• Proceedings of the PSK Conference
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• 2001.10a
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• pp.222.1-222.1
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• 2001

• Journal of Microbiology and Biotechnology
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• v.17 no.10
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• pp.1607-1615
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• 2007

We investigated the applicability of the TEM-l ${\beta}$-lactamase fragment complementation (BFC) system to develop a strategy for the screening of protein-protein interactions in bacteria. A BFC system containing a human Fas-associated death domain (hFADD) and human Fas death domain (hFasDD) was generated. The hFADD-hFasDD interaction was verified by cell survivability in ampicillin-containing medium and the colorimetric change of nitrocefin. It was also confirmed by His pull-down assay using cell lysates obtained in selection steps. A coiled-coil helix coiled-coil domain-containing protein 5 (CHCH5) was identified as an interacting protein of human uracil DNA glycosylase (hUNG) from the bacterial BFC cDNA library strategy. The interaction between hUNG and CHCH5 was further confirmed with immunoprecipitation using a mammalian expression system. CHCH5 enhanced the DNA glycosylase activity of hUNG to remove uracil from DNA duplexes containing a U/G mismatch pair. These results suggest that the bacterial BFC cDNA library strategy can be effectively used to identify interacting protein pairs.

• YAKHAK HOEJI
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• v.38 no.2
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• pp.140-148
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• 1994

${\beta}-Lactamase$ stability, chemotherapeutic activity, and pharmacokinetics of 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl]thiocarbonylthiomethyl-3-cephem-4-carboxylic acid(CEN1), 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyrimidyl)piperazinyl]thiocarbonylthiomethyl-3-cephem-4-carboxylic acid(CEN2), pivaloyloxymethyl-7-[(Z)-2-(2-aminothizaole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl]thiocarbonyl-thiomethyl-3-cephem-4-carboxylate(CEN1P), and pivaloyloxymethyl-7-{(Z)--2-(2-aminothizaole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl]thiocarbonyl-thiomethyl-3-cephem-4-carboxylate(CEN2P) were examined. CEN1, CEN2, CEN1P, and CEN2P were very stable to the ${\beta}-lactamase$ obtained from three strains(Enterobacter cloacae P99, Escherichia coli TEM, and Citrobacter freundii). Chemotherapeutic activities$(ED_{50})$ of CEN2 and CEN2P against experimental systemic infections due to Streptococcus pyogenes 77A and Escherichia coli 078 were superior to those of CEN1 and CEN1P, respectively. The $ED_{50}$ values of CEN1, CEN2 were 5.82 mg/kg, 0.89 mg/kg(s.c., S. pyogenes 77A) while those of CEN1P, CEN2P were 14.56mg/kg, 6.40mg/kg(p.o., S. pyogenes 77A), respectively. The pharmacokinetics of CEN1, CEN2, CEN1P, and CEN2P were investigated in mice and rats. In mice, peak blood levels of $1.25\;{\mu}g/ml$ were recorded within 20 min after oral administration of a single dose equivalent to 40 mg/kg CEN1P. Cmax of CEN1P was much higher than that of CEN1 in mice and rats. Oral absorption of CEN2P was much higher than that of CEN2.

• Biomedical Science Letters
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• v.13 no.4
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• pp.293-304
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• 2007

The emergence of extended spectrum $\beta$-lactamase (ESBL) producing bacteria is worldwide concern. Until recently, the most frequently identified strains in the Republic of Korea were E. coli and Klebsiella spp. The incidence of resistance to extended spectrum $\beta$-lactam antibiotics is increasing in Wonju city, Korea. Total 57 strains of ESBL producing E. coli and Klebsiella species were isolated from Wonju Christian Hospital during a 9 month-period from April to December, 2003. To determine the prevalence and genotypes of the ESBL producing clinical isolates, antibiotic susceptibility and ESBL activity test by VITEK system and double disk synergy (DDS) test, and PCR based genotyping were performed. Fourteen (82%) isolates of 17 ESBL producing E. coli were found to have $bla_{TEM}$ gene and 5 (29%) isolates were found to have $bla_{CTX-M}$ gene by polymerase chain reaction (PCR). Thirty (75%) isolates of 40 ESBL producing Klebsiella species with $bla_{TEM}$ gene, 38 (95%) isolates with $bla_{SHV}$ gene, and 7 (20%) isolates with $bla_{CTX-M}$ type gene were also identified. Enterobacterial repetitive intergenic consensus (ERIC) PCR and similarity index by dendrogram for genetical similarity to band pattern of each clinical isolates were examined. ESBL producing E. coli were grouped into 6 clusters up to 84% of similarity index and Klebsiella species were grouped into 12 clusters up to 76% of similarity index. In conclusion, ESBL producing clinical isolates were characterized with the results from antimicrobial resistance pattern and genetical similarity using ERiC PCR.

• Biomedical Science Letters
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• v.17 no.2
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• pp.135-140
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• 2011

We compared three EDTA-based phenotypic screening methods for detecting IMP-1 and VIM-2 type metallo-${\beta}$- lactamase (MBL)-producing isolates of Acinetobacter and Pseudomonas spp., EDTA-double disk synergy test (EDTADDST), Etest MBL, and imipenem (IPM)-EDTA disk test. A total of 183 isolates (65 Acinetobacter spp. and 118 Pseudomonas spp. showing IPM resistance), confirmed to MBL genes by PCR, were used. The criteria for MBL production were (i) presence of a synergistic zone between IPM and EDTA disks in EDTA-DDST, (ii) reduction of IPM minimal inhibitory concentration by ${\geq}$ 3 twofold dilutions in the presence of EDTA in the Etest MBL, and (iii) ${\geq}$ 7 mm increase in the inhibition zone around the IPM plus EDTA disks compared with a sole IPM disk in the IPM-EDTA disk test. In this study using 87 MBL-producing and 96 MBL-nonproducing isolates, the sensitivities/specificities of EDTA-DDST, Etest MBL and IPM-EDTA disk tests were 94.3/78.1%, 89.7/91.7%, and 97.7/95.8%, respectively. When the threshold for the increase of the inhibition zone around the IPM plus EDTA disk over a sole IPM disk was altered to ${\geq}$ 5 mm and ${\geq}$ 8 mm for Acinetobacter spp. and Pseudomonas spp., respectively, the sensitivity and specificity of the test were 98.9% and 96.9%, respectively. Of the three EDTA-based phenotypic tests, the IMP-EDTA disk test was superior for detection of MBL-producing isolates.

• YAKHAK HOEJI
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• v.41 no.1
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• pp.126-131
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• 1997

To overcome the problems of the resistance to clavulanic acid, many researchers are developing novel inhibitors that are not sensitive to new mutant ${\beta}$-lactamases. In order to evaluate newly synthesized compound CH2150 (Sodium (3S.5R)-6(Z)-[1-{1-(2-{2-benzoxazoly}thioethyl)-l.2,3-txiazol-4-yl}methylene] penicillanate-1,1-dioxide) as a ${\beta}$-lactamase inhibitor, we examined inhibitory activity of CH2150 against ${\beta}$-lactamases of clinical isolates resistant to ampicillin/sulbactam(12 strains of Escherichia coli and 13 strains of Staphylococcus aureus), and compared with that of sulbactam. Nitrocefin was used as substrate for ${\beta}$-lactamases, and the increase of absorbance was measured spectrophotometerically at 482 nm. ${\beta}$-Lactarnase inhibition of CH2150 against ${\beta}$-lactamases was 73 ~ 96% in E. coli and 76 ~ 79% in S. aureus. Comparatively, that of sulbactam was 96 ~ 100% and 96 ~ 100%, respectively. The inhibitory activity of CH2150 was slightly lower than that of sulbactam. The MIC values of ampicillin combined with CH2150 (2:1) for the clinical isolates were 4~512 ${\mu}$g/ml for E. coli and 1.0 ~ 64 ${\mu}$g/ml for S. aureus, whereas 0.5~16 ${\mu}$g/ml for E. coli and 0.25~8 ${\mu}$g/ml for S. aureus when combined with sulbactam (2:1).

• Tuberculosis and Respiratory Diseases
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• v.78 no.4
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• pp.371-374
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• 2015

Pulmonary pneumatoceles are air-filled thin-walled spaces within the lung and are rare in adult cases of pneumonia. We report the case of a 74-year-old male who was admitted with a cough and sputum production. He had been treated with oral dexamethasone since a brain tumorectomy 6 months prior. Contrast-enhanced computed tomography (CT) of the chest revealed a large pneumatocele in the right middle lobe and peripheral pneumonic consolidation. Bronchoalveolar lavage was performed; cultures identified extended-spectrum ${\beta}$-lactamase (ESBL) producing Proteus mirabilis. A 4-week course of intravenous ertapenem was administered, and the pneumatocele with pneumonia resolved on follow-up chest CT. To the best of our knowledge, this is the first reported case of pulmonary pneumatocele caused by ESBL-producing P. mirabilis associated with pneumonia.

• Journal of Microbiology and Biotechnology
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• v.27 no.9
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• pp.1716-1723
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• 2017

The rapid dissemination of extended-spectrum ${\beta}$-lactamase (ESBL)-producing Escherichia coli has significantly contributed to public health hazard globally. A total of 281 E. coli strains recovered from pigs and chickens between 2009 and 2015 in South Korea were analyzed for ESBL production. ESBL phenotypes were recognized in 14 E. coli isolates; ten and three ESBL-producing isolates carried only $bla_{CTX-M}$ and $bla_{CMY}$ genes, respectively, and one isolate harbored both genes. The predominant CTX-M and CMY types were CTX-M-15 (n = 8) and CMY-2 (n = 3). We also detected ESBL-producing isolates harboring $bla_{CTX-M-65}$, $bla_{CTX-M-14}$, $bla_{CMY-6}$, $bla_{DHA-1}$, and $bla_{TEM-1}$ genes. All ESBL-producing isolates showed resistance to the extent of the fourth generation cephalosporins, along with multidrug resistance. CTX-M-15-producing isolates showed higher MIC values than CTX-M-14- and CTX-M-65-producing isolates. The $bla_{CTX-M}$ and $bla_{CMY}$ genes have the potential to be transferable. The spreading of $bla_{CMY}$ and $bla_{CTX-M}$ genes was arbitrated mainly via Frep and IncI1 plasmids. Our isolates showed clonal diversity in PFGE analysis. This is the first report of E. coli isolates carrying $bla_{CMY-6}$ in chicken from South Korea. The emergence of CMY-6 ESBLs in a population of poultry suggests that extensive screening with long-term surveillance is necessary to prevent the dissemination of ESBL from chicken to human.

• Infection and chemotherapy
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• v.50 no.4
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• pp.357-361
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• 2018

While carbapenems are the drug of choice to treat extended-spectrum-${\beta}$-lactamase (ESBL)-producing strains, some alternative carbapenem-sparing regimens are suggested for antibiotic stewardship. We experienced a case of ciprofloxacin treatment failure for acute pyelonephritis caused by an apparently susceptible Escherichia coli. A 71-year-old woman presented the emergency department with fever for 7 days and bilateral flank pain for 2 days. The laboratory results and abdominopelvic computed tomography finding were compatible with acute pyelonephritis. During 3-day ciprofloxacin therapy, the patient remained febrile with persistent bacteremia. After the change in antibiotics to ertapenem, the patient's clinical course started to improve. ESBL-producing E. coli isolates were identified in all three consecutive blood samples. Pulsed-field gel electrophoresis (PFGE) patterns, serotypes, and sequence types showed the three isolates were derived from the identical strain. The isolates produced CTX-M-14 type ESBL belonging to the ST69 clonal group. Despite in vitro susceptibility, the failure was attributed to a gyrA point mutation encoding Ser83Leu within quinolone resistance-determining regions. This case suggests that ciprofloxacin should be used cautiously in the treatment of serious infections caused by ciprofloxacin-susceptible, ESBL-producing E. coli, even in acute pyelonephritis because in-vitro susceptibility tests could fail to detect certain genetic mutations.

• Childhood Kidney Diseases
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• v.25 no.1
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• pp.22-28
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• 2021

Purpose: The purpose of this study was to investigate the clinical outcomes of non-carbapenem treatment for urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) in young children. Methods: We retrospectively reviewed the medical records of children under 2 years of age who were diagnosed and treated for UTIs caused by ESBL-producing E. coli from September 2014 to March 2020. Results: Forty-three children under 2 years of age were treated with non-carbapenem antimicrobials for UTIs caused by ESBL-producing E. coli without bloodstream infections. The overall clinical and microbiological success rates for empirical antimicrobial treatment were 90.7% and 97.7%. Three of the patients (7.0%) experienced a relapse of UTI within a month. An in vitro susceptibility test showed that two patients were sensitive and one was resistant to the antimicrobial treatments. Furthermore, there were no significant differences in the time to defervescence, clinical success, microbiological success, and relapse rate between the susceptible (n=13) and non-susceptible groups (n=30). Conclusion: In this study, the overall relapse rate of patients treated with non-carbapenem antimicrobials was 7.0%. The patients showed high success rates in the clinical and microbiological responses to the non-carbapenems regardless of the results of the in vitro antimicrobial susceptibility test. These results provide evidence that non-carbapenems may be viable alternative treatments for UTIs caused by ESBL-producing E. coli.