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Antibacterial Peptide NP-6 Affects Staphylococcus aureus by Multiple Modes of Action.

ABSTRACT: Our previous study extracted and identified an antibacterial peptide that was named NP-6. Herein, we investigated the physicochemical properties of NP-6, and elucidated the mechanisms underlying its antimicrobial activity against Staphylococcus aureus. The results showed that the hemolysis activity of NP-6 was 2.39 ± 0.13%, lower than Nisin A (3.91 ± 0.43%) at the same concentration (512 µg/mL). Negligible cytotoxicity towards RAW264.7 cells was found when the concentration of NP-6 was lower than 512 µg/mL. In addition, it could keep most of its activity in fetal bovine serum. Moreover, transmission electron microscopy, confocal laser scanning microscopy, and flow cytometry results showed that NP-6 can destroy the integrity of the bacterial cell membrane and increase the membrane permeability. Meanwhile, NP-6 had binding activity with bacterial DNA and RNA in vitro and strongly inhibited the intracellular β-galactosidase activity of S. aureus. Our findings suggest that NP-6 could be a promising candidate against S. aureus.

SUBMITTER: Hou X

PROVIDER: S-EPMC9319634 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Antibacterial Peptide NP-6 Affects <i>Staphylococcus aureus</i> by Multiple Modes of Action.

Hou Xiaoyan X Li Jianlong J Tang Huaqiao H Li Qingye Q Shen Guanghui G Li Shanshan S Chen Anjun A Peng Zixin Z Zhang Yu Y Li Chaowei C Zhang Zhiqing Z

International journal of molecular sciences 20220715 14

Our previous study extracted and identified an antibacterial peptide that was named NP-6. Herein, we investigated the physicochemical properties of NP-6, and elucidated the mechanisms underlying its antimicrobial activity against <i>Staphylococcus aureus</i>. The results showed that the hemolysis activity of NP-6 was 2.39 ± 0.13%, lower than Nisin A (3.91 ± 0.43%) at the same concentration (512 µg/mL). Negligible cytotoxicity towards RAW264.7 cells was found when the concentration of NP-6 was lo ...[more]

PMID: 35887160

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Project description: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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Antibacterial Peptide NP-6 Affects Staphylococcus aureus by Multiple Modes of Action.

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Antibacterial Peptide NP-6 Affects <i>Staphylococcus aureus</i> by Multiple Modes of Action.

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