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ARS Home » Midwest Area » Peoria, Illinois » National Center for Agricultural Utilization Research » Renewable Product Technology Research » Research » Publications at this Location » Publication #405494
Research Project: Antimicrobials for Biorefining and Agricultural Applications

Location: Renewable Product Technology Research

Title: Synergistic targeting pathogenic enterococci with phage-encoded peptidoglycan hydrolases and wall teichoic acid inhibitors

Author
item STAUBLI, SAMUEL - Eth Zurich
item RANZONI, FLAVIO - Eth Zurich
item Price, Neil
item SHEN, YANG - Eth Zurich
item LOESSNER, MARTIN - Eth Zurich

Submitted to: Swiss Society of Microbiology
Publication Type: Abstract Only
Publication Acceptance Date: 8/30/2023
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Antibiotic-resistant enterococci are on the rise and pose a great threat to humankind. Future bacterial infections will inevitably become increasingly difficult to treat due to limited drug options, intensifying the need to develop effective alternatives Endolysins are bacteriophage-derived peptidoglycan hydrolases and exhibit a great potential to kill Gram-positive bacteria in a specific and effective way. They act by cleaving the conserved bacterial peptidoglycan (PG) structure thereby inducing osmatic bacterial lysis. However, their bacteriolytic efficiency is often hampered by the presence of cell wall-associated polysaccharides, namely wall teichoic acids (WTA), which restrict the access of the endolysin to PG. To overcome this limitation, we propose to use tunicamycin, a known WTA-specific inhibitor to enhance the bacteriolytic activity of enterococcal endolysins. The enterococcal endolysin PlyV12 consists of one enzymatic active domain (EAD) and one cell wall binding domain (CBD). The EAD inherits a functional amidase cleaving the bond between the peptidoglycan sugar backbone and the peptide moiety. The combination of tunicamycin and PlyV12 in a time kill assay was significantly more effective compared to using each agent alone. Interestingly, no synergy was observed when applying tunicamycin with other non-amidase enterococcal endolysins, suggesting this synergistic effect could be amidase-dependent. To further explore the underlying mechanism and mode of action, fluorescent-tagged PlyV12 CBD and tunicamycin-derivatives were constructed and explored under the fluorescence microscope. Our data support further development of endolysins and modified tunicamycins as effective therapeutics against enterococcal infections.