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.