• Title/Summary/Keyword: Multi-Drug Resistance

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Molecular Target Therapy of AKT and NF-kB Signaling Pathways and Multidrug Resistance by Specific Cell Penetrating Inhibitor Peptides in HL-60 Cells

  • Davoudi, Zahra;Akbarzadeh, Abolfazl;Rahmatiyamchi, Mohammad;Movassaghpour, Ali Akbar;Alipour, Mohsen;Nejati-Koshki, Kazem;Sadeghi, Zohre;Dariushnejad, Hassan;Zarghami, Nosratollah
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.10
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    • pp.4353-4358
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    • 2014
  • Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.

Characterization of Verotoxin-producing Escherichia coli Isolated from Domestic Foods (국내 유통식품에서 분리된 Verotoxin 생성 Escherichia coli의 특성)

  • Kwak, Hyo-Shun;Cha, Jin;Kwang, Kil-Jin;Kim, Hun;Park, Sun-Hee;Kim, Chang-Min
    • Journal of Food Hygiene and Safety
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    • v.15 no.3
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    • pp.241-247
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    • 2000
  • The incidence of verotoxin-producing Escherichia coli(VTEC) was surveyed in domestic foods including hamburger, raw meats and vegetables from 1997 to 1999. The molecular biological characteristics of the isolates were analyzed. Three VTEC strain were isolated from 1,700 samples. Serotypes of those isolates were 0157 : H7, 026 H4, and 056 : Hl2, respectively. Serotype O26 : H4 produced VT I and VT II, and 055 Hl2 isolate produced VT I, however the 60 MDa plasmid DNA and eae gene were not found from both strains. One 0157 : H7 isolate produced VT II and harbour 60 MDa plasmid DNA, however eae gene was not found in the strain. Although they produced VT, it seemed that the virulence of two strains were relatively weak because of the lack of the eae gene. In addition, the serotype O157 : H7 isolate resistant to ampicillin and streptomycin, while isolates of serotype O26 : H4 and O55 : Hl2 were multi-resistant to antibiotics including ampicillin, carbenicillin , cephalothin, trimethoprim/sulfamethoxazole and tetracycline. Supernatants of cultures of all three isolates were showed cytotoxic effect to vero and HeLa cell

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Antibiotic Resistance Among Salmonella spp. Isolated from Feces of Patients with Acute Diarrhea in Gwangju Area, Korea, during 2000-2009 (2000년-2009년 광주 광역시 지역의 급성설사환자의 분변에서 분리한 살모넬라 균주에서의 항생제 내성률 조사)

  • Kim, Tae Sun;Kim, Min Ji;Kim, Sun Hee;Seo, Jin-Jong;Kee, Hye Young;Chung, Jae Keun;Kim, Eun Sun;Moon, Yong Woon;Ha, Dong Ryong;Kim, Min Kyeong;Lim, Suk Kyung;Nam, Hyang-Mi
    • Korean Journal of Microbiology
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    • v.49 no.2
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    • pp.118-125
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    • 2013
  • Antibiotic susceptibility was examined for 596 Salmonella isolates from patients with acute gastroenteritis during 2000-2009 in Gwangju area in South Korea. Of 16 antibiotics tested, ampicillin resistance (43%) was the most commonly observed resistance among the 596 Salmonella sp. isolates, followed by tetracycline (35.9%), nalidixic acid (31.5%), and chloramphenicol (26.2%). Antibiotic resistance varied among serotypes: The highest resistance of S. Enteritidis and S. Typhimurium was to ampicillin (51.1%) and tetracycline (77.9%), respectively. A total of 89 resistance patterns were observed, and 26% (155/596) of Salmonella isolates were susceptible to all antibiotics tested in this study. About 21% (127/596) and 15% (87/596) of the isolates were resistant to one and two antibiotics, respectively. The rest of Salmonella isolates (227/596, 38%) were resistant to three or more antibiotic agents. The highest multi-drug resistance (MDR) was observed in serotype S. Paratyphi B (76.5%), followed by S. Typhimurium (58.2%), and S. Enteritidis (40.2%). The most common resistance pattern of MDR isolates was ampicillin-chloramphenicol-nalidixic acid-ticarcillin (36/227, 15.8%), most of which (35/36, 97.2%) were S. Enteritidis.

Molecular Mechanism of ABC Transporter Mdr49A Associated with a Positive Cross-Resistance in Transgenic Drosophila (형질전환 초파리를 이용한 Mdr49A 유전자의 살충제 교차저항성 기능 구명)

  • Seong, Keon Mook;Pittendrigh, Barry R.
    • Korean journal of applied entomology
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    • v.59 no.4
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    • pp.341-348
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    • 2020
  • The ATP-binding cassette (ABC) transporter superfamily represents the largest transmembrane protein that transports a variety of substrates across extra- and intra-cellular membranes. In insects, the ABC transporter proteins play crucial roles in insecticide resistance. To date, no studies have investigated the involvement of ABC transporter gene for cross-resistance to insecticide chemistries. Here, we studied such possible mechanisms against six conventional insecticides using transgenic Drosophila melanogaster strains carrying Mdr49 transcript variant A. For the 91-R and 91-C strains of Drosophila melanogaster, although they have a common origin, 91-R has been intensely selected with DDT for over 60 years, while 91-C has received no insecticide selection. Our transgenic analyses showed that overexpression of 91-R-MDR49 transcript variant A along with three amino acid variations can yield a relatively low degree of cross-resistance to carbofuran (2.0~6.7-fold) and permethrin (2.5~10.5-fold) but did not show cross-resistance to abamectin, imidacloprid, methoxychlor, and prothiofos as compared to the Gal4-driver control strain without transgene expression. These results indicate that the overexpression of Mdr49A in itself leads to a cross-resistance and three amino acid changes have additional effects on positive cross-resistance to carbofuran and permethrin.

Species Transferability of Klebsiella pneumoniae Carbapenemase-2 Isolated from a High-Risk Clone of Escherichia coli ST410

  • Lee, Miyoung;Choi, Tae-Jin
    • Journal of Microbiology and Biotechnology
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    • v.30 no.7
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    • pp.974-981
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    • 2020
  • Sequence type 410 (ST410) of Escherichia coli is an extraintestinal pathogen associated with multi drug resistance. In this study, we aimed to investigate the horizontal propagation pathway of a high-risk clone of E. coli ST410 that produces Klebsiella pneumoniae carbapenemase (KPC). blaKPC-encoding E. coli and K. pneumoniae isolates were evaluated, and complete sequencing and comparative analysis of blaKPC-encoding plasmids from E. coli and K. pneumoniae, antimicrobial susceptibility tests, polymerase chain reaction, multilocus sequence typing, and conjugal transfer of plasmids were performed. Whole-genome sequencing was performed for plasmids mediating KPC-2 production in E. coli and K. pneumoniae clinical isolates. Strains E. coli CPEc171209 and K. pneumoniae CPKp171210 were identified as ST410 and ST307, respectively. CPEc171209 harbored five plasmids belonging to serotype O8:H21, which is in the antimicrobial-resistant clade C4/H24. The CPKp171210 isolate harbored three plasmids. Both strains harbored various additional antimicrobial resistance genes. The IncX3 plasmid pECBHS_9_5 harbored blaKPC-2 within a truncated Tn4401a transposon, which also contains blaSHV-182 with duplicated conjugative elements. This plasmid displayed 100% identity with the IncX3 plasmid pKPBHS_10_3 from the K. pneumoniae CPKp171210 ST307 strain. The genes responsible for the conjugal transfer of the IncX3 plasmid included tra/trb clusters and pil genes coding the type IV pilus. ST410 can be transmitted between patients, posing an elevated risk in clinical settings. The emergence of a KPC-producing E. coli strain (ST410) is concerning because the blaKPC-2-bearing plasmids may carry treatment resistance across species barriers. Transgenic translocation occurs among carbapenem-resistant bacteria, which may spread rapidly via horizontal migration.

Assessment of Bacterial Contamination and Antibiotic Resistance Patterns in Ready-To-Eat Side Dishes in Seoul Area, 2007 (2007년 서울 지역에서 판매되고 있는 반찬류의 세균 오염과 항생제 내성실태)

  • Kim, Mi-Jin;Lee, Do-Kyung;Jang, Seok;Yang, Hwan-Jin;An, Hyang-Mi;Baek, Eun-Hye;Ha, Nam-Joo
    • YAKHAK HOEJI
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    • v.52 no.6
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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.

Characteristics of Enterococcus faecium isolated from rough-toothed dolphin, Steno bredanensis (뱀머리돌고래, Steno bredanensis에서 분리된 Enterococcus faecium의 특성)

  • Kim, Myoung Sug;Choi, Hye Sung;Han, Hyun Ja;Kim, Doo Nam;An, Du Hae;Jung, Sung Hee
    • Journal of fish pathology
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    • v.26 no.3
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    • pp.289-294
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    • 2013
  • Enterococcus faecium was isolated from the internal organs of the rough-toothed dolphine, Steno bredanensis which was stranded at Jeju island. E. faecium were isolated from the liver, spleen, kidney, heart and lung up to $1.54{\times}10^6$ cfu/g. No significant differences of bacterial enzyme activities between E. faecium KCCM 12118 and the isolates were found. Biochemical constellation was the same or similar to that of E. faecium KCCM 12118 according to API20 strep. All isolates had the multi-drug resistance to 6 antibiotics by an agar disk diffusion method but these isolates didn't have resistance to chloramphenicol and vancomycin.

Emergence of Conjugative Multidrug-Resistant Pseudomonas aeruginosa (접합가능한다제내성녹농균의출현)

  • Miyoung Lee
    • Microbiology and Biotechnology Letters
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    • v.51 no.4
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    • pp.517-525
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    • 2023
  • The emergence and spread of multidrug-resistant Pseudomonas aeruginosa (MRPA) have become a serious problem worldwide. The involvement of metallo-β-lactamases (MBLs) in inducing carbapenem resistance is particularly acute. However, unlike other members of the Enterobacteriaceae genus, new clones of P. aeruginosa are constantly emerging and rapidly replacing previously prevalent dominant clones. Therefore, this study aimed to perform antimicrobial resistance gene analysis, integron gene cassette analysis using DNA sequencing, and plasmid transfer analysis by conjugation to investigate the antimicrobial resistance dynamics of 18 P. aeruginosa strains isolated from various medical samples at a general hospital in Busan from September 2017 to September 2019. All 18 strains showed extensively drug-resistant (XDR) phenotype and were resistant to most antibiotics, except colistin (100%) but were susceptible to aztreonam (22.2%) and ceftazidime (16.6%). Approximately 66.7% of the strains had Class 1 integrons showing various antimicrobial resistances. Notably, IMP-6 ST235 (66.7%), VIM-2 ST357 (16.7%), and IMP-1 ST446(16.7%) were identified. The identification of IMP-1-producing ST446, previously unreported in Korea, is noteworthy considering the emergence and prevalence of another MRPA high-risk clone.

Antibiotic Resistance of Escherichia Coli and Brevibacterium sp. Isolated from Livestock Waste and Disinfection Efficiency of Gamma-Ray Irradiation (축산폐기물에서 분리된 항생제 내성균 Escherichia coli....Brevibacterium sp.의 내성 특성 및 감마선 살균 효능)

  • Jang, Eun-Hee;Jung, Sang-Hyuk;Nam, Youn-Ku;Park, Woo-Shin;Lee, Myun-Joo;Kim, Tak-Hyun
    • Journal of Korean Society of Environmental Engineers
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    • v.32 no.7
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    • pp.676-681
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    • 2010
  • Antibiotic resistant bacteria were isolated from livestock wastes and the resistance patterns were investigated using various antibiotic agents. Also, a gamma ray was tested regarding the aspects of the effect on resistance pattern and the efficiency of disinfection. Among the isolates, Esherichia coli and Brevibacterium sp. showed the most serious resistance patterns. Esherichia coli had resistance against 9 agents whereas Brevibacterium sp. against 7 agents. It can be suggested from these results that the abuse of antibiotic agents will cause a serious mutation problem even to Esherichia coli which is ubiquitous in the ecosystem. Esherichia coli could be easily controlled but Brevibacterium sp. had a moderate resistance to the gamma ray under low doses. In the case of Brevibacterium sp, more than 2.0 kGy of a radiation dose will be required in order to achieve an enhanced efficiency of disinfection.

The distribution and antimicrobial susceptibility of pathogenic microorganisms isolated from chicken slaughtering and processing procedure (닭 도계 및 가공공정 중 유해미생물의 분포와 항생제 감수성)

  • Seol, Kuk-Hwan;Kim, Ki Hyun;Jo, Su-Mi;Kim, Young Hwa;Kim, Hyun-Wook;Ham, Jun-Sang
    • Korean Journal of Agricultural Science
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    • v.42 no.1
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    • pp.29-35
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    • 2015
  • This study was performed to analyze the distribution and antimicrobial resistance of pathogenic microorganisms isolated from the carcass and environments of chicken processing plant located in Gyeonggi province from October to November in 2010. Chicken slaughterhouse was visited 3 times and totally 40 samples were collected from chicken carcass before and after washing (n=14), chicken cuts (n=7), cooling water (n=8), brine (n=2), cutting knives (n=7) and working plate (n=2). Whole-chicken rinsing technique (for chicken carcasses) and swab technique (for working plate and knives) were used to analyze the distribution of pathogenic microorganisms. In addition, brine and chilling water from storage tanks were gathered using sterilized tubes and used as samples. The matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) for whole cell fingerprinting in combination with a dedicated bioinformatic software tool was used to identify the isolated microorganisms. The pathogenic microorganisms, such as Bacillus cereus (n=8) and Staphylococcus aureus (n=9), were isolated form the chicken processing process (chicken carcasses of before and after chilling, chicken cuts, and working plate). The antimicrobial susceptibility of those isolated microorganisms was analyzed using 21 antimicrobial agents. In the case of B. cereus, it showed 100% of resistance to subclasses of penicillins and peptides, and it also resistant to cephalothin, a member of critically important antimicrobials (CIA), however there was no resistance (100% susceptible) to vancomycin and chloramphenicol. S. aureus showed 100% resistance to subclasses of peptides and some of penicillins (penicillin and oxacillin), however, it showed 100% susceptibility to cephalosporins (cefazolin and cephalothin). All of the tested pathogens showed multi drug resistance (MDR) more than 4 subclasses and one of B. cereus and S. aureus showed resistance to 9 subclasses. After the ban on using the antimicrobials in animal feed in July 2011, there would be some change in microbial distribution and antimicrobial resistance, and it still has a need to be analyzed.