SALMONELLA-TYPHIMURIUM AROA, HTRA, AND AROD HTRA MUTANTS CAUSE PROGRESSIVE INFECTIONS IN ATHYMIC (NU NU) BALB/C MICE/

Athymic (nu/nu) BALB/c mice and their euthymic (nu/+) littermates were inoculated intravenously with lire attenuated vaccine strains of Salm onella typhimurium. All strains caused progressive infections in the a thymic mice but not in their euthymic littermates. Athymic mice given strain SL3261, an aroA derivative of SL1344, in doses between log 4.7 and 5.7 CFU were all severely ill and were killed by weeks 4 to 5, Ath ymic mice given log 4.7 CPU of a derivative of S. typhimurium C5 carry ing a mutation in htrA, encoding a stress protein, were ill and were k illed by week 7 in one experiment but survived to week 13 in another. Athymic mice given log 4.6 CFU of a C5 aroD htrA double mutant were il l and were killed at week 7. Athymic mice given SL3261 had high bacter ial counts in the reticuloendothelial system at 4 weeks, Athymic mice given SL3261 or C5 htr-A made immunoglobulin G3 (IgG3) (and to a lesse r extent IgM) antibody to lipopolysaccharide (LPS), whereas euthymic m ice made IgM, IgG1, IgG2a, IgG2b, and IgG3 anti-LPS antibodies, The re sults indicate that both aroA and htrA strains will produce slow, prog ressively lethal infections in athymic mice, that the Ita-A strain is more attenuated than the aroA strain as measured by lime to death in t his model, and that IgG3 anti-LPS antibody alone cannot suppress the p rogress of infections by very attenuated strains in athymic mice.