Abnormal physiological properties and altered cell wall composition in Streptococcus pneumoniae grown in the presence of clavulanic acid.
Subinhibitory concentrations of clavulanate caused premature induction of stationary-phase autolysis, sensitization to lysozyme, and reductions in the MICs of deoxycholate and penicillin for Streptococcus pneumoniae. In the range of clavulanate concentrations producing these effects, this beta-lactam compound was selectively bound to PBP 3. Cell walls isolated from pneumococci grown in the presence of clavulanate showed increased sensitivity to the hydrolytic action of purified pneumococcal autolysin in vitro. High-performance liquid chromatography analysis of the peptidoglycan isolated from the clavulanate-grown cells showed major qualitative and quantitative changes in stem peptide composition, the most striking feature of which was the accumulation of peptide species carrying intact D-alanyl-D-alanine residues at the carboxy termini. The altered biological and biochemical properties of the clavulanate-grown pneumococci appear to be the consequences of suppressed D,D-carboxypeptidase activity.
Severin
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A
Rockefeller University, New York, New York 10021, USA.
Severina
E
E
Tomasz
A
A
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology*; D003840:Deoxycholic Acid / Q000494:pharmacology; D004357:Drug Synergism; D006602:Hexosyltransferases; D006868:Hydrolysis; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009113:Muramidase / Q000378:metabolism; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D010399:Penicillin Amidase / Q000494:pharmacology; D010403:Penicillin Resistance; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000494:pharmacology; D010457:Peptidoglycan / Q000378:metabolism; D010458:Peptidyl Transferases; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002756:Cholagogues and Choleretics; D002969:Clavulanic Acids; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D010457:Peptidoglycan; D003840:Deoxycholic Acid; D019818:Clavulanic Acid; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D009113:Muramidase; D002267:Muramoylpentapeptide Carboxypeptidase; D010399:Penicillin Amidase