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Mutations in the Two-Component GluS-GluR Regulatory System Confer Resistance to β-Lactam Antibiotics in Burkholderia glumae

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Title: Mutations in the Two-Component GluS-GluR Regulatory System Confer Resistance to β-Lactam Antibiotics in Burkholderia glumae
Authors: Joan Marunga, Eunhye Goo, Yongsung Kang, Ingyu Hwang
Source: Frontiers in Microbiology, Vol 12 (2021)
Publisher Information: Frontiers Media S.A., 2021.
Publication Year: 2021
Collection: LCC:Microbiology
Subject Terms: β-lactam resistance, β-lactamase, Burkholderia glumae, penicillin-binding protein, rice panicle blight, two-component systems, Microbiology, QR1-502
More Details: Bacteria have specific signaling systems to overcome selective pressure, such as exposure to antibiotics. The two-component system (TCS) plays an important role in the development of antibiotic resistance. Using the rice pathogen Burkholderia glumae BGR1 as a model organism, we showed that the GluS (BGLU_1G13350) – GluR (BGLU_1G13360) TCS, consisting of a sensor kinase and response regulator, respectively, contributes to β-lactam resistance through a distinct mechanism. Inactivation of gluS or gluR conferred resistance to β-lactam antibiotics in B. glumae, whereas wild-type (WT) B. glumae was susceptible to these antibiotics. In gluS and gluR mutants, the expression of genes encoding metallo-β-lactamases (MBLs) and penicillin-binding proteins (PBPs) was significantly higher than in the WT. GluR-His bound to the putative promoter regions of annotated genes encoding MBL (BGLU_1G21360) and PBPs (BGLU_1G13280 and BGLU_1G04560), functioning as a repressor. These results demonstrate that the potential to attain β-lactam resistance may be genetically concealed in the TCS, in contrast to the widely accepted view of the role of TCS in antibiotic resistance. Our findings provide a new perspective on antibiotic resistance mechanisms, and suggest a different therapeutic approach for successful control of bacterial pathogens.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-302X
Relation: https://www.frontiersin.org/articles/10.3389/fmicb.2021.721444/full; https://doaj.org/toc/1664-302X
DOI: 10.3389/fmicb.2021.721444
Access URL: https://doaj.org/article/ed5192c1a6de419fb9932f6cf9ca119f
Accession Number: edsdoj.5192c1a6de419fb9932f6cf9ca119f
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  Data: Mutations in the Two-Component GluS-GluR Regulatory System Confer Resistance to β-Lactam Antibiotics in Burkholderia glumae
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  Data: <searchLink fieldCode="AR" term="%22Joan+Marunga%22">Joan Marunga</searchLink><br /><searchLink fieldCode="AR" term="%22Eunhye+Goo%22">Eunhye Goo</searchLink><br /><searchLink fieldCode="AR" term="%22Yongsung+Kang%22">Yongsung Kang</searchLink><br /><searchLink fieldCode="AR" term="%22Ingyu+Hwang%22">Ingyu Hwang</searchLink>
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  Data: Frontiers in Microbiology, Vol 12 (2021)
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  Data: Bacteria have specific signaling systems to overcome selective pressure, such as exposure to antibiotics. The two-component system (TCS) plays an important role in the development of antibiotic resistance. Using the rice pathogen Burkholderia glumae BGR1 as a model organism, we showed that the GluS (BGLU_1G13350) – GluR (BGLU_1G13360) TCS, consisting of a sensor kinase and response regulator, respectively, contributes to β-lactam resistance through a distinct mechanism. Inactivation of gluS or gluR conferred resistance to β-lactam antibiotics in B. glumae, whereas wild-type (WT) B. glumae was susceptible to these antibiotics. In gluS and gluR mutants, the expression of genes encoding metallo-β-lactamases (MBLs) and penicillin-binding proteins (PBPs) was significantly higher than in the WT. GluR-His bound to the putative promoter regions of annotated genes encoding MBL (BGLU_1G21360) and PBPs (BGLU_1G13280 and BGLU_1G04560), functioning as a repressor. These results demonstrate that the potential to attain β-lactam resistance may be genetically concealed in the TCS, in contrast to the widely accepted view of the role of TCS in antibiotic resistance. Our findings provide a new perspective on antibiotic resistance mechanisms, and suggest a different therapeutic approach for successful control of bacterial pathogens.
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      – Text: English
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      – SubjectFull: β-lactam resistance
        Type: general
      – SubjectFull: β-lactamase
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      – TitleFull: Mutations in the Two-Component GluS-GluR Regulatory System Confer Resistance to β-Lactam Antibiotics in Burkholderia glumae
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