Bioassay-Guided Isolation of Antimicrobial Components and LC/QToF Profile of Plumeria obtusa: Potential for the Treatment of Antimicrobial Resistance.

The methanolic fraction (M-F) of the total extract (TE) of Plumeria obtusa L. aerial parts showed promising antibacterial effects against the MDR (multidrug-resistant) gram-negative pathogens Klebsiella pneumoniae and Escherichia coli O157:H7 [Shiga toxin-producing E. coli (STEC)]. In addition, M-F had a synergistic effect (in combination with vancomycin) against the MDR gram-positive strains MRSA (methicillin-resistant Staphylococcus aureus) and Bacillus cereus. After treating the K. pneumoniae- and STEC-infected mice with M-F (25 mg/kg, i.p.), the level of IgM and TNF-α was decreased and the severity of pathological lesions were reduced better than that observed after administration of gentamycin (33 mg/kg, i.p.). Thirty-seven compounds including 10 plumeria-type iridoids and 18 phenolics, 7 quinoline derivatives, 1 amino acid, and 1 fatty acid were identified in TE using LC/ESI-QToF. Furthermore, five compounds; kaempferol 3-O-rutinoside (M1), quercetin 3-O-rutinoside (M2), glochiflavanoside B (M3), plumieride (M4), and 13-O-caffeoylplumieride (M5) were isolated from M-F. M5 was active against K. pneumoniae (MIC of 64 μg/mL) and STEC (MIC of 32 μg/mL). These findings suggested that M-F and M5 are promising antimicrobial natural products for combating MDR K. pneumoniae and STEC nosocomial infections.