we proposed the locations and the shapes of verapamil binding site and "R" site, and suggested the possible position of "H" site.

• 한국미생물·생명공학회지
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• 제51권4호
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• pp.432-440
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• 2023

Irrational and injudicious use of antibiotics, easy availability of them as over-the-counter drugs in economically developing countries, and unavailability of regulatory policies governing antimicrobial use in agriculture, animals, and humans, has led to the development of multi-drug resistance (MDR) bacteria. The use of medicinal plants can be considered as an alternative, with a consequent impact on microbial resistance. We tested extracts of Piper longum fruits as new natural products as agents for reversing the resistance to antibiotics. Six crude extracts of P. longum fruits were utilized against a clinical isolate of multidrug-resistant Staphylococcus aureus.The antibiotic susceptibility testing disc method was used in the antibiotic resistance reversal analysis. Apart from cefoxitin and erythromycin, all other antibiotics used (lincosamides [clindamycin], quinolones [levofloxacin and ciprofloxacin], and aminoglycosides [amikacin and gentamicin]) were enhanced by P. longum extracts. The extracts that showed the greatest synergy with the antibiotics were EAPL (ethyl acetate [extract of] P. longum), n-BPL (n-butanol [extract of] P. longum), and MPL (methanolic [extract of] P. longum The results of this study suggest that P. longum extracts have the ability to increase the effectiveness of different classes of antibiotics and reverse their resistance. However, future studies are needed to elucidate the molecular mechanisms behind the synergy between antibiotic and phytocompound(s) and identify the active biomolecules of P. longum responsible for the synergy in S. aureus.