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Antimicrobial Agents and Chemotherapy, September 2001, p. 2407-2413, Vol. 45, No. 9
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.9.2407-2413.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Diversity of SHV and TEM beta -Lactamases in Klebsiella pneumoniae: Gene Evolution in Northern Taiwan and Two Novel beta -Lactamases, SHV-25 and SHV-26

Feng-Yee Chang,1,* L. K. Siu,2 Chang-Phone Fung,3 Min-Hua Huang,1 and Monto Ho2

Division of Infectious Disease and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center,1 Division of Clinical Research, National Health Research Institute,2 and Section of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, and National Yang-Ming University,3 Taipei, Taiwan

Received 1 December 2000/Returned for modification 22 March 2001/Accepted 26 May 2001

A total of 113 blood culture isolates of Klebsiella pneumoniae from 10 hospitals in northern Taiwan were studied for SHV and TEM beta -lactamase production. blaSHV was amplified from all isolates by PCR. TEM-type resistance, was found in 32 of the isolates and was of the TEM-1 type in all isolates. SHV-1, -2, -5, -11, and -12 and two novel enzymes were identified. These novel enzymes were designated SHV-25 and SHV-26 and had pIs of 7.5 and 7.6, respectively. Amino acid differences in comparison to the amino acid sequence of blaSHV-1 were found at positions T18A (ThrACCright-arrowAlaGCC), L35Q (LeuCTAright-arrowGluCAA), and M129V (MetATGright-arrowValGTG) for SHV-25 and at position A187T (AlaGCCright-arrowThrACC) for SHV-26. The results of substrate profiles and MIC determinations showed that the novel enzymes did not hydrolyze extended-spectrum cephalosporins, rendering the isolates susceptible to these agents. Inhibition profiles revealed that the 50% inhibitory concentration for SHV-26 was higher than those for SHV-1 and SHV-25, resulting in an intermediate resistance to amoxicillin-clavulanic acid. Forty-nine ribotypes were identified, suggesting that major clonal spread had not occurred in any of the hospitals. According to the amino acid sequence, SHV beta -lactamases in Taiwan may basically be derived through stepwise mutation from SHV-1 or SHV-11 and further subdivided by four routes. The stepwise mutations initiated from SHV-1 or SHV-11 to SHV-2, SHV-5, and SHV-12 comprise the evolutionary change responsible for extended-spectrum beta -lactamase (ESBL) production in Taiwan. The stepwise mutations that lead to a non-ESBL (SHV-25) and the beta -lactamase (SHV-26) with reduced susceptibility to clavulanic acid are possibly derived from SHV-11 and SHV-1, respectively. The results suggest a stepwise evolution of SHV beta -lactamases in Taiwan.


* Corresponding author. Mailing address: Division of Infectious Disease and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Kung Rd., Sec. 2, Neihu, Taipei, 114, Taiwan. Phone: 886-2-87927257. Fax: 886-2-87927258. E-mail: fychang{at}ndmctsgh.edu.tw.


Antimicrobial Agents and Chemotherapy, September 2001, p. 2407-2413, Vol. 45, No. 9
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.9.2407-2413.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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