• Bulletin of the Korean Chemical Society
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• v.14 no.4
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• pp.491-496
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• 1993

A class A ${\beta}$-lactamase from Staphylococcus aureus PC1 complexed with 3R,5R-clavulanate is studied. The starting geometry for the computation is the crystal structure of the ${\beta}$-lactamase. Docking of the clavulanate to the enzyme is done exploiting the requirements of electrostatic and shape complementarity between the enzyme and clavulanate. This structure is then hydrated by water molecules and refined by energy minimization and short molecular dynamics simulation. In the energy refined structure of this complex, the carboxyl group of the clavulanate is hydrogen bonded to Lys-234, and the the carbonyl carbon atom of the clavulanate is adjacent to the $O_{\gamma}$ of Ser-70. It is found that a crystallographic water molecule initially located at the oxyanion hole, which is formed by the two -NH group of Ser-70 and Gln-237, is replaced by the carbonyl oxygen atom of the 3R,5R-clavulanate after docking and energy reginement. The crystallographic water molecules are proved to be important in ligand binding. Glu-166 residue is found to be repulsive to the binding of clavulanate, which is in agreement with experimental observation. Arg-244 residue is found to be important to the binding of clavulanate as well as to interaction with C2 side chain of the clavulanate. The electron density redistribution of the clavulanate on binding to the ${\beta}$-lactamase in studied by an ab initio quantum-mechanical calculation. A significant redistribution of electron density of the clavulanate is induced by the enzyme, toward the enzyme, toward the transition state of the enzymatic reaction.

• Journal of Veterinary Clinics
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• v.27 no.2
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• pp.125-129
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• 2010

A 2-year-old female Pomeranian dog was referred with multiple pelvic fractures. The surgical correction was performed for the fractures. However, after the surgery, purulent exudation was occurred in the surgical site. Antibiotic susceptibility test revealed that the isolated bacteria are resistant to penicillins, cephalosporins, aminoglycosides, quinolones, and trimethoprim/sulfamethoxazole. Bacterial identification and extended-spectrum $\beta$-lactamase (ESBL) confirming test indicated that the isolated bacteriae is ESBL-producing Klebsiella pneumoniae. Minimum inhibitory concentration (MIC) and maximum bactericidal concentration (MBC) tests revealed that meropenem, one of carbapenems, is the only effective antibiotic. The patient was treated with meropenem for 5 days. After 10 days, the exudation was disappeared and the infection was cured. The molecular typing of the ESBL revealed that TEM-1 ESBL is present in the bacteria isolated from the patient. The bacteria isolated from the owner's palm also revealed that TEM-1 and SHV-1 ESBLs are present.

• Korean Journal of Plant Resources
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• v.33 no.6
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• pp.578-585
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• 2020

This study was designed to assess the possibility of using medicinal plant extracts as β-lactamase inhibitors to control antibiotic-resistant Staphylococcus aureus. The susceptibilities of S. aureus ATCC 15564 (SA^WT), ciprofloxacininduced S. aureus ATCC 15564 (SA^CIP), oxacillin-induced S. aureus ATCC 15564 (SA^OXA), and clinically-isolated S. aureus CCARM 3008 (SA^CLI) to ampicillin were determined in the absence and presence of medicinal plant extracts, including Cleyera japonica (CJ), Carpinus laxiflora (CL), Euphorbia helioscopia (EH), Euscaphis japonica (EJ), Oenothera erythrosepala (OE), and Rosa multiflora (RM). The phenotypic change in the clear inhibition zones around ampicillin disc was observed for SA^WT, SA^CIP, and SA^OXA, indicating the production of ampicillinase. Compared to the controls, the MICs of ampicillin against SA^WT, SA^CIP, and SA^OXA were decreased from 4 to 0.5 ㎍/mL in the presence of CL, 16 to 4 ㎍/mL in the presence of RM, and 32 to 2 ㎍/mL in the presence of CL, EH, and RM, respectively. The medicinal plant extracts, OE, EJ, and CL, effectively inhibited the β-lactamase activities of SA^WT (78%), SA^CIP (57%), and SA^OXA (76%) when compared to the control. This results suggest that the medicinal plant extracts can be used as BLIs to control the antibiotic-resistant S. aureus.

• Korean Journal of Microbiology
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• v.40 no.4
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• pp.295-301
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• 2004

Recently, the rapid increase and global spread of extended-spectrum $\beta-lactamase$ producing clinical isolates has become a serious problem. The incidence of extended-spectrum $\beta-lactamase$ producing clinical isolates of Escherichia coli in Korea and susceptibility to antimicrobial agents were investigated. Total 233 isolates of E. coli were obtained from urine from hospitalized patients in Guro hospital, Korea University in 2001. One hun­dred and eighty four isolates $(78.9\%)$ were resistant to ampicillin, 80 isolates $(34.3\%)$ were resistant to ceph­alothin, 93 isolates $(39.9\%)$ were resistant to gentamicin, and 64 isolates $(27.5\%)$ were resistant to norfloxacin. Among 233 isolates, 17 isolates $(7.3\%)$ were positive as determined by the double disk synergy test. When min­imal inhibitory concentrations were assayed with additional 6 antimicrobial agents, 13 isolates $(76.5\%)$ were multi-drug resistant to at least four different class antimicrobial agents. Extended-spectrum $\beta-lactamase$ were characterized with isoelectric focusing gel electrophoresis and DNA sequencing. They were TEM-1 in 5 iso­lates, TEM-15 in 1 isolate, TEM-20 in 1 isolate, TEM-52 in 4 isolates, TEM-1 and AmpC in 2 isolates, TEM-1 and OXA-30 in 1 isolate, TEM-1 and OXA-33 in 1 isolate, TEM-1, CTX-M-3, and AmpC in 1 isolate, but SHV was not detected. Antimicrobial resistance genes were transferred to animal isolate of E. coli (CCARM No. 1203) by the filter mating method. Extended spectrum $\beta-lactamase$ producers studied in the current study have low correlation to each other as determined by random amplified polymorphic DNA and pulsed field gel elec­trophoresis. This is a contradictory result from the general hypothesis that extended-spectrum $\beta-lactamase$ pro­ducers in one hospital is a result from a clonal spread.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.161-161
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• 1996

10종의 6-exomethylene penamsulfone 유도체의 Type I, Type IV, TEM 효소에 대한 $\beta$-lactamase 저해 효과를 측정하였다. 7종의 합성 화합물은 Type I penicillinase에 대해서는 저해 효과가 없었으나, Type IV cephalosporinase에 대해서는 기존의 sulbactam이나 tazobactam에 비하여 강한 효과를 나타내었고, 특히 CH 1145는 tazobactam보다 약 30배 강한 활성을 보여주었다. CH 2140은 TEM 효소에 대하여 tazobactam과 유사한 저해효과를 보였다.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.43 no.6
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• pp.637-641
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• 2010

The antibiotics-resistance profiles of 28 strains of Vibrio parahaemolyticus isolated from seawater were investigated. All of the strains studied were resistant to ampicillin (100%), but susceptible to 12 other antibiotics. The minimum inhibitory concentration (MIC) of V. parahaemolyticus to ampicillin was as high as $1,024-2,048\;{\mu}g{\cdot}mL^{-1}$. The phenotype of strain 8 changed from ampicillin-resistant to susceptible with an in-frame deletion mutant of VPA0477, a putative ${\beta}$-lactamase gene, and the MIC for ampicillin of the mutant strain was $1{\mu}g{\cdot}mL^{-1}$. In conclusion, our findings suggest that the VPA0477 gene acts as a ${\beta}$-lactamase in ampicillin-resistant V. parahaemolyticus strains.

• Journal of Microbiology and Biotechnology
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• v.6 no.6
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• pp.369-374
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• 1996

The ${\beta}$-lactamase inhibitory protein (BLIP) produced by Streptomyces exfoliatus SMF19 was purified(33 kDa) and the N-terminal amino acid sequence was determined as NH2-ATSVVAWGGNND. Genomic DNA library of S. exfoliatus SMF19 was constructed in pWE15 and recombinants harbouring the corresponding gene were selected by colony hybridization to the mixture of 36-mer oligonucleotide designed from the N-terminal amino acid sequence. The corresponding gene (bliX) was isolated on a 4-kb ApaI fragment of S. exfoliatus SMF19 chromosomal DNA and then sequenced. The bliX consisting of 1, 119bp encoded a mature protein with a deduced amino acid sequence of 342 residues and also encoded a 40-amino-acid signal sequence. No significant sequence similarity to bliX was found by pairwise comparison using various protein and nucleotide sequences.

• YAKHAK HOEJI
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• v.47 no.6
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• pp.456-460
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• 2003

In vitro $\beta$-lactamase inhibitory activity of 6-exomethylenepenam compounds ( 1, 2, 3, 4 and 5) was compared with clavulanic acid, sulbactam and tazobactam. The inhibitory activity of compound 3 was stronger than those of sulbactam and clavulanic acid against Type I and II enzymes and stronger than tazobactam against Type III, IV, TEM enzymes. The inhibitory activity of 5 was stronger than sulbactam and clavulanic acid against Type I and II enzymes and stronger than tazobactam against Type III, and IV enzymes. The in vitro antimicrobial activity of 3, 4 and 5 combined with ampicillin and cefoperazone was compared with the sulbactam against $\beta$-lactamase producing 27 strains. But, synergistic activity of 3 and 5 was inferior to tazobactam.

• Proceedings of the Korean Society of Life Science Conference
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• 2000.09a
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• pp.88-88
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• 2000

• Korean Journal of Microbiology
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• v.40 no.2
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• pp.104-110
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• 2004

To determine evolution and genotype of new chromosomal AmpC $\beta$-lactamases among clinical isolates of Enterobacter species, we performed antibiotic susceptibility testing, pI determination, sequencing, and phy-logenetic analysis using developed expression/secretion vector. Six isolates have shown to produce AmpC $\beta$-lactamases. Six genes of AmpC $\beta$-lactamases that are responsible for the resistance to cephamycins (cefoxitin and cefotetan), amoxicillin, cephalothin, and amoxicillin-clavulanic acid were cloned and characterized in pMSG12119. Insert fragment containing the ampC genes was sequenced and found to have an open reading frame coding for 381-amino-acid $\beta$-lactamase. The nucleotide sequence of four ampC genes ($bla_EcloK992004.l$, $bla_EcloK995120.1$, $bla_EcloK99230$, and $bla_EareK9911729$) shared considerable homology with that of chromosomal ampC gene ($bla_EcloMHN1$) of E. cloacae MHN1 (more than 99.6% identity). The sequences of two ampC genes ($bla_EcloK9973$ and $bla_EcloK9914325$) showed close similarity to the chromosomal ampC gene ($bla_EcloQ908R$) of E. clo-acae 908R (99.7% identity). The results from phylogenetic analysis suggested that six ampC genes could be originated from $bla_EcloMHN1$ / or $bla_EcloQ908R$ / MIC patterns and exact pI values of six transformants indicated that the developed expression/secretion vector (pMSG1219) was suitable for the characterization of foreign genes in E. coli strain.