title: Staphylococcus aureus penicillin-binding protein 4 and intrinsic beta-lactam resistance.
abstract: Increased levels of production of penicillin-binding protein PBP 4 correlated with in vitro acquired intrinsic beta-lactam resistance in a mutant derived from a susceptible strain of Staphylococcus aureus, strain SG511 Berlin. Truncation of the PBP 4 C-terminal membrane anchor abolished the PBP 4 content of cell membrane preparations as well as the resistance phenotype. A single nucleotide change and a 90-nucleotide deletion, comprising a 14-nucleotide inverted repeat in the noncoding pbp4 gene promoter proximal region, were the only sequence differences between the resistant mutant and the susceptible parent. These mutations were thought to be responsible for the observed overproduction of PBP 4 in the intrinsically beta-lactam-resistant mutant. The pbp4 gene was flanked upstream by the open reading frame abcA, coding for an ATP-binding cassette transporter-like protein showing similarities to eukaryotic multidrug transporters and downstream by a glycerol 3-phosphate cytidyltransferase (tagD)-like open reading frame presumably involved in teichoic acid synthesis. The abcA-pbp4-tagD gene cluster was located in the SmaI-D fragment in the S. aureus 8325 chromosome in close proximity to the RNA polymerase gene rpoB.
authors.affiliation: Institute of Medical Microbiology, University of Zürich, Switzerland.
authors.forename: U U
authors.initials: UU
authors.lastname: Henze
authors.forename: B
authors.initials: B
authors.lastname: Berger-Bächi
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000032:analysis; D005798:Genes, Bacterial; D006602:Hexosyltransferases; D016106:Methicillin Resistance / Q000235:genetics*; D008969:Molecular Sequence Data; D002267:Muramoylpentapeptide Carboxypeptidase / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D016366:Open Reading Frames; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism; D010458:Peptidyl Transferases; D010957:Plasmids; D015183:Restriction Mapping; D013211:Staphylococcus aureus / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D018440:beta-Lactam Resistance / Q000235:genetics; D047090:beta-Lactams
chemical_list: D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D004269:DNA, Bacterial; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D047090:beta-Lactams; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase