A Highly Active Chimeric Lysin with a Calcium-Enhanced Bactericidal Activity against <i>Staphylococcus aureus</i> In Vitro and In Vivo

• Main Authors: Xiaohong Li (Author), Shujuan Wang (Author), Raphael Nyaruaba (Author), Huan Liu (Author), Hang Yang (Author), Hongping Wei (Author)
• Format: Book
• Published: MDPI AG, 2021-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Lysins, including chimeric lysins, have recently been explored as novel promising alternatives to failing antibiotics in treating multi-drug resistant (MDR) pathogens, including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). Herein, by fusing the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) catalytic domain from the Ply187 lysin with the non-SH3b cell-wall binding domain from the LysSA97 lysin, a new chimeric lysin ClyC was constructed with Ca²⁺-enhanced bactericidal activity against all <i>S. aureus</i> strains tested, including MRSA. Notably, treating <i>S. aureus</i> with 50 μg/mL of ClyC in the presence of 100 μM Ca²⁺ lead to a reduction of 9 Log₁₀ (CFU/mL) in viable bacterial number, which was the first time to observe a lysin showing such a high activity. In addition, the effective concentration of ClyC could be decreased dramatically from 12 to 1 μg/mL by combination with 0.3 μg/mL of penicillin G. In a mouse model of <i>S. aureus</i> bacteremia, a single intraperitoneal administration of 0.1 mg/mouse of ClyC significantly improved the survival rates and reduced 2 Log₁₀ (CFU/mL) of the bacterial burdens in the organs of the infected mice. ClyC was also found stable after lyophilization without cryoprotectants. Based on the above observations, ClyC could be a promising candidate against <i>S. aureus</i> infections.

Item Description

10.3390/antibiotics10040461
2079-6382