Burkholderia pseudomallei class a beta-lactamase mutations that confer selective resistance against ceftazidime or clavulanic acid inhibition.
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.
Tribuddharat
Chanwit
C
Department of Microbiology, Mahidol University, Bangkok 10700, Thailand.
Moore
Richard A
RA
Baker
Patricia
P
Woods
Donald E
DE
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
D000900:Anti-Bacterial Agents; D019818:Clavulanic Acid; D002442:Ceftazidime; D001618:beta-Lactamases