Publication Date:
2001-03-10
Description:
beta-Lactamase and penicillin-binding protein 2a mediate staphylococcal resistance to beta-lactam antibiotics, which are otherwise highly clinically effective. Production of these inducible proteins is regulated by a signal-transducing integral membrane protein and a transcriptional repressor. The signal transducer is a fusion protein with penicillin-binding and zinc metalloprotease domains. The signal for protein expression is transmitted by site-specific proteolytic cleavage of both the transducer, which autoactivates, and the repressor, which is inactivated, unblocking gene transcription. Compounds that disrupt this regulatory pathway could restore the activity of beta-lactam antibiotics against drug-resistant strains of staphylococci.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, H Z -- Hackbarth, C J -- Chansky, K M -- Chambers, H F -- AI4005804/AI/NIAID NIH HHS/ -- AI46610/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2001 Mar 9;291(5510):1962-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Infectious Diseases, San Francisco General Hospital, Department of Medicine, University of California at San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11239156" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Motifs
;
Amino Acid Sequence
;
Anti-Bacterial Agents/metabolism/pharmacology
;
Bacterial Proteins/chemistry/metabolism
;
Carrier Proteins/chemistry/genetics/*metabolism
;
Catalysis
;
Cell Membrane/metabolism
;
Cloning, Molecular
;
DNA-Binding Proteins/chemistry/metabolism
;
Genes, Regulator
;
Metalloendopeptidases/chemistry/metabolism
;
Mutagenesis, Site-Directed
;
*Penicillin-Binding Proteins
;
Protein Structure, Tertiary
;
Recombinant Fusion Proteins/metabolism
;
Repressor Proteins/chemistry/genetics/*metabolism
;
*Signal Transduction
;
Staphylococcus aureus/*drug effects/genetics/*metabolism
;
Transformation, Bacterial
;
*beta-Lactam Resistance
;
beta-Lactamases/*biosynthesis
;
beta-Lactams
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
