REDUCED VIRULENCE OF RIFAMPICIN-RESISTANT MUTANTS OF FRANCISELLA-TULARENSIS

被引:29
作者
BHATNAGAR, N
GETACHEW, E
STRALEY, S
WILLIAMS, J
MELTZER, M
FORTIER, A
机构
[1] ENTRE MED INC, ROCKVILLE, MD 20850 USA
[2] WALTER REED ARMY MED CTR, WALTER REED ARMY INST RES, DEPT CELLULAR IMMUNOL, WASHINGTON, DC 20307 USA
[3] WALTER REED ARMY MED CTR, WALTER REED ARMY INST RES, DEPT BACTERIAL DIS, WASHINGTON, DC 20307 USA
[4] UNIV KENTUCKY, MED CTR, DEPT IMMUNOL & MICROBIOL, LEXINGTON, KY USA
[5] KAISER PERMANENTE, FOOD & DRUG ADM, DERMATOL SERV, VACCINES BRANCH, ROCKVILLE, MD USA
关键词
D O I
10.1093/infdis/170.4.841
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Rifampicin-resistant mutants of a live vaccine strain (LVS) of Francisella tularensis were produced and screened for virulence in mice; 4 avirulent clones with intraperitoneal (ip) LD(50)s > 10(6) cfu, compared with 10(2) cfu for LVS, were characterized. Growth characteristics at 37 degrees C, surface envelope proteins, and lipopolysaccharide profiles of resistant mutants were identical to those of LVS. Polymerase activity of the mutants was more resistant than the enzyme from LVS to the inhibitory action of rifampicin. Growth rates for mutants and LVS were similar during the first 5 h at 42 degrees C, but viability of the mutants decreased to < 0.01% at 24 h. LVS and mutants differed in their ability to grow in vitro in host macrophages: LVS increased 580-fold over 72 h; mutants increased 33-fold. After ip inoculation of the organisms into mice, increasing numbers of LVS from peritoneal cells were isolated; mutants decreased over 4 days.
引用
收藏
页码:841 / 847
页数:7
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