Hal will be stopped for maintenance from friday on june 10 at 4pm until monday june 13 at 9am. More information
Skip to Main content Skip to Navigation
Journal articles

Inactivation of farR Causes High Rhodomyrtone Resistance and Increased Pathogenicity in Staphylococcus aureus

Abstract : Rhodomyrtone (Rom) is an acylphloroglucinol antibiotic originally isolated from leaves of Rhodomyrtus tomentosa. Rom targets the bacterial membrane and is active against a wide range of Gram-positive bacteria but the exact mode of action remains obscure. Here we isolated and characterized a spontaneous Rom-resistant mutant from the model strain Staphylococcus aureus HG001 (Rom R) to learn more about the resistance mechanism. We showed that Rom-resistance is based on a single point mutation in the coding region of farR [regulator of fatty acid (FA) resistance] that causes an amino acid change from Cys to Arg at position 116 in FarR, that affects FarR activity. Comparative transcriptome analysis revealed that mutated farR affects transcription of many genes in distinct pathways. FarR represses for example the expression of its own gene (farR), its flanking gene farE (effector of FA resistance), and other global regulators such as agr and sarA. All these genes were consequently upregulated in the Rom R clone. Particularly the upregulation of agr and sarA leads to increased expression of virulence genes rendering the Rom R clone more cytotoxic and more pathogenic in a mouse infection model. The Rom-resistance is largely due to the de-repression of farE. FarE is described as an efflux pump for linoleic and arachidonic acids. We observed an increased release of lipids in the Rom R clone compared to its parental strain HG001. If farE is deleted in the Rom R clone, or, if native farR is expressed in the Rom R strain, Frontiers in Microbiology | www.frontiersin.org 1 May 2019 | Volume 10 | Article 1157 Nguyen et al. Rhodomyrtone (ROM) Resistance in S. aureus the corresponding strains become hypersensitive to Rom. Overall, we show here that the high Rom-resistance is mediated by overexpression of farE in the Rom R clone, that FarR is an important regulator, and that the point mutation in farR (Rom R clone) makes the clone hyper-virulent.
Complete list of metadata

Cited literature [52 references]  Display  Hide  Download

Contributor : Isabelle Combe Connect in order to contact the contributor
Submitted on : Thursday, November 21, 2019 - 2:50:04 PM
Last modification on : Wednesday, August 11, 2021 - 7:00:11 PM


Publication funded by an institution


Distributed under a Creative Commons Attribution 4.0 International License




Minh-Thu Nguyen, Jongkon Saising, Paula Maria Tribelli, Mulugeta Nega, Seydina Diene, et al.. Inactivation of farR Causes High Rhodomyrtone Resistance and Increased Pathogenicity in Staphylococcus aureus. Frontiers in Microbiology, Frontiers Media, 2019, 10, ⟨10.3389/fmicb.2019.01157⟩. ⟨hal-02263616⟩



Record views


Files downloads