Synergism with Shikimic Acid Restores β-Lactam Antibiotic Activity against Methicillin-Resistant <i>Staphylococcus aureus</i>
Methicillin-resistant <i>Staphylococcus aureus</i> (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,...
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| Format: | Article |
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MDPI AG
2024-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/7/1528 |
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| author | Limin Hou Minqi Ye Xiaoyu Wang Yifan Zhu Xueyan Sun Ruiheng Gu Liangzhu Chen Binghu Fang |
| author_facet | Limin Hou Minqi Ye Xiaoyu Wang Yifan Zhu Xueyan Sun Ruiheng Gu Liangzhu Chen Binghu Fang |
| author_sort | Limin Hou |
| collection | DOAJ |
| description | Methicillin-resistant <i>Staphylococcus aureus</i> (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 <i>mec</i>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. |
| first_indexed | 2024-04-24T10:39:07Z |
| format | Article |
| id | doaj.art-6a6b7ce9a5464386bb45d6647762dd99 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-24T10:39:07Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-6a6b7ce9a5464386bb45d6647762dd992024-04-12T13:23:18ZengMDPI AGMolecules1420-30492024-03-01297152810.3390/molecules29071528Synergism with Shikimic Acid Restores β-Lactam Antibiotic Activity against Methicillin-Resistant <i>Staphylococcus aureus</i>Limin Hou0Minqi Ye1Xiaoyu Wang2Yifan Zhu3Xueyan Sun4Ruiheng Gu5Liangzhu Chen6Binghu Fang7College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, ChinaGuangdong Wenshi Dahuanong Biotechnology Co., Ltd., Yunfu 510610, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, ChinaMethicillin-resistant <i>Staphylococcus aureus</i> (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 <i>mec</i>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.https://www.mdpi.com/1420-3049/29/7/1528shikimic acidmethicillin-resistant <i>Staphylococcus aureus</i>synergistic effect |
| spellingShingle | Limin Hou Minqi Ye Xiaoyu Wang Yifan Zhu Xueyan Sun Ruiheng Gu Liangzhu Chen Binghu Fang Synergism with Shikimic Acid Restores β-Lactam Antibiotic Activity against Methicillin-Resistant <i>Staphylococcus aureus</i> Molecules shikimic acid methicillin-resistant <i>Staphylococcus aureus</i> synergistic effect |
| title | Synergism with Shikimic Acid Restores β-Lactam Antibiotic Activity against Methicillin-Resistant <i>Staphylococcus aureus</i> |
| title_full | Synergism with Shikimic Acid Restores β-Lactam Antibiotic Activity against Methicillin-Resistant <i>Staphylococcus aureus</i> |
| title_fullStr | Synergism with Shikimic Acid Restores β-Lactam Antibiotic Activity against Methicillin-Resistant <i>Staphylococcus aureus</i> |
| title_full_unstemmed | Synergism with Shikimic Acid Restores β-Lactam Antibiotic Activity against Methicillin-Resistant <i>Staphylococcus aureus</i> |
| title_short | Synergism with Shikimic Acid Restores β-Lactam Antibiotic Activity against Methicillin-Resistant <i>Staphylococcus aureus</i> |
| title_sort | synergism with shikimic acid restores β lactam antibiotic activity against methicillin resistant i staphylococcus aureus i |
| topic | shikimic acid methicillin-resistant <i>Staphylococcus aureus</i> synergistic effect |
| url | https://www.mdpi.com/1420-3049/29/7/1528 |
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