ArticleBMC microbiology2022
Antibacterial activities and action mode of anti-hyperlipidemic lomitapide against Staphylococcus aureus.
Article in BMC microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Network-based bioinformatics for the prediction of candidate SNPs in Staphylococcus aureus virulence and resistance genes.Folia microbiologica · 2026Article
- Repurposing Azeliragon as a novel antibacterial agent against methicillin-resistant Staphylococcus aureus via combined membrane phospholipids and cell wall targeting.Communications biology · 2026Article
- Antimicrobial and synergistic effects of lemongrass and geranium essential oils againstWorld journal of critical care medicine · 2024Article
- Review
- Antibacterial activity and mechanisms of D-3263 against Staphylococcus aureus.BMC microbiology · 2024Article
- Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistantFrontiers in microbiology · 2024Article
- Antibacterial and Antibiofilm Activities of Sertindole and Its Antibacterial Mechanism againstACS omega · 2023Article
- Battle royale: Immune response on biofilms - host-pathogen interactions.Current research in immunology · 2023Review
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Authors and funding
11 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe increasing emergence of multidrug-resistant Gram-positive bacterial infections necessitates new antibacterial agents with novel mechanisms of action that can be used to treat these infections. Lomitapide has been approved by FDA for years in reducing levels of low-density lipoprotein (LDL) in cases of familial hypercholesterolemia, whereas the antibacterial effect of lomitapide remains elusive. In this study, the inhibitory activities of lomitapide against Gram-positive bacteria were the first time explored. Quantitative proteomics analysis was then applied to investigate the mechanisms of action of lomitapide.
resultsThe minimum inhibitory concentration (MIC) values of lomitapide against Gram-positive bacteria including both methicillin sensitive and resistant Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, and Streptococcus agalactiae were range 12.5-50 μM. Moreover, lomitapide also inhibited anti-biofilm activity against clinical S. aureus isolates. A total of 106 proteins with > 1.5-fold changes in expression were identified upon 1/2 × MIC lomitapide exposure, including 83 up-regulated proteins and 23 down-regulated proteins. Based on bioinformatics analysis, the expression of cell wall damage response proteins including two-component system VraS/VraR, lipoteichoic acid (LPA) D-alanylnation related proteins D-alanyl carrier protein (dltC) and carrier protein ligase (dltA), methionine sulfoxide reductases (mrsA1 and mrsB) were up-regulated. Moreover, the expression of SaeS and multiple fibrinogen-binding proteins (SAOUHSC_01110, FnBPB, SAOUHSC_02802, SdrC, SdrD) which were involved in the bacterial adhesion and biofilm formation, was inhibited by lomitapide. Furthermore, VraS/VraR deletion mutant (ΔvraSR) showed an enhanced lomitapide sensitivity phenotype.
conclusionLomitapide displayed broad antimicrobial activities against Gram-positive bacteria. The antibacterial effect of lomitapide may be caused by cell wall destruction, while the anti-biofilm activity may be related to the inhibition of surface proteins.
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