Involvement of Mutation in ampD I, mrcA, and at Least One Additional Gene in -Lactamase Hyperproduction in

It has been reported that targeted disruption of ampD I ormrcA causes-lactamase hyperproduction in Stenotrophomonas maltophilia. We show here that-lactamase-hyperproducing laboratory selected mutants and clinical isolates can have wild-type ampD I andmrcA genes, implicating mutation of at least one additional gene in this phenotype. The involvement of muta-tions at multiple loci in the activation of -lactamase production in S. maltophilia reveals that there are significant deviations from the enterobacterial paradigm of AmpR-mediated control of -lactamase induction. We do show, however, that S. malto-philia ampD I can complement a mutation in Escherichia coli ampD. 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. Stenotrophomonas maltophilia is an important, emerging causeof soft tissue, ocular, bloodstream, and respiratory tract infec-tions in severely ill and/or immunocompromised patients and is increasingly being found colonizing the lungs of patients with cystic fibrosis. Members of this species are intrinsically multidrug resistant, with resistance to most -lactams and aminoglycosides being expressed by the majority of clinical isolates (1, 2). -Lac-tam resistance is due to the production of two -lactamase en-zymes, L1 and L2, which are coordinately upregulated durin