Antimicrobial activity and synergy of antibiotics with two biphenyl compounds, protosappanins A and B from Sappan Lignum against methicillin-resistant Staphylococcus aureus strains.
OBJECTIVE
This study aims to investigate antimicrobial ingredients from Sappan Lignum and to evaluate their synergy on methicillin-resistant Staphylococcus aureus strains with antibiotics.


METHODS
Bioactivity-guided phytochemical procedures were used to screen the active compounds. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were assayed by broth microdilution. The synergy was evaluated through checkerboard microdilution and loss of viability assays.


RESULTS
Protosappanins A (PsA) and B (PsB) were identified from Sappan Lignum extracts. They showed active against both S. aureus and MRSA with MIC or MIC50 at 64 (PsA) and 128 (PsB) mg/L alone. When they were used in combination with antibiotics, they showed best synergy with amikacin and gentamicin with MIC50 (mg/L) of amikacin reduced more significantly from 32 to four (with PsA) and eight (with PsB), and the fractional inhibitory concentration index (FICI) ranged between 0.078 and 0.500 (FICI50  = 0.375). Moreover, the resistance of MRSA towards amikacin and gentamicin could be reversed by the Clinical and Laboratory Standards Institute criteria. The combined bactericidal mode could as well be synergy. PsA and PsB showed very low cytotoxicity in comparison with their promising activity against MRSA.


CONCLUSIONS
Protosappanins A and B showed both alone activities and resistance reversal effects of amikacin and gentamicin against MRSA, which warrant further investigations for potential combinatory therapy of MRSA infection.
Research Center for Natural Medicines, Kunming General Hospital of Chengdu Military Command, Kunming, China.
Guo-Ying
GY
Zuo
Research Center for Natural Medicines, Kunming General Hospital of Chengdu Military Command, Kunming, China.|School of Pharmacy, Guiyang Medical University, Guiyang, China.|Department of Basic, Xingtai Medical College, Xingtai, China.
Zong-Qi
ZQ
Han
School of Basic Medical Sciences, Yunnan Traditional Chinese Medical College, Kunming, China.
Jun
J
Han
School of Pharmacy, Guiyang Medical University, Guiyang, China.
Xiao-Yan
XY
Hao
Research Center for Natural Medicines, Kunming General Hospital of Chengdu Military Command, Kunming, China.
Hua-Shu
HS
Tang
Research Center for Natural Medicines, Kunming General Hospital of Chengdu Military Command, Kunming, China.
Gen-Chun
GC
Wang
D000583:Amikacin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D029911:Caesalpinia / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004357:Drug Synergism; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D035964:Oxocins / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010636:Phenols / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D035964:Oxocins; D010636:Phenols; C000603101:protosappanin B; C090723:protosappanin A; D000583:Amikacin
MRSA; Sappan Lignum; protosappanin; resistance reversal effect; synergy