Introduction of an AmpR-L2 intergenic segment attenuates the induced beta-lactamase activity of Stenotrophomonas maltophilia.
Expression of the L1 and L2 beta-lactamase genes is generally regulated by a LysR type regulator of the AmpR in Stenotrophomonas maltophilia. The ampR gene is located immediately upstream of L2 and is transcribed divergently, forming an ampR-L2 module. The ampR-L2 modules of 16 S. maltophilia isolates were analyzed, revealing that the ampR-L2 intergenic (IG) regions show a significant genetic diversity, whereas AmpR proteins are highly conserved. The induction potential of the different AmpR toward the different ampR-L2 IG regions was evaluated by introducing the various IG-xylE transcriptional fusion constructs into a wild S. maltophilia strain. The induction levels achieved in the various AmpR-IG pairs display quantitative differences; meanwhile, the host beta-lactamase activity, in some cases, is attenuated by the introduced IG segment. Similar beta-lactamase attenuation phenomenon was observed in Enterobacter cloacae with an ampR-L2 IG segment of S. maltophilia. A concept of oligonucleotides attenuator for the development of an antimicrobial agent is proposed.
Chang
Y-C
YC
Department of Veterinary Medicine, National Chung-Hsing University, Taichung, 402, Taiwan, People's Republic of China.
Huang
Y-W
YW
Chiang
K-H
KH
Yang
T-C
TC
Chung
T-C
TC
D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D021901:DNA, Intergenic; D016972:Enterobacter cloacae / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010802:Phylogeny; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D020615:Stenotrophomonas maltophilia / Q000201:enzymology* / Q000235:genetics*; D001618:beta-Lactamases / Q000096:biosynthesis*
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D021901:DNA, Intergenic; C071526:AmpR protein, Bacteria; C425104:beta-lactamase L2; D001618:beta-Lactamases
Antimicrob Agents Chemother. 2001 Feb;45(2):413-9
11158734
Res Microbiol. 2009 Mar;160(2):152-8
19071216
Mol Microbiol. 2007 Oct;66(2):410-27
17854404
Int J Syst Bacteriol. 1999 Oct;49 Pt 4:1749-60
10555357
Annu Rev Microbiol. 1993;47:597-626
8257110
EMBO J. 1986 Dec 20;5(13):3709-14
3030737
Antimicrob Agents Chemother. 2008 Apr;52(4):1525-8
18212097
Cell. 1997 Mar 21;88(6):823-32
9118225
Proc Natl Acad Sci U S A. 1985 Jul;82(14):4620-4
2991883
Biochem J. 1990 Dec 15;272(3):627-31
2125210