| Autor: |
Moxi Yu, Yachen Hou, Meiling Cheng, Yongshen Liu, Caise Ling, Dongshen Zhai, Hui Zhao, Yaoyao Li, Yamiao Chen, Xiaoyan Xue, Xue Ma, Min Jia, Bin Wang, Pingan Wang, Mingkai Li |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Antibiotics, Vol 11, Iss 11, p 1497 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2079-6382 |
| DOI: |
10.3390/antibiotics11111497 |
| Popis: |
Methicillin-resistant Staphylococcus aureus (MRSA)-caused infection is difficult to treat because of its resistance to commonly used antibiotic, and poses a significant threat to public health. To develop new anti-bacterial agents to combat MRSA-induced infections, we synthesized novel squaric amide derivatives and evaluated their anti-bacterial activity by determining the minimum inhibitory concentration (MIC). Additionally, inhibitory activity of squaric amide 2 (SA2) was measured using the growth curve assay, time-kill assay, and an MRSA-induced skin infection animal model. A scanning electron microscope and transmission electron microscope were utilized to observe the effect of SA2 on the morphologies of MRSA. Transcriptome analysis and real-time PCR were used to test the possible anti-bacterial mechanism of SA2. The results showed that SA2 exerted bactericidal activity against a number of MRSA strains with an MIC at 4–8 µg/mL. It also inhibited the bacterial growth curve of MRSA strains in a dose-dependent manner, and reduced the colony formation unit in 4× MIC within 4–8 h. The infective lesion size and the bacterial number in the MRSA-induced infection tissue of mice were reduced significantly within 7 days after SA2 treatment. Moreover, SA2 disrupted the bacterial membrane and alanine dehydrogenase-dependent NAD+/NADH homeostasis. Our data indicates that SA2 is a possible lead compound for the development of new anti-bacterial agents against MRSA infection. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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