biostudies-literaturePeng ZNIDDK NIH HHSNIAID NIH HHSNIGMS NIH HHS3234https://www.ebi.ac.uk/biostudies/studies/S-EPMC6336692biostudies-literatureUnknown9Clostridioides difficile is the leading cause of worldwide antibiotics-associated diarrhea. In this study, we report the construction and evaluation of a novel bacteriophage lysin-human defensin fusion protein targeting C. difficile. The fusion protein, designated LHD, is composed of two parts connected by a 3-repeating unit linker "(GGGGS)3": the catalytic domain of a lysin protein from a C. difficile bacteriophage phiC2 (LCD), and the functional domain of a human defensin protein HD5. Lytic assays showed that LHD protein had a potent lytic activity against different types of clinical C. difficile strains, including the epidemic 027, 078, 012, and 087 strains. The minimum inhibitory concentration (MIC) of LHD was 0.78 μg/ml, which was lower than the MIC of the protein LCD (1.56 μg/ml), and the MICs of metronidazole (4 μg/ml) and vancomycin (4 μg/ml). In addition, the LHD protein could lyse C. different strains in different pHs (6.0, 7.0, and 8.0). Evaluation of LHD potency in vivo using mouse model of C. difficile infection (CDI) showed that administration of the LHD protein (twice daily for 7 days) was effective in mitigating the symptoms and reducing the death from CDI. Treatment with LHD also significantly decreased the number of C. difficile spores and the toxin level in feces from the infected mice. Our data suggest that this novel lysin-human defensin fusion protein has a potential on CDI control.Frontiers in microbiologyA Novel Bacteriophage Lysin-Human Defensin Fusion Protein Is Effective in Treatment of Clostridioides difficile Infection in Mice.PMC6336692R01 AI132711K01 DK092352R03 DK112004R21 AI113470R01 GM112652Lamabadu Warnakulasuriya Patabendige HMLi CWang SCai JSun XPeng ZGide MZhu DfalseA Novel Bacteriophage Lysin-Human Defensin Fusion Protein Is Effective in Treatment of Clostridioides difficile Infection in Mice.Clostridioides difficile is the leading cause of worldwide antibiotics-associated diarrhea. In this study, we report the construction and evaluation of a novel bacteriophage lysin-human defensin fusion protein targeting C. difficile. The fusion protein, designated LHD, is composed of two parts connected by a 3-repeating unit linker "(GGGGS)3": the catalytic domain of a lysin protein from a C. difficile bacteriophage phiC2 (LCD), and the functional domain of a human defensin protein HD5. Lytic assays showed that LHD protein had a potent lytic activity against different types of clinical C. difficile strains, including the epidemic 027, 078, 012, and 087 strains. The minimum inhibitory concentration (MIC) of LHD was 0.78 μg/ml, which was lower than the MIC of the protein LCD (1.56 μg/ml), and the MICs of metronidazole (4 μg/ml) and vancomycin (4 μg/ml). In addition, the LHD protein could lyse C. different strains in different pHs (6.0, 7.0, and 8.0). Evaluation of LHD potency in vivo using mouse model of C. difficile infection (CDI) showed that administration of the LHD protein (twice daily for 7 days) was effective in mitigating the symptoms and reducing the death from CDI. Treatment with LHD also significantly decreased the number of C. difficile spores and the toxin level in feces from the infected mice. Our data suggest that this novel lysin-human defensin fusion protein has a potential on CDI control.2018-01-01T00:00:00Z20182024-11-19T21:47:51.158Z2019-03-26T22:43:42ZS-EPMC63366923068725010.3389/fmicb.2018.03234