An aminoglycoside microarray platform for directly monitoring and studying antibiotic resistance

被引:29
作者
Disney, Matthew D.
Barrett, Olivia J.
机构
[1] Univ Buffalo, Dept Chem, Buffalo, NY 14260 USA
[2] Univ Buffalo, Ctr Excellence Bioinformat & Life Sci, Buffalo, NY 14260 USA
关键词
D O I
10.1021/bi701071h
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Antibiotic resistance is a major threat to human health. Since resistance to the aminoglycoside class of antibiotics is most commonly caused by enzymatic modification, we developed a high-throughput microarray platform for directly assaying resistance enzyme activity on aminoglycosides. After modification, the array can be hybridized with the therapeutic target, a bacterial rRNA A-site mimic, to study the effect that modification has on binding. Such studies will help identify important factors that contribute to high-affinity recognition of therapeutic targets and low-affinity recognition of and modification by resistance enzymes. This platform may also be useful for screening chemical libraries to discover new antibiotics that evade resistance.
引用
收藏
页码:11223 / 11230
页数:8
相关论文
共 39 条
[1]   Preparation of DNA and protein micro arrays on glass slides coated with an agarose film [J].
Afanassiev, Victor ;
Hanemann, Vera ;
Woelfl, Stefan .
NUCLEIC ACIDS RESEARCH, 2000, 28 (12) :E66
[2]   Chemical microarrays to identify ligands that bind pathogenic cells [J].
Barrett, Olivia J. ;
Childs, Jessica L. ;
Disney, Matthew D. .
CHEMBIOCHEM, 2006, 7 (12) :1882-1885
[3]   Chromosomal aadD2 encodes an aminoglycoside nucleotidyltransferase in Bacillus clausii [J].
Bozdogan, B ;
Galopin, S ;
Gerbaud, G ;
Courvalin, P ;
Leclercq, R .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2003, 47 (04) :1343-1346
[4]   Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics [J].
Carter, AP ;
Clemons, WM ;
Brodersen, DE ;
Morgan-Warren, RJ ;
Wimberly, BT ;
Ramakrishnan, V .
NATURE, 2000, 407 (6802) :340-348
[5]   Polytriazoles as copper(I)-stabilizing ligands in catalysis [J].
Chan, TR ;
Hilgraf, R ;
Sharpless, KB ;
Fokin, VV .
ORGANIC LETTERS, 2004, 6 (17) :2853-2855
[6]   Using selection to identify and chemical microarray to study the RNA internal loops recognized by 6′-N-acylated kanamycin A [J].
Disney, Matthew D. ;
Childs-Disney, Jessica L. .
CHEMBIOCHEM, 2007, 8 (06) :649-656
[7]   Aminoglycoside microarrays to explore interactions of antibiotics with RNAs and proteins [J].
Disney, MD ;
Seeberger, PH .
CHEMISTRY-A EUROPEAN JOURNAL, 2004, 10 (13) :3308-3314
[8]   Aminoglycoside microarrays to study antibiotic resistance [J].
Disney, MD ;
Magnet, S ;
Blanchard, JS ;
Seeberger, PH .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (12) :1591-1594
[9]   Characterization of an inexpensive, nontoxic, and highly sensitive microarray substrate [J].
Dufva, M ;
Petronis, S ;
Jensen, LB ;
Krag, C ;
Christensen, CBV .
BIOTECHNIQUES, 2004, 37 (02) :286-+
[10]   Substrate promiscuity of an aminoglycoside antibiotic resistance enzyme via target mimicry [J].
Fong, DH ;
Berghuis, AM .
EMBO JOURNAL, 2002, 21 (10) :2323-2331