Disease relevance of OXA-1

• Positive associations were found between E. coli and TEM-1 or OXA-1 and between K. pneumoniae and SHV-1 [1].
• The Bush type 2c and 2d enzymes OXA-1, OXA-2, PSE-1, PSE-2, and PSE-4 did not hydrolyze LJC 10,627, nor did the beta-lactamases of Staphylococcus aureus, Moraxella spp., Bacteroides fragilis, and Proteus vulgaris [2].
• Four types of beta-lactamases consisting of a penicillinase type I (TEM-1), a penicillinase type II (OXA-1), a cephalosporinase of Citrobacter freundii, and a cephalosporinase of Proteus vulgaris were introduced into Escherichia coli MC4100 and its omp mutants, MH1160 (MC4100 ompR1) and MH760 (MC4100 ompR2), by transformation [3].
• AmpS is predicted to be a mature protein of 27 kDa with a pI value of 7.9 that mostly closely resembles BLAD from Klebsiella pneumoniae (42.2%), and OXA-1 from Escherichia coli (36.6%), beta-lactamases that are encoded by genes carried on multiresistant transposons [4].
• None of the probes hybridized with genes for any of eight oxacillin-hydrolysing enzymes, PSE-2, OXA-1 to OXA-7, ROB-1 and chromosomal beta-lactamases of various Enterobacteriaceae (except Klebsiella pneumoniae) and Pseudomonas aeruginosa [5].

High impact information on OXA-1

• The 5' flanking regions of two other genes, the trimethoprim-resistance gene from R388 and the gentamicin resistance (aadB) gene from pDGO100, are greater than 98% homologous to the 5' flanking sequences of the OXA-1, OXA-2, and aadA genes until they diverge at the target sequence [6].
• The OXA-1 beta-lactamase gene is part of Tn2603, which is borne on the R plasmid RGN238 [6].
• We report here the complete nucleotide sequence of the OXA-1 beta-lactamase gene and flanking sequences [6].
• Analysis of 5' and 3' flanking sequences shows that Tn2603 differs from its probable precursor, Tn21, by a precise 1004-base-pair insertion, containing the OXA-1 structural gene, at the target sequence AAAGTT, which is located between the Tn21 streptomycin/spectinomycin (aadA) promoter and its structural gene [6].
• Precise insertion of antibiotic resistance determinants into Tn21-like transposons: nucleotide sequence of the OXA-1 beta-lactamase gene [6].

Chemical compound and disease context of OXA-1

• TEM-1- and OXA-1-positive isolates were always Escherichia coli and represented 86 and 8%, respectively, of the ampicillin-resistant isolates of this species [7].
• A member of the class D family of serine beta-lactamases, OXA-1 is especially active against the penicillins oxacillin and cloxacillin and is now found in 10% of E. coli clinical isolates [8].
• Interestingly, a decrease in cefuroxime susceptibility in Escherichia coli occurred in a few OXA-1 producing strains as well as in strains that produced only chromosomal beta-lactamase [9].
• The permeability coefficient of cefetamet was measured in E. coli C600 carrying a pUC18 plasmid derivative, in which the gene of a transferable cephamycinase (CMY-2) was cloned, whereas diffusion of cefixime and cefuroxime was measured in E. coli C600 harbouring the OXA-1 beta-lactamase gene [10].

Biological context of OXA-1

• AsbB1 was a class D enzyme most closely related to the oxacillin-hydrolyzing enzyme OXA-1, with 34% amino acid sequence identity [11].
• OXA-47 had a narrow spectrum of hydrolysis activity and did not hydrolyze ceftazidime or imipenem, as is found for the beta-lactamase (OXA-1) to which it is related [12].
• All but 1 of the 33 E. coli phenotypes found to be TEM-1 positive were uniformly positive for the beta-lactamase gene, whereas some of the phenotypes found to be positive for OXA-1 (2 of 3) and SHV-1 (6 of 70) were occasionally negative for the respective genes [7].
• In contrast to the structures of OXA-2, OXA-10, and OXA-13 belonging to other subclasses, the OXA-1 molecule is monomeric rather than dimeric and represents the subclass characterized by an enlarged Omega loop near the beta-lactam binding site [13].
• The combined data indicate that YidC is targeted by the signal recognition particle and inserts at the SecAYEG-YidC translocon early during biogenesis, unlike its mitochondrial homologue Oxa1p [14].

Anatomical context of OXA-1

• However, to integrate mitochondrial translation products into the inner membrane of mitochondria, the ribosome-binding domain of Oxa1 has to be appended onto YidC [15].
• We, furthermore, find no evidence for the involvement of known membrane-bound translocation apparatus; proteolysis of thylakoids destroys the Sec and Tat translocons but does not block PsaK insertion, and antibodies against the Oxa1/YidC homolog, Alb3, block the SRP-dependent insertion of Lhcb1 but again have no effect on PsaK insertion [16].

Associations of OXA-1 with chemical compounds

• We propose the designation Tn1404 for this unit, which, like transposons carrying OXA-1, PSE-1, PSE-4, and some transposons determining TEM-1, includes genes for beta-lactam, aminoglycoside, and sulfonamide resistance [17].
• PSE-2 beta-lactamase resembled other PSE enzymes in activity against carbenicillin, but it also resembled OXA enzymes, such as OXA-1, in rapid hydrolysis of oxacillin, cloxacillin, and methicillin and in inhibition by sodium chloride but not by cloxacillin [17].
• Bacteria possessing TEM-1-like beta-lactamases are generally regarded as susceptible to ampicillin-sulbactam (SAM), while those harboring OXA-1 enzymes are considered resistant [18].
• Ceftibuten was found to be very stable in the presence of five commonly occurring beta-lactamases of both the chromosomal-mediated (P99, K1) and plasmid-mediated (CARB-2, OXA-1, TEM-1) types [19].
• Cefpodoxime and the other methoxyimino cephalosporins exhibited a poor affinity to the plasmid-mediated TEM-2 and OXA-1 enzymes [20].

Other interactions of OXA-1

• Isolates producing either AmpC or OXA-1 enzymes or producing high levels of TEM-1 beta-lactamases had susceptibility patterns that were difficult to distinguish without IEF and/or amplification of the corresponding specific genes [21].

Analytical, diagnostic and therapeutic context of OXA-1

• Crystallization and preliminary X-ray study of OXA-1, a class D beta-lactamase [8].
• Molecular cloning of DNA fragments between 1.5 and 8 kb from BamHI, EcoRI, HindIII, SalI, or Sau3A digests permitted the isolation of structural genes coding for TEM-1, ROB-1, OXA-1, OXA-3, OXA-4, OXA-5, PSE-1, PSE-2, PSE-3, PSE-4, CARB-3, CARB-4, AER-1, and LCR-1 beta-lactamases [22].
• The production of TEM 1, OXA 2, CARB 3 and PSE 1 beta-lactamases had no influence on susceptibility to the antibiotic, whereas the synthesis of TEM 2, SHV 1 and OXA 1 beta-lactamases increased minimum inhibitory concentrations (MIC) by 2-4 times [23].
• Furthermore, the antibody induced change in enzymic activity of various beta-lactamases was demonstrated by activity titration curves for TEM 1, TEM 2, OXA 1, OXA 2, OXA 3 beta-lactamases from E. coli [24].

References