Article (Scientific journals)
Nucleotide sequences of the pbpX genes encoding the penicillin-binding proteins 2x from Streptococcus pneumoniae R6 and a cefotaxime-resistant mutant, C506
Laible, G.; Hakenbeck, R.; Sicard, M. A. et al.
1989In Molecular Microbiology, 3 (10), p. 1337-1348
Peer Reviewed verified by ORBi
 

Files


Full Text
LAIBLE_1989_nucleotides-sequence.pdf
Publisher postprint (5.39 MB)
Download

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
amino acid sequence; aminoacyltransferases; bacterial proteins; base sequence; carrier proteins/analysis/*genetics; cefotaxime/*metabolism; drug resistance, microbial/genetics; escherichia coli proteins; hexosyltransferases; molecular sequence data; muramoylpentapeptide carboxypeptidase/analysis/*genetics; mutation; penicillin-binding proteins; penicillins/metabolism; peptidoglycan glycosyltransferase; peptidyl transferases; restriction mapping; sequence homology, nucleic acid; serine-type d-ala-d-ala carboxypeptidase; streptococcus pneumoniae; transformation, genetic
Abstract :
[en] Development of penicillin resistance in Streptococcus pneumoniae is due to successive mutations in penicillin-binding proteins (PBPs) which reduce their affinity for beta-lactam antibiotics. PBP2x is one of the high-Mr PBPs which appears to be altered both in resistant clinical isolates, and in cefotaxime-resistant laboratory mutants. In this study, we have sequenced a 2564 base-pair chromosomal fragment from the penicillin-sensitive S. pneumoniae strain R6, which contains the PBP2x gene. Within this fragment, a 2250 base-pair open reading frame was found which coded for a protein having an Mr of 82.35kD, a value which is in good agreement with the Mr of 80-85 kD measured by SDS-gel electrophoresis of the PBP2x protein itself. The N-terminal region resembled an unprocessed signal peptide and was followed by a hydrophobic sequence that may be responsible for membrane attachment of PBP2x. The corresponding nucleotide sequence of the PBP2x gene from C504, a cefotaxime-resistant laboratory mutant obtained after five selection steps, contained three nucleotide substitutions, causing three amino acid alterations within the beta-lactam binding domain of the PBP2x protein. Alterations affecting similar regions of Escherichia coli PBP3 and Neisseria gonorrhoeae PBP2 from beta-lactam-resistant strains are known. The penicillin-binding domain of PBP2x shows highest homology with these two PBPs and S. pneumoniae PBP2b. In contrast, the N-terminal extension of PBP2x has the highest homology with E. coli PBP2 and methicillin-resistant Staphylococcus aureus PBP2'. No significant homology was detected with PBP1a or PBP1b of Escherichia coli, or with the low-Mr PBPs.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Laible, G.;  Max-Planck Institut fur Molekulare Genetik
Hakenbeck, R.;  Max-Planck Institut fur Molekulare Genetik
Sicard, M. A.;  Université Paul Sabatier - Toulouse 3 - UPS
Joris, Bernard ;  Université de Liège - ULiège > Departement de Microbiologie
Ghuysen, Jean-Marie ;  Université de Liège - ULiège > Departement de Microbiologie
Language :
English
Title :
Nucleotide sequences of the pbpX genes encoding the penicillin-binding proteins 2x from Streptococcus pneumoniae R6 and a cefotaxime-resistant mutant, C506
Publication date :
01 October 1989
Journal title :
Molecular Microbiology
ISSN :
0950-382X
eISSN :
1365-2958
Publisher :
Blackwell Publishing, Oxford, United Kingdom
Volume :
3
Issue :
10
Pages :
1337-1348
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FRSM - Fonds de la Recherche Scientifique Médicale [BE]
Available on ORBi :
since 07 January 2011

Statistics


Number of views
70 (0 by ULiège)
Number of downloads
196 (0 by ULiège)

Scopus citations®
 
91
Scopus citations®
without self-citations
57
OpenCitations
 
89

Bibliography


Similar publications



Contact ORBi