AI Article Synopsis
- The study explores the use of Caspofungin acetate (CAS) as an antibiotic adjuvant to enhance the effectiveness of existing antibiotics against Gram-negative bacteria (GNB), which are known for their resistance to treatments.
- CAS was identified from a large screening of FDA-approved drugs, showing the ability to boost the activity of rifampin and colistin against various GNB strains, even in multidrug-resistant cases.
- The research highlights that CAS works by disrupting the bacterial cell envelope and inhibiting biofilm formation, with PgaC identified as its target, suggesting a promising approach to tackle antimicrobial resistance.
Article Abstract
Introduction: Developing antibiotic adjuvants is an effective strategy to combat antimicrobial resistance (AMR). The envelope of Gram-negative bacteria (GNB) is a barrier to prevent the entry of antibiotics, making it an attractive target for novel antibiotic and adjuvant development.
Methods And Results: In this study, we identified Caspofungin acetate (CAS) as an antibiotic adjuvant against GNB in the repurposing screen of 3,158 FDA-approved drugs. Checkerboard assays suggested that CAS could enhance the antimicrobial activity of rifampin or colistin against various GNB strains , Moreover, larvae infection model also indicated that CAS significantly potentiated the efficacy of rifampin against multidrug-resistant 72 strain . Most importantly, resistance development assay showed that CAS was less susceptible to accelerating the resistance development of drug-sensitive strain MG1655. Functional studies and RNA-seq analysis confirmed that the mechanisms by which CAS enhanced the antimicrobial activities of antibiotics were involved in permeabilizing the bacterial cell envelope, disrupting proton motive force and inhibiting bacterial biofilm formation. Additionally, it has been found that PgaC is the CAS target and enzymatic assay has confirmed the inhibition activity.
Discussion: Our results illustrate the feasibility of CAS as an antibiotic adjuvant against GNB, which is an alternative strategy of anti-infection.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358092 | PMC |
| http://dx.doi.org/10.3389/fmicb.2024.1447485 | DOI Listing |
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