title: Potential targets by pentacyclic triterpenoids from Callicarpa farinosa against methicillin-resistant and sensitive Staphylococcus aureus.
abstract: The evolution of antibiotic resistance in Staphylococcus aureus showed that there is no long-lasting remedy against this pathogen. The limited number of antibacterial classes and the common occurrence of cross-resistance within and between classes reinforce the urgent need to discover new compounds targeting novel cellular functions not yet targeted by currently used drugs. One of the experimental approaches used to discover novel antibacterials and their in vitro targets is natural product screening. Three known pentacyclic triterpenoids were isolated for the first time from the bark of Callicarpa farinosa Roxb. (Verbenaceae) and identified as α-amyrin [3β-hydroxy-urs-12-en-3-ol], betulinic acid [3β-hydroxy-20(29)-lupaene-28-oic acid], and betulinaldehyde [3β-hydroxy-20(29)-lupen-28-al]. These compounds exhibited antimicrobial activities against reference and clinical strains of methicillin-resistant (MRSA) and methicillin-sensitive S. aureus (MSSA), with minimum inhibitory concentration (MIC) ranging from 2 to 512 μg/mL. From the genome-wide transcriptomic analysis to elucidate the antimicrobial effects of these compounds, multiple novel cellular targets in cell division, two-component system, ABC transporters, fatty acid biosynthesis, peptidoglycan biosynthesis, aminoacyl-tRNA synthetases, ribosomes and β-lactam resistance pathways are affected, resulting in destabilization of the bacterial cell membrane, halt in protein synthesis, and inhibition of cell growth that eventually lead to cell death. The novel targets in these essential pathways could be further explored in the development of therapeutic compounds for the treatment of S. aureus infections and help mitigate resistance development due to target alterations.
authors: School of Medicine and Health Sciences, Monash University Sunway Campus, Bandar Sunway, Malaysia; International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia. Electronic address: pooiyin@hotmail.com.
authors: Pooi Yin
authors: PY
authors: Chung
authors: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: Lip Yong
authors: LY
authors: Chung
authors: School of Medicine and Health Sciences, Monash University Sunway Campus, Bandar Sunway, Malaysia.
authors: Parasakthi
authors: P
authors: Navaratnam
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D032408:Callicarpa / Q000737:chemistry*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D016106:Methicillin Resistance; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D053978:Pentacyclic Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics; D059467:Transcriptome; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000094062:Betulinic Acid
chemical_list: D000890:Anti-Infective Agents; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D014315:Triterpenes; D009828:Oleanolic Acid; C036380:beta-amyrin; D000094062:Betulinic Acid
keywords: Antimicrobial activity; Betulinaldehyde (Pubmed CID: 99615); Betulinic acid (Pubmed CID: 64971); Callicarpa farinosa; Mechanisms of action; Pentacyclic triterpenoids; Staphylococcus aureus; α-Amyrin (Pubmed CID: 225688)