OXA-type beta-lactamases

The OXA-type (oxacillin-hydrolysing) enzymes are widespread and have been m ostly described in Enterobacteriaceae and in P. aeruginosa. They usually co nfer resistance to amino- and ureidopenicillin and possess high-level hydro lytic activity against cloxacillin, oxacillin, and methicillin. Their activ ities are weakly inhibited by clavulanic acid but sodium chloride (NaCl) po ssesses a strong inhibition activity. Oxacillin-hydrolysing beta-lactamases belong to Ambler class D and thus possess an active serine site as classes A and C beta-lactamases. overall amino-acid identities between class D and class A or class C beta-lactamases is about 16%. Until now, 24 Ambler clas s D enzymes, named OXA-1 to OXA-22, AmpS and LCR-1, have been characterised , either by sequence and/or by biochemical analyses, but for none of them a three dimensional structure is yet available. While some oxacillinases pre sent a significant degree of amino-acid identity (for example, OXA-1 and OX A-4; OXA-10 (PSE-2) derivatives; OXA-2 and OXA-3), most of them are only we akly related (20% to 30% amino-acid identity). Oxacillinases usually displa y a restricted-spectrum phenotype. However extension of their spectrum towa rds oxyimino cephalosporins and/or imipenem has recently been observed most ly as a consequence of point mutations in OXA-2 or OXA-10 derivatives. Thei r frequent plasmid- and/or integron-location provide them a mean for a wide diffusion.