AUTHOR=Marunga Joan , Goo Eunhye , Kang Yongsung , Hwang Ingyu 

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

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.721444

DOI=10.3389/fmicb.2021.721444

ISSN=1664-302X

ABSTRACT=<p>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 <italic>Burkholderia glumae</italic> 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 <italic>gluS</italic> or <italic>gluR</italic> conferred resistance to β-lactam antibiotics in <italic>B. glumae</italic>, whereas wild-type (WT) <italic>B. glumae</italic> was susceptible to these antibiotics. In <italic>gluS</italic> and <italic>gluR</italic> 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.</p>