TY - JOUR
T1 - Occurrence of secondary attenuating mutations in avirulent Salmonella typhimurium vaccine strains
AU - Lockman, Hank A.
AU - Curtiss, Roy
PY - 1990/12
Y1 - 1990/12
N2 - The attenuating ΔaroA554 mutation in Salmonella typhimurium strain SL3261 was complemented in vitro by selecting for aroA+ recombinant DNA clones. SL3261 containing cloned aroA+ genes did not require exogenous phenylalanine, tryptophan, tyrosine, p-aminobenzoic acid, or dihydroxybenzoicacid for growth in defined media. Cloned aroA+ genes did not restore wild-type virulence to SL3261, however, in a murine typhoid model. The J1aroA554 mutation was transduced into S. typhimurium strain SR-11, a mouse-virulent strain recently passaged in mice. The SR-11 ΔaroA554 mutant washighly attenuated for mice challenged parenterally. The same cloned aroA+ genes isolated in SL3261 restored the virulence of the SR-11 ΔaroA554 mutant to that of wild-type SR-11. These results suggest that while the ΔaroA554 allele remains effectivein reducing S. typhimurium virulence, laboratory passage of attenuated vaccine strains may lead to the accumulation of additional attenuating defects.
AB - The attenuating ΔaroA554 mutation in Salmonella typhimurium strain SL3261 was complemented in vitro by selecting for aroA+ recombinant DNA clones. SL3261 containing cloned aroA+ genes did not require exogenous phenylalanine, tryptophan, tyrosine, p-aminobenzoic acid, or dihydroxybenzoicacid for growth in defined media. Cloned aroA+ genes did not restore wild-type virulence to SL3261, however, in a murine typhoid model. The J1aroA554 mutation was transduced into S. typhimurium strain SR-11, a mouse-virulent strain recently passaged in mice. The SR-11 ΔaroA554 mutant washighly attenuated for mice challenged parenterally. The same cloned aroA+ genes isolated in SL3261 restored the virulence of the SR-11 ΔaroA554 mutant to that of wild-type SR-11. These results suggest that while the ΔaroA554 allele remains effectivein reducing S. typhimurium virulence, laboratory passage of attenuated vaccine strains may lead to the accumulation of additional attenuating defects.
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U2 - 10.1093/infdis/162.6.1397
DO - 10.1093/infdis/162.6.1397
M3 - Article
C2 - 2230273
AN - SCOPUS:0025259938
SN - 0022-1899
VL - 162
SP - 1397
EP - 1400
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -