Imperial College London
Alternate

Professor Brian G Spratt FRS

Faculty of Medicine, School of Public Health

Emeritus Professor
 
 
 
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Contact

 

+44 (0)20 7594 3625b.spratt

 
 
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Location

 

G30Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{COFFEY:1995:10.1128/AAC.39.6.1306,
author = {COFFEY, TJ and DANIELS, M and MCDOUGAL, LK and DOWSON, CG and TENOVER, FC and SPRATT, BG},
doi = {10.1128/AAC.39.6.1306},
journal = {Antimicrobial Agents and Chemotherapy},
pages = {1306--1313},
title = {Genetic Analysis of Clinical Isolates of Streptococcus pneumoniae withHigh-Level Resistance to Expanded-Spectrum Cephalosporins},
url = {http://dx.doi.org/10.1128/AAC.39.6.1306},
volume = {39},
year = {1995}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Streptococcus pneumoniae CS109 and CS111 were isolated in the United States in 1991 and have high levelsof resistance to expanded-spectrum cephalosporins (MICs of 8 and 32 mg of cefotaxime per ml, respectively).CS109, but not CS111, also showed high-level resistance to penicillin. As both strains expressed the serotype23F capsule, were very closely related in overall genotype, and possessed identical or closely related mosaicpbp1a, pbp2x, and pbp2b genes, it is likely that they have arisen from a recent common ancestor. High-levelresistance to expanded-spectrum cephalosporins was entirely due to alterations of penicillin-binding proteins(PBPs) 1a and 2x, since a mixture of the cloned pbp1a and pbp2x genes from the resistant strains couldtransform the susceptible strain R6 to the full level of cephalosporin resistance of the clinical isolates. BothPBP1a and PBP2x of these strains were more resistant to inhibition by cephalosporins than those of typicalhighly penicillin-resistant isolates. The pbp1a genes of CS109 and CS111 were identical in sequence, and thefourfold difference in their levels of resistance to cephalosporins was due to a Thr-5503Ala substitution at theresidue following the conserved Lys-Ser-Gly motif of PBP2x. This substitution was also the major cause of the16-fold-lower resistance of CS111 to penicillin. The pbp2x gene of CS111, in an appropriate genetic background,could provide resistance to 16 mg of cefotaxime per ml but only to 0.12 mg of benzylpenicillin per ml. Removalof the codon 550 mutation resulted in a pbp2x gene that provided resistance to 4 mg of cefotaxime per ml and4 mg of benzylpenicillin per ml. The Thr-5503Ala substitution in CS111 therefore appears to provide increasedresistance to expanded-spectrum cephalosporins but a loss of resistance to penicillin.
AU  - COFFEY,TJ
AU  - DANIELS,M
AU  - MCDOUGAL,LK
AU  - DOWSON,CG
AU  - TENOVER,FC
AU  - SPRATT,BG
DO  - 10.1128/AAC.39.6.1306
EP  - 1313
PY  - 1995///
SN  - 1098-6596
SP  - 1306
TI  - Genetic Analysis of Clinical Isolates of Streptococcus pneumoniae withHigh-Level Resistance to Expanded-Spectrum Cephalosporins
T2  - Antimicrobial Agents and Chemotherapy
UR  - http://dx.doi.org/10.1128/AAC.39.6.1306
UR  - http://hdl.handle.net/10044/1/30586
VL  - 39
ER  -
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