國家衛生研究院 NHRI:Item 3990099045/1989
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    題名: High-level expression of AmpC beta-lactamase due to insertion of nucleotides between-10 and-35 promoter sequences in Escherichia coli clinical isolates: Cases not responsive to extended-spectrum-cephalosporin treatment
    其他題名: High-Level Expression of AmpC ß-Lactamase Due to Insertion of Nucleotides between -10 and -35 Promoter Sequences in Escherichia coli Clinical Isolates: Cases Not Responsive to Extended-Spectrum-Cephalosporin Treatment
    作者: Siu, LK;Lu, PL;Chen, JY;Lin, FM;Chang, SC
    貢獻者: Division of Clinical Research
    摘要: Two Escherichia coli isolates were recovered from the blood of two cancer patients and were demonstrated to produce high levels of the AmpC beta-lactamase with isoelectric points of >9.0. The hypertranscription of ampC RNA was observed by Northern blot hybridization in both isolates. One isolate (isolate EC44) had a point mutation (G-->A at position -28) and insertion of thymidine between positions -20 and -19 of the ampC promoter gene (GenBank accession no. AE000487). The single nucleotide insertion of T between positions -19 and -20 created an optimal distance (17 bp) in the Pribnow box for ampC hyperproduction. The other isolate (isolate EC38) had two point mutations (G-->A at position -28 and C-->T at position +58) and a 2-base (GT) insertion between positions -14 and -15. Although the insertion of GT between positions -14 and -15 may create a new promoter next to the original promoter, cloning of the ampC region with truncated nucleotides of the original -35 region of EC38 failed to verify the hypothesis that a new promoter would be created by such a nucleotide insertion. Instead, multiple start sites for ampC transcription at -1, +1, +2, and +3 were observed in an S1 nuclease protection assay. These results suggest that the RNA polymerase is flexible in the selection of a start site in ampC hypertranscription. In conclusion, nucleotide insertions between the -35 and -10 ampC promoter sequences was the mechanism for the hyperproduction of AmpC P-lactamase and resistance to oxyimino-cephalosporins. The failure of the two patients to respond to treatment with oxyimino-cephalosporins highlights the important role of such a resistance mechanism in the clinical setting.
    關鍵詞: Microbiology;Pharmacology & Pharmacy
    日期: 2003-07
    關聯: Antimicrobial Agents and Chemotherapy. 2003 Jul;47(7):2138-2144.
    Link to: http://dx.doi.org/10.1128/AAC.47.7.2138-2144.2003
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0066-4804&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000183786700012
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0038338397
    顯示於類別:[蕭樑基] 期刊論文

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