Acquisition of five high-Mr penicillin-binding protein variants during transfer of high-level beta-lactam resistance from Streptococcus mitis to Streptococcus pneumoniae.
Penicillin-resistant isolates of Streptococcus pneumoniae generally contain mosaic genes encoding the low-affinity penicillin-binding proteins (PBPs) PBP2x, PBP2b, and PBP1a. We now present evidence that PBP2a and PBP1b also appear to be low-affinity variants and are encoded by distinct alleles in beta-lactam-resistant transformants of S. pneumoniae obtained with chromosomal donor DNA from a Streptococcus mitis isolate. Different lineages of beta-lactam-resistant pneumococcal transformants were analyzed, and transformants with low-affinity variants of all high-molecular-mass PBPs, PBP2x, -2a, -2b, -1a, and -1b, were isolated. The MICs of benzyl-penicillin, oxacillin, and cefotaxime for these transformants were up to 40, 100, and 50 microg/ml, respectively, close to the MICs for the S. mitis donor strain. Recruitment of low-affinity PBPs was accompanied by a decrease in cross-linked muropeptides as revealed by high-performance liquid chromatography of muramidase-digested cell walls, but no qualitative changes in muropeptide chemistry were detected. The growth rates of all transformants were identical to that of the parental S. pneumoniae strain. The results stress the potential for the acquisition by S. pneumoniae of high-level beta-lactam resistance by interspecies gene transfer.
Hakenbeck
R
R
Max-Planck Institut für Molekulare Genetik, Berlin, Germany. hakenb@rhrk.uni-kl.de
König
A
A
Kern
I
I
van der Linden
M
M
Keck
W
W
Billot-Klein
D
D
Legrand
R
R
Schoot
B
B
Gutmann
L
L
D000595:Amino Acid Sequence; D019881:Aminoacyltransferases; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D002439:Cefotaxime / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D006602:Hexosyltransferases; D008969:Molecular Sequence Data; D008970:Molecular Weight; D002267:Muramoylpentapeptide Carboxypeptidase / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D010403:Penicillin Resistance; D046915:Penicillin-Binding Proteins; D010453:Peptide Synthases; D010458:Peptidyl Transferases; D013291:Streptococcus / Q000187:drug effects* / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics; D014169:Transformation, Bacterial
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; C478699:penicillin-binding protein 2a, Streptococcus; D019881:Aminoacyltransferases; C478701:penicillin-binding protein 2b, Streptococcus; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D010453:Peptide Synthases; D002439:Cefotaxime