title: Wall Teichoic Acids Are Involved in the Medium-Induced Loss of Function of the Autolysin CD11 against Clostridium difficile.
abstract: Bacterial lysins are potent antibacterial enzymes with potential applications in the treatment of bacterial infections. Some lysins lose activity in the growth media of target bacteria, and the underlying mechanism remains unclear. Here we use CD11, an autolysin of Clostridium difficile, as a model lysin to demonstrate that the inability of this enzyme to kill C. difficile in growth medium is not associated with inhibition of the enzyme activity by medium, or the modification of the cell wall peptidoglycan. Rather, wall teichoic acids (WTAs) appear to prevent the enzyme from binding to the cells and cleaving the cell wall peptidoglycan. By partially blocking the biosynthetic pathway of WTAs with tunicamycin, cell binding improved and the lytic efficacy of CD11 was significantly enhanced. This is the first report of the mechanism of lysin inactivation in growth medium, and provides insights into understanding the behavior of lysins in complex environments, including the gastrointestinal tract.
authors.affiliation: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, US.|Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, US.
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.affiliation: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, US.
authors.forename: Elena E
authors.initials: EE
authors.lastname: Paskaleva
authors.affiliation: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, US.|Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, US.
authors.forename: Krunal K
authors.initials: KK
authors.lastname: Mehta
authors.affiliation: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, US.|Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, US.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Dordick
authors.affiliation: School of Chemical &Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, US.
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Kane
mesh_terms: D001433:Bacteriolysis; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism*; D016360:Clostridioides difficile / Q000201:enzymology*; D003470:Culture Media / Q000737:chemistry*; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000378:metabolism*; D010457:Peptidoglycan / Q000378:metabolism*; D013682:Teichoic Acids / Q000378:metabolism*
chemical_list: D003470:Culture Media; D010457:Peptidoglycan; D013682:Teichoic Acids; D009238:N-Acetylmuramoyl-L-alanine Amidase