LysGH15, a novel bacteriophage lysin, protects a murine bacteremia model efficiently against lethal methicillin-resistant Staphylococcus aureus infection.
Phage-coded lysin is an enzyme that destroys the cell walls of bacteria. Phage lysin could be an alternative to conventional antibiotic therapy against pathogens that are resistant to multiple antibiotics. In this study, a novel staphylococcal phage, GH15, was isolated, and the endogenous lytic enzyme (LysGH15) was expressed and purified. The lysin LysGH15 displayed a broad lytic spectrum; in vitro treatment killed a number of Staphylococcus aureus strains rapidly and completely, including methicillin-resistant S. aureus (MRSA). In animal experiments, a single intraperitoneal injection of LysGH15 (50 μg) administered 1 h after MRSA injections at double the minimum lethal dose was sufficient to protect mice (P < 0.01). Bacteremia in unprotected mice reached colony counts of about 10(7) CFU/ml within 3.5 h after challenge, whereas the mean colony count in lysin-protected mice was less than 10(4) CFU/ml (and ultimately became undetectable). These results indicate that LysGH15 can kill S. aureus in vitro and can protect mice efficiently from bacteremia in vivo. The phage lysin LysGH15 might be an alternative treatment strategy for infections caused by MRSA.
College of Animal Science and Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun 130062, People's Republic of China.
Jingmin
J
Gu
Wei
W
Xu
Liancheng
L
Lei
Jing
J
Huang
Xin
X
Feng
Changjiang
C
Sun
Chongtao
C
Du
Jing
J
Zuo
Yang
Y
Li
Taofeng
T
Du
Linxi
L
Li
Wenyu
W
Han
D000818:Animals; D016470:Bacteremia / Q000382:microbiology / Q000517:prevention & control*; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability / Q000187:drug effects; D008969:Molecular Sequence Data; D009088:Mucoproteins / Q000008:administration & dosage* / Q000235:genetics / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D013204:Staphylococcus Phages / Q000201:enzymology* / Q000302:isolation & purification; D016019:Survival Analysis; D016896:Treatment Outcome; D014764:Viral Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000302:isolation & purification
D004279:DNA, Viral; D009088:Mucoproteins; D014764:Viral Proteins; C010393:lysin, gastropoda