Rhodomyrtone (Rom) is a broad-spectrum antibiotic active against many Gram-positive pathogens. It belongs to the substance class of acylphloroglucinols and can be chemically synthesized. In
Staphylococcus aureus, Rom decreases the membrane potential within seconds and at low doses, causes release of ATP and even the excretion of cytoplasmic proteins (ECP), but does not induce poreformation as for example nisin. Lipid staining revealed that Rom induces local membrane damage. Rom’s antimicrobial activity can be antagonized by certain fatty acids. Highly Rom-resistant mutants (RomR) occur with low frequency. They revealed only one point mutation in farR (regulator of fatty acid resistance) causing an amino acid change from Cys to Arg in FarR*. FarR* FarR* was not inactivated but mutated to a strong activator of divergently transcribed farE (fatty acid efflux pump). Mainly the upregulation of the fatty acid efflux pump FarE causes RomR phenotype as farE deletion in either the parent or the RomR strain (RomRΔfarE) became hypersensitive to Rom. Comparative lipidome and P-lipidome analysis of the supernatant (exo-lipidomics) and the pellet fraction revealed that the RomR strain excreted about ten times more phosphatidyl glycerols (PGs) than the parent strain or the ΔfarE mutants. Since the PG content in the supernatant (2244 ng/OD) was more than 100-fold higher than that of fatty acids (FAs), we assumed that FarE is rather a PG-efflux pump, and that PG interacts with Rom thereby abrogating its antimicrobial activity. Indeed, by static and dynamic light scattering (SLS/ DLS) and isothermal titration calorimetry (ITC) analyses we could demonstrate that both PG and Rom were vesicular and reacted with each other in milli-seconds to form a 1:1.49 (Rom:PG32:0) complex. The binding is entropic-driven and hence hydrophobic and low-specific in nature. Our results indicate that the cytoplasmic membrane is the actual target of Rom which is also in agreement with Rom’s induced rapid collapse of the membrane potential and decreased membrane integrity. Antibiotics that interact with PG are rare. Since Rom can be chemically synthesized, it serves as a lead compound for synthesis of improved variants.
United Scientific Group (A non-profit organization) warmly welcome you to the Virtual One-day Conference on Staphylococcal Infections (STAPH-2022) scheduled for Tuesday, May 10, 2022
STAPH-2022 will cover interdisciplinary latest research findings regards to Staphylococcus aureus and Staphylococcal Infections. This conference will strive hard to create a platform of collaborations and meetings where all the investigators, clinicians, industry experts and young researchers will meet at one place to share and gain knowledge through discussions and basic scientists who study pathogenesis of infection and the biology of Staphylococcus.
This virtual conference will provide an ideal, cost-effective format with as it offers:
In this regard, we warmly welcome you to join us for one-day which includes thought-provoking presentations and discussions. We hope that you will enjoy this conference and benefit from networking with attendees and speakers.
- (1) Cost-Saving – Engage without the expense and hassle of travel, hotel bookings, and spend your funds on Technology.
- (2) Convenience – Attend from your home or work, without risk of travel during the COVID-19 pandemic.
- (3) Focused presentations - On the latest in Staphylococcal infections typically before publication.
- (4) Great Speakers - Experience powerful education, learning, innovation by internationally recognized speakers.
- (5) Connects with Internationally Renowned Researchers from all over the globe to network.