Involvement of Mutation in ampDI, mrcA, and at Least One Additional Gene in β-Lactamase Hyperproduction in Stenotrophomonas maltophilia

ABSTRACTIt has been reported that targeted disruption of ampDI or mrcAcauses β-lactamase hyperproduction in Stenotrophomonas maltophilia. We show here that β-lactamase-hyperproducing laboratory selected mutants and clinical isolates can have wild-type ampDI and mrcAgenes, implicating mutation of at least one additional gene in this phenotype. The involvement of mutations at multiple loci in the activation of β-lactamase production in S. maltophiliareveals that there are significant deviations from the enterobacterial paradigm of AmpR-mediated control of β-lactamase induction. We do show, however, that S. maltophiliaampDI can complement a mutation in Escherichia coliampD. This suggests that an anhydromuropeptide degradation product of peptidoglycan is used to activate AmpR in S. maltophilia, as is also the case in enteric bacteria.