A Novel Bacteriophage Lysin-Human Defensin Fusion Protein Is Effective in Treatment of Infection in Mice

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2019 Jan 29

PMID 30687250

Citations 16

Authors

Zhong Peng

Shaohui Wang

Mussie Gide

Duolong Zhu

Hiran Malinda Lamabadu Warnakulasuriya Patabendige

Chunhui Li

Jianfeng Cai

Xingmin Sun

Affiliations

Soon will be listed here.

Abstract

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 . The fusion protein, designated LHD, is composed of two parts connected by a 3-repeating unit linker "(GGGGS)": the catalytic domain of a lysin protein from a bacteriophage phiC2 (LCD), and the functional domain of a human defensin protein HD. Lytic assays showed that LHD protein had a potent lytic activity against different types of clinical 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 strains in different pHs (6.0, 7.0, and 8.0). Evaluation of LHD potency using mouse model of 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 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.

Citing Articles

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