A chimeolysin with extended-spectrum streptococcal host range found by an induced lysis-based rapid screening method

Abstract

The increasing emergence of multi-drug resistant streptococci poses a serious threat to public health worldwide. Bacteriophage lysins are promising alternatives to antibiotics; however, their narrow lytic spectrum restricted to closely related species is a central shortcoming to their translational development. Here, we describe an efficient method for rapid screening of engineered chimeric lysins and report a unique “chimeolysin”, ClyR, with robust activity and an extended-spectrum streptococcal host range against most streptococcal species, including S. pyogenes, S. agalactiae, S. dysgalactiae, S. equi, S. mutans, S. pneumoniae, S. suis and S. uberis, as well as representative enterococcal and staphylococcal species (including MRSA and VISA). ClyR is the first lysin that demonstrates activity against the dominant dental caries-causing pathogen as well as the first lysin that kills all four of the bovine mastitis-causing pathogens. This study demonstrates the success of the screening method resulting in a powerful lysin with potential for treating most streptococcal associated infections.

Endolysins of Bacteriophages as an Anti-Methicillin Resistant Staphylococcus aureus Infection in Children: A Narrative Review

“…Although, Endolysins completely act proprietary for each species, some endolysins have a wide host range, as shown in a study by Yang et al in 2015. They showed a unique "chimeolysin", ClyR, with robust activity, and an extended-spectrum streptococcal host range, most streptococcal species, as well as representative enterococcal and staphylococcal species (50). Similar studies have been reported that LysK, from staphylococcal phage K, has been activated against 9 Staphylococcus species from both human and bovine sources, including MRSA.…”

Antibiofilm Activities of a Novel Chimeolysin against Streptococcus mutans under Physiological and Cariogenic Conditions

“…However, no studies to date have reported on lysins effective against S. mutans biofilms. ClyR is a chimeolysin engineered from two parental streptococcal lysins and is the first lysin reported to be active against planktonic S. mutans cells (22). In the present study, we report the efficacy of ClyR in preventing and removing biofilms formed by S. mutans under both physiological and cariogenic conditions.…”

“…The swabs were placed in 400 l PBS, sonicated for 1 min, and plated on mitis salivarius-bacitracin agar plates containing 15% sucrose, 0.2 g/ml bacitracin, 0.001% potassium tellurate for enumeration of the plaque CFU. After the 3-week treatment, the serum and saliva were monitored for the presence of ClyR-specific antibodies for another 2 weeks by enzyme-linked immunosorbent assay (ELISA), as described previously (22). The body weight of each mouse was also measured weekly.…”

Physiology and Pathology of Multidrug-Resistant Bacteria: Phage-Related Therapy

“…Native CD and CWBD were joined via a linker to develop chimeolysins (e.g. Lys168-87, Lys170-87, B30-182-lyso, Ply187N-V12C and ClyR), which showed broad antibacterial spectrum [112,115]. One such chimeolysin, ClyR, effectively lyses Streptococcal spp.…”

“…(S. pyogenes, S. agalactiae, S. dysgalactiae, S. equi, S. mutans, S. pneumoniae, S. suis and S. uberis), E. faecalis and S. aureus, including MRSA [115]. The chimeolysin ClyR is also effective in killing Streptococcus mutans, which colonizes as biofilm on tooth surface [115].…”