A proteolytic transmembrane signaling pathway and resistance to β-lactams in staphylococci

被引:165
作者
Zhang, HZ [1 ]
Hackbarth, CJ [1 ]
Chansky, KM [1 ]
Chambers, HF [1 ]
机构
[1] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Div Infect Dis, San Francisco, CA 94110 USA
关键词
D O I
10.1126/science.1055144
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
beta -Lactamase and penicillin-binding protein Za 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.
引用
收藏
页码:1962 / 1965
页数:4
相关论文
共 27 条
[1]  
[Anonymous], [No title captured]
[2]  
[Anonymous], 1988, Antibodies: A Laboratory Manual
[3]   DISSEMINATION AMONG STAPHYLOCOCCI OF DNA-SEQUENCES ASSOCIATED WITH METHICILLIN RESISTANCE [J].
ARCHER, GL ;
NIEMEYER, DM ;
THANASSI, JA ;
PUCCI, MJ .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (03) :447-454
[4]   BINDING OF BETA-LACTAM ANTIBIOTICS TO PENICILLIN-BINDING PROTEINS IN METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS [J].
CHAMBERS, HF ;
SACHDEVA, M .
JOURNAL OF INFECTIOUS DISEASES, 1990, 161 (06) :1170-1176
[5]   CONSTITUTIVE PENICILLINASE FORMATION IN STAPHYLOCOCCUS AUREUS OWING TO A MUTATION UNLINKED TO PENICILLINASE PLASMID [J].
COHEN, S ;
SWEENEY, HM .
JOURNAL OF BACTERIOLOGY, 1968, 95 (04) :1368-&
[6]   MOLECULAR ASPECTS OF METHICILLIN RESISTANCE IN STAPHYLOCOCCUS-AUREUS [J].
DELENCASTRE, H ;
DEJONGE, BLM ;
MATTHEWS, PR ;
TOMASZ, A .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1994, 33 (01) :7-24
[7]   ISOLATION OF MONOCLONAL-ANTIBODIES SPECIFIC FOR HUMAN C-MYC PROTO-ONCOGENE PRODUCT [J].
EVAN, GI ;
LEWIS, GK ;
RAMSAY, G ;
BISHOP, JM .
MOLECULAR AND CELLULAR BIOLOGY, 1985, 5 (12) :3610-3616
[8]   Studies of the repressor (Blal) of beta-lactamase synthesis in Staphylococcus aureus [J].
Gregory, PD ;
Lewis, RA ;
Curnock, SP ;
Dyke, KGH .
MOLECULAR MICROBIOLOGY, 1997, 24 (05) :1025-1037
[9]   BLAI AND BLAR1 REGULATE BETA-LACTAMASE AND PBP 2A PRODUCTION IN METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS [J].
HACKBARTH, CJ ;
CHAMBERS, HF .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1993, 37 (05) :1144-1149
[10]   ALTERED PRODUCTION OF PENICILLIN-BINDING PROTEIN 2A CAN AFFECT PHENOTYPIC-EXPRESSION OF METHICILLIN RESISTANCE IN STAPHYLOCOCCUS-AUREUS [J].
HACKBARTH, CJ ;
MIICK, C ;
CHAMBERS, HF .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (11) :2568-2571