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Molecules (Basel, Switzerland)
Mar 29, 2024;29 (7):

Synergism with Shikimic Acid Restores β-Lactam Antibiotic Activity against Methicillin-Resistant .

Limin Hou, Minqi Ye, Xiaoyu Wang, Yifan Zhu, Xueyan Sun, Ruiheng Gu, Liangzhu Chen, Binghu Fang
Author Information
  1. Limin Hou: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
  2. Minqi Ye: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
  3. Xiaoyu Wang: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
  4. Yifan Zhu: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
  5. Xueyan Sun: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
  6. Ruiheng Gu: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
  7. Liangzhu Chen: Guangdong Wenshi Dahuanong Biotechnology Co., Ltd., Yunfu 510610, China.
  8. Binghu Fang: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
PMID: 38611807 DOI: 10.3390/molecules29071528

Abstract

Methicillin-resistant (MRSA) has evolved into a dangerous pathogen resistant to beta-lactam antibiotics (BLAs) and has become a worrisome superbug. In this study, a strategy in which shikimic acid (SA), which has anti-inflammatory and antibacterial activity, is combined with BLAs to restart BLA activity was proposed for MRSA treatment. The synergistic effects of oxacillin combined with SA against oxacillin resistance in vitro and in vivo were investigated. The excellent synergistic effect of the oxacillin and SA combination was confirmed by performing the checkerboard assay, time-killing assay, live/dead bacterial cell viability assay, and assessing protein leakage. SEM showed that the cells in the control group had a regular, smooth, and intact surface. In contrast, oxacillin and SA or the combination treatment group exhibited different degrees of surface collapse. q-PCR indicated that the combination treatment group significantly inhibited the expression of the A gene. In vivo, we showed that the combination treatment increased the survival rate and decreased the bacterial load in mice. These results suggest that the combination of oxacillin with SA is considered an effective treatment option for MRSA, and the combination of SA with oxacillin in the treatment of MRSA is a novel strategy.

Keywords

methicillin-resistant Staphylococcus aureus shikimic acid synergistic effect

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Grants

  1. 2019BT02N054/National Natural Science Foundation of China

MeSH Term

Animals
Mice
Methicillin-Resistant Staphylococcus aureus
Shikimic Acid
Monobactams
beta Lactam Antibiotics
Oxacillin

Chemicals

Shikimic Acid
Monobactams
beta Lactam Antibiotics
Oxacillin
Journal Article

Word Cloud

Created with Highcharts 10.0.0SAtreatmentoxacillincombinationMRSAsynergisticassaygroupBLAsstrategyshikimicacidactivitycombinedvivoeffectbacterialshowedsurfaceMethicillin-resistantevolveddangerouspathogenresistantbeta-lactamantibioticsbecomeworrisomesuperbugstudyanti-inflammatoryantibacterialrestartBLAproposedeffectsresistancevitroinvestigatedexcellentconfirmedperformingcheckerboardtime-killinglive/deadcellviabilityassessingproteinleakageSEMcellscontrolregularsmoothintactcontrastexhibiteddifferentdegreescollapseq-PCRindicatedsignificantlyinhibitedexpressiongeneincreasedsurvivalratedecreasedloadmiceresultssuggestconsideredeffectiveoptionnovelSynergismShikimicAcidRestoresβ-LactamAntibioticActivityMethicillin-Resistantmethicillin-resistantStaphylococcusaureus

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