Mutagenesis of a bacteriophage lytic enzyme PlyGBS significantly increases its antibacterial activity against group B streptococci |
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Authors: | Qi Cheng Vincent A Fischetti |
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Institution: | (1) The Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA |
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Abstract: | Group B streptococci (GBS) are the leading cause of neonatal meningitis and sepsis worldwide. Intrapartum antibiotic prophylaxis
(IAP) is the current prevention strategy given to pregnant women with confirmed vaginal GBS colonization. Due to antibiotic
resistance identified in GBS, we previously developed another strategy using a bacteriophage lytic enzyme, PlyGBS, to reduce
vaginal GBS colonization. In this study, various DNA mutagenesis methods were explored to produce PlyGBS mutants with increased
lytic activity against GBS. Several hyperactive mutants were identified that contain only the endopeptidase domain found in
the N-terminal region of PlyGBS and represent only about one-third of the wild-type PlyGBS in length. Significantly, these
mutants not only have 18–28-fold increases in specific activities compared to PlyGBS, but they also have a similar activity
spectrum against several streptococcal species. One of the hyperactive mutants, PlyGBS90-1, reduced the GBS colonization from
>5 logs of growth per mouse to <50 colony-forming units (cfu) 4 h post treatment (∼4-log reduction) using a single dose in
a mouse vaginal model. A reduction in GBS colonization before delivery should significantly reduce neonatal GBS infection
providing a safe alternative to IAP. |
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Keywords: | Group B streptococci (GBS) Streptococcus agalactiae Bacteriophage lytic enzymes DNA mutagenesis Intrapartum antibiotic prophylaxis |
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