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.