Identification of novel amrR deletions as meropenem resistance mechanisms in clinical Burkholderia pseudomallei isolates
2
Issued Date
2025-05-01
Resource Type
eISSN
21650497
Scopus ID
2-s2.0-105004771071
Pubmed ID
40135925
Journal Title
Microbiology Spectrum
Volume
13
Issue
5
Rights Holder(s)
SCOPUS
Bibliographic Citation
Microbiology Spectrum Vol.13 No.5 (2025)
Suggested Citation
Nimnuan-Ngam S., Hii S.Y.F., Seng R., Saiprom N., Tandhavanant S., West T.E., Chantratita N. Identification of novel amrR deletions as meropenem resistance mechanisms in clinical Burkholderia pseudomallei isolates. Microbiology Spectrum Vol.13 No.5 (2025). doi:10.1128/spectrum.01936-24 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/110195
Title
Identification of novel amrR deletions as meropenem resistance mechanisms in clinical Burkholderia pseudomallei isolates
Corresponding Author(s)
Other Contributor(s)
Abstract
Burkholderia pseudomallei, an environmental bacterium, is the causative agent of melioidosis, a potentially fatal infectious disease predominantly found in tropical regions. Despite the bacterium’s intrinsic resistance to numerous antibiotics, the antibiotic resistance mechanisms remain poorly understood. Recently, we identified novel partial deletions in the amrR gene of meropenem less-susceptible (MEM-LS) isolates (DR10212A, DR90049A, and DR90031E) obtained from patients with melioidosis. In this study, we performed mutagenesis and quantitative reverse-transcription real-time polymerase chain reaction (RT-qPCR) to validate the roles of these partial deletions in the amrR gene in MEM-LS isolates. By introducing wild-type amrR fragments from strain K96243 into three parental MEM-LS isolates, we successfully constructed three complemented mutant strains (DR10212A∷K96243-amrR, DR90049A∷K96243-amrR, and DR90031E∷K96243-amrR), which exhibited significantly decreased MEM minimum inhibitory concentrations (MIC) compared with their parental strains. Consistent with the decreased MIC, the expression levels of AmrAB-OprA efflux pump genes (oprA, amrB, and amrA) in the complemented mutant strains were downregulated at least 5-fold compared with the parental isolates, indicating the significant role of the partial amrR gene deletions in MEM-LS. Our findings provide more understanding of the MEM resistance mechanisms of clinical isolates of B. pseudomallei, thereby enhancing future strategies for the treatment and management of melioidosis.