TY  - JOUR
A1  - Fan, Sook-Ha
A1  - Ebner, Patrick
A1  - Reichert, Sebstian
A1  - Hertlein, Tobias
A1  - Zabel, Susanne
A1  - Lankapalli, Aditya Kumar
A1  - Nieselt, Kay
A1  - Ohlsen, Knut
A1  - Götz, Friedrich
T1  - MpsAB is important for Staphylococcus aureus virulence and growth at atmospheric CO2 levels
JF  - Nature Communications
N2  - The mechanisms behind carbon dioxide (CO2) dependency in non-autotrophic bacterial isolates are unclear. Here we show that the Staphylococcus aureus mpsAB operon, known to play a role in membrane potential generation, is crucial for growth at atmospheric CO2 levels. The genes mpsAB can complement an Escherichia coli carbonic anhydrase (CA) mutant, and CA from E. coli can complement the S. aureus delta-mpsABC mutant. In comparison with the wild type, S. aureus mps mutants produce less hemolytic toxin and are less virulent in animal models of infection. Homologs of mpsA and mpsB are widespread among bacteria and are often found adjacent to each other on the genome. We propose that MpsAB represents a dissolved inorganic carbon transporter, or bicarbonate concentrating system, possibly acting as a sodium bicarbonate cotransporter.
KW  - bacterial physiology
KW  - bacteriology
KW  - pathogens
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227624
VL  - 10
ER  - 
TY  - JOUR
A1  - Nguyen, Minh-Thu
A1  - Saising, Jongkon
A1  - Tribelli, Paula Maria
A1  - Nega, Mulugeta
A1  - Diene, Seydina M.
A1  - François, Patrice
A1  - Schrenzel, Jacques
A1  - Spröer, Cathrin
A1  - Bunk, Boyke
A1  - Ebner, Patrick
A1  - Hertlein, Tobias
A1  - Kumari, Nimerta
A1  - Härtner, Thomas
A1  - Wistuba, Dorothee
A1  - Voravuthikunchai, Supayang P.
A1  - Mäder, Ulrike
A1  - Ohlsen, Knut
A1  - Götz, Friedrich
T1  - Inactivation of farR Causes High Rhodomyrtone Resistance and Increased Pathogenicity in Staphylococcus aureus
JF  - Frontiers in Microbiology
N2  - 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 (RomR) 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 RomR clone. Particularly the upregulation of agr and sarA leads to increased expression of virulence genes rendering the RomR 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 RomR clone compared to its parental strain HG001. If farE is deleted in the RomR clone, or, if native farR is expressed in the RomR strain, the corresponding strains become hypersensitive to Rom. Overall, we show here that the high Rom-resistance is mediated by overexpression of farE in the RomR clone, that FarR is an important regulator, and that the point mutation in farR (RomR clone) makes the clone hyper-virulent.
KW  - antibiotic
KW  - Gram-positive bacteria
KW  - rhodomyrtone
KW  - Staphylococcus
KW  - membrane active
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224117
VL  - 10
ER  -