title: Proteome analyses of cellular proteins in methicillin-resistant Staphylococcus aureus treated with rhodomyrtone, a novel antibiotic candidate.
abstract: The ethanolic extract from Rhodomyrtus tomentosa leaf exhibited good antibacterial activities against both methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus ATCC 29213. Its minimal inhibitory concentration (MIC) values ranged from 31.25-62.5 µg/ml, and the minimal bactericidal concentration (MBC) was 250 µg/ml. Rhodomyrtone, an acylphloroglucinol derivative, was 62.5-125 times more potent at inhibiting the bacteria than the ethanolic extract, the MIC and MBC values were 0.5 µg/ml and 2 µg/ml, respectively. To provide insights into antibacterial mechanisms involved, the effects of rhodomyrtone on cellular protein expression of MRSA have been investigated using proteomic approaches. Proteome analyses revealed that rhodomyrtone at subinhibitory concentration (0.174 µg/ml) affected the expression of several major functional classes of whole cell proteins in MRSA. The identified proteins involve in cell wall biosynthesis and cell division, protein degradation, stress response and oxidative stress, cell surface antigen and virulence factor, and various metabolic pathways such as amino acid, carbohydrate, energy, lipid, and nucleotide metabolism. Transmission electron micrographs confirmed the effects of rhodomyrtone on morphological and ultrastructural alterations in the treated bacterial cells. Biological processes in cell wall biosynthesis and cell division were interrupted. Prominent changes including alterations in cell wall, abnormal septum formation, cellular disintegration, and cell lysis were observed. Unusual size and shape of staphylococcal cells were obviously noted in the treated MRSA. These pioneer findings on proteomic profiling and phenotypic features of rhodomyrtone-treated MRSA may resolve its antimicrobial mechanisms which could lead to the development of a new effective regimen for the treatment of MRSA infections.
authors.affiliation: Department of Microbiology and Natural Products Research Center, Faculty of Science, Prince of Songkla University, Songkla, Thailand.
authors.forename: Wipawadee
authors.initials: W
authors.lastname: Sianglum
authors.forename: Potjanee
authors.initials: P
authors.lastname: Srimanote
authors.forename: Wijit
authors.initials: W
authors.lastname: Wonglumsom
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Kittiniyom
authors.forename: Supayang P
authors.initials: SP
authors.lastname: Voravuthikunchai
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000502:physiology; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use; D000431:Ethanol / Q000737:chemistry / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D020543:Proteome / Q000032:analysis / Q000187:drug effects*; D013997:Time Factors; D037521:Virulence Factors / Q000032:analysis / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015507:Drugs, Investigational; D010936:Plant Extracts; D020543:Proteome; D037521:Virulence Factors; D044004:Xanthones; C541823:rhodomyrtone; D000431:Ethanol