Bactericidal and biofilm eradication efficacy of a fluorinated benzimidazole derivative, TFBZ, against methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus (MRSA) is a major inducement of nosocomial infections and its biofilm formation render the high tolerance to conventional antibiotics, which highlights the requirement to develop new antimicrobial agents urgently. In this study, we identified a fluorinated...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-04-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1342821/full |
| _version_ | 1797215850892099584 |
|---|---|
| author | Qian Chen Zhihui Dong Xuedi Yao Huan Sun Xin Pan Jikai Liu Rong Huang |
| author_facet | Qian Chen Zhihui Dong Xuedi Yao Huan Sun Xin Pan Jikai Liu Rong Huang |
| author_sort | Qian Chen |
| collection | DOAJ |
| description | Methicillin-resistant Staphylococcus aureus (MRSA) is a major inducement of nosocomial infections and its biofilm formation render the high tolerance to conventional antibiotics, which highlights the requirement to develop new antimicrobial agents urgently. In this study, we identified a fluorinated benzimidazole derivative, TFBZ, with potent antibacterial efficacy toward planktonic MRSA (MIC = 4 μg/mL, MBC = 8 μg/mL) and its persistent biofilms (≥99%, MBEC = 8 μg/mL). TFBZ manifested significant irreversible time-dependent killing against MRSA as characterized by diminished cell viability, bacterial morphological change and protein leakage. Furthermore, the results from CBD devices, crystal violet assay in conjunction with live/dead staining and scanning electron microscopy confirmed that TFBZ was capable of eradicating preformed MRSA biofilms with high efficiency. Simultaneously, TFBZ reduced the bacterial invasiveness and exerted negligible hemolysis and cytotoxicity toward mammalian cells, which ensuring the robust therapeutic effect on mouse skin abscess model. The transcriptome profiling and quantitative RT-PCR revealed that a set of encoding genes associated with cell adhesion, biofilm formation, translation process, cell wall biosynthesis was consistently downregulated in MRSA biofilms upon exposure to TFBZ. In conclusion, TFBZ holds promise as a valuable candidate for therapeutic applications against MRSA chronic infections. |
| first_indexed | 2024-04-24T11:36:38Z |
| format | Article |
| id | doaj.art-c56bae228f6541eebb5a429df93c11d6 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-24T11:36:38Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-c56bae228f6541eebb5a429df93c11d62024-04-10T04:59:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-04-011510.3389/fphar.2024.13428211342821Bactericidal and biofilm eradication efficacy of a fluorinated benzimidazole derivative, TFBZ, against methicillin-resistant Staphylococcus aureusQian Chen0Zhihui Dong1Xuedi Yao2Huan Sun3Xin Pan4Jikai Liu5Rong Huang6The Modernization Engineering Technology Research Center of Ethnic Minority Medicine of Hubei Province, School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, ChinaThe Modernization Engineering Technology Research Center of Ethnic Minority Medicine of Hubei Province, School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, ChinaThe Modernization Engineering Technology Research Center of Ethnic Minority Medicine of Hubei Province, School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, ChinaThe Modernization Engineering Technology Research Center of Ethnic Minority Medicine of Hubei Province, School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, ChinaInternational Cooperation Base for Active Substances in Traditional Chinese Medicine in Hubei Province, School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, ChinaThe Modernization Engineering Technology Research Center of Ethnic Minority Medicine of Hubei Province, School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, ChinaThe Modernization Engineering Technology Research Center of Ethnic Minority Medicine of Hubei Province, School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, ChinaMethicillin-resistant Staphylococcus aureus (MRSA) is a major inducement of nosocomial infections and its biofilm formation render the high tolerance to conventional antibiotics, which highlights the requirement to develop new antimicrobial agents urgently. In this study, we identified a fluorinated benzimidazole derivative, TFBZ, with potent antibacterial efficacy toward planktonic MRSA (MIC = 4 μg/mL, MBC = 8 μg/mL) and its persistent biofilms (≥99%, MBEC = 8 μg/mL). TFBZ manifested significant irreversible time-dependent killing against MRSA as characterized by diminished cell viability, bacterial morphological change and protein leakage. Furthermore, the results from CBD devices, crystal violet assay in conjunction with live/dead staining and scanning electron microscopy confirmed that TFBZ was capable of eradicating preformed MRSA biofilms with high efficiency. Simultaneously, TFBZ reduced the bacterial invasiveness and exerted negligible hemolysis and cytotoxicity toward mammalian cells, which ensuring the robust therapeutic effect on mouse skin abscess model. The transcriptome profiling and quantitative RT-PCR revealed that a set of encoding genes associated with cell adhesion, biofilm formation, translation process, cell wall biosynthesis was consistently downregulated in MRSA biofilms upon exposure to TFBZ. In conclusion, TFBZ holds promise as a valuable candidate for therapeutic applications against MRSA chronic infections.https://www.frontiersin.org/articles/10.3389/fphar.2024.1342821/fullmethicillin-resistant Staphylococcus aureusbiofilmsbenzimidazole derivativeantibacterialbiofilm eradication |
| spellingShingle | Qian Chen Zhihui Dong Xuedi Yao Huan Sun Xin Pan Jikai Liu Rong Huang Bactericidal and biofilm eradication efficacy of a fluorinated benzimidazole derivative, TFBZ, against methicillin-resistant Staphylococcus aureus Frontiers in Pharmacology methicillin-resistant Staphylococcus aureus biofilms benzimidazole derivative antibacterial biofilm eradication |
| title | Bactericidal and biofilm eradication efficacy of a fluorinated benzimidazole derivative, TFBZ, against methicillin-resistant Staphylococcus aureus |
| title_full | Bactericidal and biofilm eradication efficacy of a fluorinated benzimidazole derivative, TFBZ, against methicillin-resistant Staphylococcus aureus |
| title_fullStr | Bactericidal and biofilm eradication efficacy of a fluorinated benzimidazole derivative, TFBZ, against methicillin-resistant Staphylococcus aureus |
| title_full_unstemmed | Bactericidal and biofilm eradication efficacy of a fluorinated benzimidazole derivative, TFBZ, against methicillin-resistant Staphylococcus aureus |
| title_short | Bactericidal and biofilm eradication efficacy of a fluorinated benzimidazole derivative, TFBZ, against methicillin-resistant Staphylococcus aureus |
| title_sort | bactericidal and biofilm eradication efficacy of a fluorinated benzimidazole derivative tfbz against methicillin resistant staphylococcus aureus |
| topic | methicillin-resistant Staphylococcus aureus biofilms benzimidazole derivative antibacterial biofilm eradication |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1342821/full |
| work_keys_str_mv | AT qianchen bactericidalandbiofilmeradicationefficacyofafluorinatedbenzimidazolederivativetfbzagainstmethicillinresistantstaphylococcusaureus AT zhihuidong bactericidalandbiofilmeradicationefficacyofafluorinatedbenzimidazolederivativetfbzagainstmethicillinresistantstaphylococcusaureus AT xuediyao bactericidalandbiofilmeradicationefficacyofafluorinatedbenzimidazolederivativetfbzagainstmethicillinresistantstaphylococcusaureus AT huansun bactericidalandbiofilmeradicationefficacyofafluorinatedbenzimidazolederivativetfbzagainstmethicillinresistantstaphylococcusaureus AT xinpan bactericidalandbiofilmeradicationefficacyofafluorinatedbenzimidazolederivativetfbzagainstmethicillinresistantstaphylococcusaureus AT jikailiu bactericidalandbiofilmeradicationefficacyofafluorinatedbenzimidazolederivativetfbzagainstmethicillinresistantstaphylococcusaureus AT ronghuang bactericidalandbiofilmeradicationefficacyofafluorinatedbenzimidazolederivativetfbzagainstmethicillinresistantstaphylococcusaureus |