title: Burkholderia pseudomallei class a beta-lactamase mutations that confer selective resistance against ceftazidime or clavulanic acid inhibition.
abstract: Burkholderia pseudomallei, the causative agent of melioidosis, is inherently resistant to a variety of antibiotics including aminoglycosides, macrolides, polymyxins, and beta-lactam antibiotics. Despite resistance to many beta-lactams, ceftazidime and beta-lactamase inhibitor-beta-lactam combinations are commonly used for treatment of melioidosis. Here, we examine the enzyme kinetics of beta-lactamase isolated from mutants resistant to ceftazidime and clavulanic acid inhibition and describe specific mutations within conserved motifs of the beta-lactamase enzyme which account for these resistance patterns. Sequence analysis of regions flanking the B. pseudomallei penA gene revealed a putative regulator gene located downstream of penA. We have cloned and sequenced the penA gene from B. mallei and found it to be identical to penA from B. pseudomallei.
authors.affiliation: Department of Microbiology, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Chanwit
authors.initials: C
authors.lastname: Tribuddharat
authors.forename: Richard A
authors.initials: RA
authors.lastname: Moore
authors.forename: Patricia
authors.initials: P
authors.lastname: Baker
authors.forename: Donald E
authors.initials: DE
authors.lastname: Woods
mesh_terms: D024509:3' Flanking Region; D024506:5' Flanking Region; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016957:Burkholderia pseudomallei / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D002442:Ceftazidime / Q000494:pharmacology*; D019818:Clavulanic Acid / Q000494:pharmacology; D006801:Humans; D008554:Melioidosis / Q000188:drug therapy / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D019818:Clavulanic Acid; D002442:Ceftazidime; D001618:beta-Lactamases