title: Antibacterial and synergic effects of gallic acid-grafted-chitosan with β-lactams against methicillin-resistant Staphylococcus aureus (MRSA).
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) is spreading worldwide, emphasizing the need to search for new antibiotics. The anti-MRSA activities of gallic acid-grafted-chitosans (GA-g-chitosans) were investigated against 2 MRSA standards and 10 MRSA clinical isolates by determining the minimum inhibitory concentrations (MICs). GA-g-chitosan (I), which has the highest gallic acid content, exhibited the strongest anti-MRSA activities, with MICs of 32-64 μg/mL. A time-kill investigation revealed that GA-g-chitosan (I) exhibited a bactericidal effect at twice the MIC, also demonstrating good thermal and pH stability. Investigation of cell envelope integrity showed the release of intracellular components with an increasing absorbance value at 260 nm, indicating cell envelope damage caused by the GA-g-chitosan (I), which was further confirmed by transmission electron microscopy. When GA-g-chitosans were combined with β-lactams, including ampicillin and penicillin, synergistic effects were observed on the 2 standard MRSA strains and on the 10 clinical isolates, with fractional inhibitory indices ranging from 0.125 to 0.625. In the time-kill dynamic confirmation test, synergistic bactericidal effects were observed for the combinations of GA-g-chitosans with β-lactams, and over 4.0 log CFU/mL reductions were observed after 24 h when combination treatment was used. These results may prove GA-g-chitosans to be a potent agent when combined with ampicillin and penicillin for the elimination of MRSA.
authors.affiliation: a Marine Biodiversity Institute of Korea, Seocheon 325-902, Republic of Korea.
authors.forename: Dae-Sung
authors.initials: DS
authors.lastname: Lee
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Eom
authors.forename: Young-Mog
authors.initials: YM
authors.lastname: Kim
authors.forename: Hye Seon
authors.initials: HS
authors.lastname: Kim
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Yim
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Do-Hyung
authors.initials: DH
authors.lastname: Kim
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Je
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry* / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004355:Drug Stability; D004357:Drug Synergism; D005707:Gallic Acid / Q000737:chemistry* / Q000494:pharmacology*; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D005707:Gallic Acid; D048271:Chitosan
keywords: MRSA; SARM; activité antibactérienne; antibacterial activity; cell envelope; chitosan; chitosane; effet synergique; enveloppe cellulaire; synergy effect