Efficient elimination of multidrug-resistant Staphylococcus aureus by cloned lysin derived from bacteriophage phi MR11.
We report the successful purification of a cloned lysin encoded by the novel Staphylococcus aureus bacteriophage phi MR11. The lysin, designated MV-L, rapidly and completely lysed cells of a number of S. aureus strains tested, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus and a subset of vancomycin-intermediate S. aureus (VISA) in growing conditions. MV-L-mediated killing is specific to S. aureus and not to other species, except for S. simulans. MV-L exerted its staphylocidal effect synergistically with glycopeptide antibiotics against VISA. MV-L efficiently eliminated MRSA that had been artificially inoculated into the nares of mice. The intraperitoneal administration of MV-L also protected mice against MRSA septic death, without any harmful effects. Although MV-L evoked detectable levels of a humoral response in mice, the antibodies did not abolish the bacteriolytic activity. These results indicate that MV-L might be useful as a powerful therapeutic agent against multidrug-resistant S. aureus infections.
Rashel
Mohammad
M
Department of Biochemistry, Kochi Medical School, Nankoku 783-8505, Japan.
Uchiyama
Jumpei
J
Ujihara
Takako
T
Uehara
Yoshio
Y
Kuramoto
Shu
S
Sugihara
Shigeyoshi
S
Yagyu
Ken-Ichi
K
Muraoka
Asako
A
Sugai
Motoyuki
M
Hiramatsu
Keiichi
K
Honke
Koichi
K
Matsuzaki
Shigenobu
S
D000281:Administration, Intranasal; D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000302:isolation & purification; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000302:isolation & purification; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D010450:Endopeptidases / Q000008:administration & dosage / Q000096:biosynthesis; D005260:Female; D006460:Hemolysin Proteins / Q000008:administration & dosage* / Q000302:isolation & purification; D016106:Methicillin Resistance / Q000187:drug effects; D051379:Mice; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D013204:Staphylococcus Phages / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000821:virology; D020713:Vancomycin Resistance / Q000187:drug effects
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D011994:Recombinant Proteins; C021091:staphylococcal alpha-toxin; D010450:Endopeptidases; C524339:MV-L lysin, bacteriophage phiMR11