Experimental protection of mice against lethal Staphylococcus aureus infection by novel bacteriophage phi MR11.
The protective effects of bacteriophages were assessed against experimental Staphylococcus aureus infection in mice. Of the S. aureus phages isolated in the study, phi MR11 was representatively used for all testing, because its host range was the most broad and it carries no genes for known toxins or antibiotic resistance. Intraperitoneal injections (8 x 10(8) cells) of S. aureus, including methicillin-resistant bacteria, caused bacteremia and eventual death in mice. In contrast, subsequent intraperitoneal administration of purified phi MR11 (MOI > or = 0.1) suppressed S. aureus-induced lethality. This lifesaving effect coincided with the rapid appearance of phi MR11 in the circulation, which remained at substantial levels until the bacteria were eradicated. Inoculation with high-dose phi MR11 alone produced no adverse effects attributable to the phage. These results uphold the efficacy of phage therapy against pernicious S. aureus infections in humans and suggest that phi MR11 may be a potential prototype for gene-modified, advanced therapeutic S. aureus phages.
Matsuzaki
Shigenobu
S
Department of Microbiology, Kochi Medical School, Kochi, Japan.
Yasuda
Masaharu
M
Nishikawa
Hiroshi
H
Kuroda
Masayuki
M
Ujihara
Takako
T
Shuin
Taro
T
Shen
Yuan
Y
Jin
Zhe
Z
Fujimoto
Shigeyoshi
S
Nasimuzzaman
M D
MD
Wakiguchi
Hiroshi
H
Sugihara
Shigeyoshi
S
Sugiura
Tetsuro
T
Koda
Shigeki
S
Muraoka
Asako
A
Imai
Shosuke
S
D000818:Animals; D016470:Bacteremia / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D008712:Methicillin / Q000494:pharmacology; D016106:Methicillin Resistance; D051379:Mice; D008807:Mice, Inbred BALB C; D013203:Staphylococcal Infections / Q000517:prevention & control* / Q000628:therapy; D013204:Staphylococcus Phages / Q000302:isolation & purification; D013211:Staphylococcus aureus / Q000187:drug effects / Q000821:virology
D008712:Methicillin