Federica Dell’Annunziata, Veronica Folliero, Roberta Della Marca, Francesca Palma, Giuseppina Sanna, Anna De Filippis, Pasquale Pagliano, Aldo Manzin, Gianluigi Franci, Massimiliano Galdiero
{"title":"重新利用替尼泊苷对革兰氏阳性菌的抗菌活性","authors":"Federica Dell’Annunziata, Veronica Folliero, Roberta Della Marca, Francesca Palma, Giuseppina Sanna, Anna De Filippis, Pasquale Pagliano, Aldo Manzin, Gianluigi Franci, Massimiliano Galdiero","doi":"10.1155/2024/9389729","DOIUrl":null,"url":null,"abstract":"<p>Drug repurposing is sparking considerable interest due to reduced costs and development times. The current study details the screening of teniposide, an antitumor drug, for its antibacterial activity against both Gram-positive and Gram-negative strains, with a focus on <i>Staphylococcus epidermidis</i> (<i>S. epidermidis</i>), the primary causative agent of nosocomial and transplant-related infections. The cytotoxicity was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and hemolysis assays on immortalized human keratinocyte (HaCaT) cells and human erythrocytes. After 20 h of treatment, the recorded concentrations causing 50% cytotoxicity (CC<sub>50</sub>) and hemolysis (HC<sub>50</sub>) were 33.63 and 121.55 <i>μ</i>g/mL, respectively. The antibacterial screening employed disk diffusion, the broth microdilution method, LIVE/DEAD staining, and a time-killing test. The drug induced a growth inhibitory area in the 22–25 mm range for all Gram-positive strains. The minimum concentration that inhibited 90% of bacteria (MIC<sub>90</sub>) was 6.25 <i>μ</i>g/mL against <i>Staphylococcus aureus</i> and <i>S. epidermidis</i> and 12.5 <i>μ</i>g/mL versus <i>Enterococcus faecalis</i>, exhibiting bactericidal action. Treatment resulted in <i>S. epidermidis</i> cell morphology deformities and damage to the cell membrane, observed by scanning electron microscopy (SEM). Mechanism analysis revealed alterations in the selective permeability of the cell membrane, observed under the fluorescence microscope by the absorption of propidium iodide (PI). The synergistic effect of teniposide in combination with fosfomycin and gentamicin was documented by disk diffusion and checkboard assay, recording a fractional inhibitory concentration index (FICI) of 0.28 and 0.37, respectively. The drug’s action on <i>S. epidermidis</i> biofilm biomass was investigated using crystal violet (CV) and MTT. Teniposide affected biofilm viability in a dose-dependent manner, inducing, at a concentration of 3.12 <i>μ</i>g/mL, a matrix inhibition of about 42% and 61%, with a sessile metabolic activity of 54% and 24% recorded after 2 and 24 h, respectively. Overall, this study suggests the potential repurposing of the anticancer drug teniposide as a therapeutic agent to counteract <i>S. epidermidis</i> infections.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2024 1","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/9389729","citationCount":"0","resultStr":"{\"title\":\"Repurposing the Antibacterial Activity of the Drug Teniposide Against Gram-Positive Bacteria\",\"authors\":\"Federica Dell’Annunziata, Veronica Folliero, Roberta Della Marca, Francesca Palma, Giuseppina Sanna, Anna De Filippis, Pasquale Pagliano, Aldo Manzin, Gianluigi Franci, Massimiliano Galdiero\",\"doi\":\"10.1155/2024/9389729\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Drug repurposing is sparking considerable interest due to reduced costs and development times. The current study details the screening of teniposide, an antitumor drug, for its antibacterial activity against both Gram-positive and Gram-negative strains, with a focus on <i>Staphylococcus epidermidis</i> (<i>S. epidermidis</i>), the primary causative agent of nosocomial and transplant-related infections. The cytotoxicity was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and hemolysis assays on immortalized human keratinocyte (HaCaT) cells and human erythrocytes. After 20 h of treatment, the recorded concentrations causing 50% cytotoxicity (CC<sub>50</sub>) and hemolysis (HC<sub>50</sub>) were 33.63 and 121.55 <i>μ</i>g/mL, respectively. The antibacterial screening employed disk diffusion, the broth microdilution method, LIVE/DEAD staining, and a time-killing test. The drug induced a growth inhibitory area in the 22–25 mm range for all Gram-positive strains. The minimum concentration that inhibited 90% of bacteria (MIC<sub>90</sub>) was 6.25 <i>μ</i>g/mL against <i>Staphylococcus aureus</i> and <i>S. epidermidis</i> and 12.5 <i>μ</i>g/mL versus <i>Enterococcus faecalis</i>, exhibiting bactericidal action. Treatment resulted in <i>S. epidermidis</i> cell morphology deformities and damage to the cell membrane, observed by scanning electron microscopy (SEM). Mechanism analysis revealed alterations in the selective permeability of the cell membrane, observed under the fluorescence microscope by the absorption of propidium iodide (PI). The synergistic effect of teniposide in combination with fosfomycin and gentamicin was documented by disk diffusion and checkboard assay, recording a fractional inhibitory concentration index (FICI) of 0.28 and 0.37, respectively. The drug’s action on <i>S. epidermidis</i> biofilm biomass was investigated using crystal violet (CV) and MTT. Teniposide affected biofilm viability in a dose-dependent manner, inducing, at a concentration of 3.12 <i>μ</i>g/mL, a matrix inhibition of about 42% and 61%, with a sessile metabolic activity of 54% and 24% recorded after 2 and 24 h, respectively. 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Repurposing the Antibacterial Activity of the Drug Teniposide Against Gram-Positive Bacteria
Drug repurposing is sparking considerable interest due to reduced costs and development times. The current study details the screening of teniposide, an antitumor drug, for its antibacterial activity against both Gram-positive and Gram-negative strains, with a focus on Staphylococcus epidermidis (S. epidermidis), the primary causative agent of nosocomial and transplant-related infections. The cytotoxicity was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and hemolysis assays on immortalized human keratinocyte (HaCaT) cells and human erythrocytes. After 20 h of treatment, the recorded concentrations causing 50% cytotoxicity (CC50) and hemolysis (HC50) were 33.63 and 121.55 μg/mL, respectively. The antibacterial screening employed disk diffusion, the broth microdilution method, LIVE/DEAD staining, and a time-killing test. The drug induced a growth inhibitory area in the 22–25 mm range for all Gram-positive strains. The minimum concentration that inhibited 90% of bacteria (MIC90) was 6.25 μg/mL against Staphylococcus aureus and S. epidermidis and 12.5 μg/mL versus Enterococcus faecalis, exhibiting bactericidal action. Treatment resulted in S. epidermidis cell morphology deformities and damage to the cell membrane, observed by scanning electron microscopy (SEM). Mechanism analysis revealed alterations in the selective permeability of the cell membrane, observed under the fluorescence microscope by the absorption of propidium iodide (PI). The synergistic effect of teniposide in combination with fosfomycin and gentamicin was documented by disk diffusion and checkboard assay, recording a fractional inhibitory concentration index (FICI) of 0.28 and 0.37, respectively. The drug’s action on S. epidermidis biofilm biomass was investigated using crystal violet (CV) and MTT. Teniposide affected biofilm viability in a dose-dependent manner, inducing, at a concentration of 3.12 μg/mL, a matrix inhibition of about 42% and 61%, with a sessile metabolic activity of 54% and 24% recorded after 2 and 24 h, respectively. Overall, this study suggests the potential repurposing of the anticancer drug teniposide as a therapeutic agent to counteract S. epidermidis infections.
期刊介绍:
Cellular Microbiology aims to publish outstanding contributions to the understanding of interactions between microbes, prokaryotes and eukaryotes, and their host in the context of pathogenic or mutualistic relationships, including co-infections and microbiota. We welcome studies on single cells, animals and plants, and encourage the use of model hosts and organoid cultures. Submission on cell and molecular biological aspects of microbes, such as their intracellular organization or the establishment and maintenance of their architecture in relation to virulence and pathogenicity are also encouraged. Contributions must provide mechanistic insights supported by quantitative data obtained through imaging, cellular, biochemical, structural or genetic approaches.