ArcR contributes to tolerance to fluoroquinolone antibiotics by regulating katA in Staphylococcus aureus

Abstract

Staphylococcus aureus is an opportunistic pathogen that shows a unique ability to quickly respond to a variety of antibiotics. The Crp/Fnr family transcriptional regulator ArcR controls expression of arginine deiminase pathway genes arcABDC, which enable the utilization of arginine as an energy source for cell growth under anaerobic conditions. However, ArcR shares low overall similarity with other Crp/Fnr family proteins, suggesting that they differ in the response to environmental stress. In this study, MIC and survival assays were performed to determine the role of ArcR in antibiotic resistance and tolerance. The results showed that deletion of arcR reduced tolerance of S.aureus to fluoroquinolone antibiotics, mainly through a defect in the response to oxidative stress. In ΔarcR mutant, the expression of the major catalase gene katA was downregulated, and katA overexpression restored bacterial resistance to oxidative stress and antibiotics. We showed that ArcR directly regulated katA transcription by binding to the promoter region of katA. Therefore, our results revealed the contribution of ArcR in bacterial tolerance to oxidative stress and subsequently to fluoroquinolones antibiotics. This study added our understanding on the role of Crp/Fnr family in bacterial susceptibility to antibiotics.

D-Glucose-Mediated Gold Nanoparticle Fabrication for Colorimetric Detection of Foodborne Pathogens

“…The immunity evasion of S. aureus by opportunistic infections is a key characteristic closely associated with bacterial virulence and immune-modulating factors [ 13 ]. In particular, the catalase A gene ( katA ) of S. aureus modulates antibiotic resistance and oxidative stress [ 14 ]. Thus, S. aureus can easily adapt to other aerobic environments during infections owing to the high H 2 O 2 resistance of the katA gene [ 15 ].…”

Roles of the Crp/Fnr Family Regulator ArcR in the Hemolysis and Biofilm of Staphylococcus aureus

“…ArcR affected the utilization of arginine under anaerobic conditions through the regulation of the pathway genes arcABDC [ 32 ]. Our previous study showed that ArcR contributed to the tolerance of fluoroquinolone antibiotics in S. aureus [ 33 ]. In this study, we showed the function of ArcR in virulence and biofilm formation.…”