The following is a summary of “Engineered Lysin, CF-370, is Active Against Antibiotic-Resistant Gram-Negative Pathogens In vitro and Synergizes with Meropenem in Experimental Pseudomonas aeruginosa Pneumonia,” published in the February 2024 issue of Infectious Diseases by Sauve et al.
As cell wall hydrolases, Gram-negative targeting lysins necessitate engineering to breach the outer membrane, enabling access to underlying peptidoglycan for effective killing.
Researchers conducted a retrospective study to assess the clinical potential of engineered lysin CF-370 against clinically significant Gram-negative pathogens through in vitro and in vivo experiments.
They determined MICs and bactericidal activity through standard methods and conducted an in vivo proof-of-concept efficacy study using a rabbit acute pneumonia model induced by Pseudomonas aeruginosa (P. aeruginosa).
The results showed that CF-370 displayed potent antimicrobial activity, with MIC50/90 values (in µg/mL) as P. aeruginosa, 1/2; Acinetobacter baumannii, 1/1; Escherichia coli, 0.25/1; Klebsiella pneumoniae, 2/4; Enterobacter cloacae, 1/4; and Stenotrophomonas maltophilia, 2/8. Additionally, CF-370 demonstrated bactericidal activity, effectiveness in serum, low resistance development, anti-biofilm properties, and synergy with antibiotics. In the pneumonia model, CF-370 alone reduced bacterial densities in the lungs, kidneys, and spleen compared to the vehicle control and showed significantly enhanced efficacy when combined with meropenem (compared to either agent alone).
Investigators concluded that engineered lysin CF-370 shows promise as a broad-spectrum antibiotic, effectively killing various clinically relevant Gram-negative bacteria in lab tests and an animal infection model.
Source: academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiae027/7608873
