Antimicrobial Agents and Chemotherapy, September 2001, p. 2407-2413, Vol. 45, No. 9
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
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
-Lactamases in Klebsiella
pneumoniae: Gene Evolution in Northern Taiwan and Two Novel
-Lactamases, SHV-25 and SHV-26
-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 (ThrACC
AlaGCC), L35Q (LeuCTA
GluCAA), and M129V
(MetATG
ValGTG) for SHV-25 and at position A187T (AlaGCC
ThrACC)
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
-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
-lactamase (ESBL) production in Taiwan. The
stepwise mutations that lead to a non-ESBL (SHV-25) and the
-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
-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.
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