Rhodomyrtone (Rom) is a membrane-active compound

Abstract

Particularly in Asia medicinal plants with antimicrobial activity are used for therapeutic purpose. One such plant-derived antibiotic is rhodomyrtone (Rom) isolated from Rhodomyrtus tomentosa leaves. Rom shows high antibacterial activity against a wide range of Gram-positive bacteria, however, its mode of action is still unclear. Reporter gene assays and proteomic profiling experiments in Bacillus subtilis indicate that Rom does not address classical antibiotic targets like translation, transcription or DNA replication, but acts at the cytoplasmic membrane. 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 pore-formation as for example nisin. Lipid staining revealed that Rom induces local membrane damage. Rom's antimicrobial activity can be antagonized in the presence of a very narrow spectrum of saturated fatty acids (C15:0, C16:0, or C18:0) that most likely contribute to counteract the membrane damage. Gram-negative bacteria are resistant to Rom, presumably due to reduced penetration through the outer membrane and its neutralization by LPS. Rom is cytotoxic for many eukaryotic cells and studies with human erythrocytes showed that Rom induces eryptosis accompanied by erythrocyte shrinkage, cell membrane blebbing, and membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Rom's distinctive interaction with the cytoplasmic membrane reminds on the amphipathic, alpha-helical peptides, the phenol-soluble modulins (PSMs), and renders Rom an important tool for the investigation of membrane physiology.

Interspecies Comparison of the Bacterial Response to Allicin Reveals Species‐Specific Defense Strategies

“…To identify commonalities of the physiological impact of allicin to that of other antibacterial agents, we compared the proteomic response to allicin to a response library containing 44 proteomic responses of B. subtilis to known antimicrobial agents . Regarding the number of induced proteins, with 56 marker proteins, allicin evoked the most complex response in B. subtilis among the tested compounds.…”

Antibacterial mechanism of rhodomyrtone involves the disruption of nucleoid segregation checkpoint in Streptococcus suis

“…These indicated that the compound disturbed the intracellular bacterial protein homeostasis. Furthermore, Saeloh et al (2018) demonstrated that rhodomyrtone caused delocalization of membrane proteins correlated to the cell size and shape defects in B. subtilis and S. aureus (Saising et al 2018;Sianglum et al 2018). Two important cell division proteins, DivIVA and FtsA were known to associate with FtsZ during the septum formation as a final step of cell division.…”

“…More recently, rhodomyrtone was clearly demonstrated to be a membrane-active compound. Following the treatment, S. aureus membrane potential decrease immediately at low doses resulted in releasing of ATP and cytoplasmic protein without pore-formation effect (Saising et al 2018). Other workers demonstrated the increase in membrane fluidity and the collapsed membrane potential in Bacillus subtilis as well as the relocalization of seven membrane proteins (FtsA, DivIVA, MinD, PlsX, MreB, MurG and SdhA), trapping within the region of increased lipid fluidity (RIF) (Saeloh et al 2018).…”

Antibacterial mechanism of rhodomyrtone involves the disruption of nucleoid segregation checkpoint in Streptococcus suis

“…Furthermore, Saeloh et al (2018) demonstrated that rhodomyrtone caused delocalization of membrane proteins correlated to the cell size and shape defects in B. subtilis and S. aureus (Saising et al 2018;Sianglum et al 2018). Two important cell division proteins, DivIVA and FtsA were known to associate with FtsZ during the septum formation as a nal step of cell division.…”

“…More recently, rhodomyrtone was clearly demonstrated to be a membrane-active compound. Following the treatment, S. aureus membrane potential decrease immediately at low doses resulted in releasing of ATP and cytoplasmic protein without pore-formation effect (Saising et al 2018). Other workers demonstrated the increase in membrane uidity and the collapsed membrane potential in Bacillus subtilis as well as the relocalization of seven membrane proteins (FtsA, DivIVA, MinD, PlsX, MreB, MurG and SdhA), trapping within the region of increased lipid uidity (RIF) (Saeloh et al 2018).…”