Selective antimicrobial activity of cell lytic enzymes in a bacterial consortium

Appl Microbiol Biotechnol. 2019 Sep;103(17):7041-7054. doi: 10.1007/s00253-019-09955-0. Epub 2019 Jun 15.

Abstract

The role that the complex microbial communities play in human and environmental health cannot be understated. The increased information about community complexity, as well as the overuse of broad-spectrum antibiotics, suggest that new approaches to target specific organisms within a community context are essential towards new antimicrobial therapies. Here, we have assessed the activity and selectivity of two cell wall lytic enzymes, lysostaphin (Lst) and PlyPH, in the presence of multiple bacteria and under varied media conditions. Lst and PlyPH target the clinically relevant pathogens Staphylococcus aureus and Bacillus cereus, respectively. Lst was effective under all conditions resulting in ~ 4-log and ~ 3-log reduction at 100 μg/mL in actively growing monoculture and co-culture, respectively. PlyPH was also selective but less active and more susceptible to media and cell population changes. Lst and PlyPH activities could be increased in supernatants from actively growing cultures in the presence of a protease inhibitor cocktail, suggesting a possible role played by proteases secreted during cell growth in reducing lytic enzyme activity. This work demonstrates the utility of cell wall lytic enzymes for targeted pathogen killing or microbial community remodeling.

Keywords: Cell lytic enzymes; Lysostaphin; Microbial community; PlyPH; Selective antimicrobial activity; Skin microbiome.

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Bacillus cereus / drug effects
  • Bacillus cereus / growth & development
  • Bacillus cereus / metabolism
  • Biofilms / drug effects
  • Biofilms / growth & development
  • Cell Wall / drug effects*
  • Coculture Techniques
  • Culture Media / chemistry
  • Lysostaphin / pharmacology
  • Microbial Consortia / drug effects*
  • Peptide Hydrolases / analysis
  • Peptide Hydrolases / metabolism
  • Protease Inhibitors / pharmacology
  • Species Specificity
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / metabolism

Substances

  • Anti-Infective Agents
  • Culture Media
  • Protease Inhibitors
  • Peptide Hydrolases
  • Lysostaphin