We studied 21 strains of amikacin-resistant Serratia marcescens from three different U.S. cities, Twenty of the 21 strains contained conjugative R plasmids mediating gentamicin and tobramycin resistance. Amikacin-resistant S. marcescens from two cities predominated in protracted outbreaks. Conversely, the amikacin-resistant Charleston strain (serotype 02/03:nonmotile) was isolated from only four patients during an outbreak of gentamicin- and tobramycin resistant, amikacin-susceptible S. marcescens (serotype O19:O17). Five different representative amikacin-resistant S. marcescens, each containing a single conjugative plasmid, elaborated a nontransferable aminoglycoside (6')-N-acetyltransferase [AAC(6')] with similar substrate profiles in addition to other transferable aminoglycoside-modifying enzymes. One amikacin-resistant S. marcescens cured of its plasmid and another naturally occurring plasmid-free amikacin-resistant S. marcescens elaborated only AAC(6')-1. These data support the concept of a chromosomal locus in S. marcescens for AAC(6')-1 which commonly coexists with plasmid-mediated genes for aminoglycoside-modifying enzymes.

While it has been shown that estradiol treatment accelerates the onset of lupus nephritis with autoantibody production and kidney damage in both male and female lupus-prone mice, the specific mechanism(s) involved are unknown. Our previous work has shown that alterations in Id(LN)F(1)-reactive T cells and Id(LN)F(1)+ antibodies correlated closely with the onset of autoimmune nephritis in female F(1) progeny of SWR and NZB (SNF(1)) mice, supporting a critical role for the Id(LN)F(1) idiotype in the development of disease. Since male SNF(1) mice normally do not develop nephritis, we tested whether administration of 17β-estradiol (E-2) to male SNF(1) mice would increase Id(LN)F(1) IgG levels and autoreactive T cells, and further, induce nephritis. We found that E-2-treated male SNF(1) mice developed nephritis with the same time course and mean survival as normal female SNF(1) mice. Moreover, it appeared that the mechanism involved increased serum Id(LN)F(1)(+)IgG and its deposition in kidney glomeruli, preceded by a striking twofold increase in T-lymphocytes expressing the memory phenotype (CD44(+)CD45RB(lo)) predominantly in the Id(LN)F(1)-reactive T-cell population. In addition, we noted that cells with this phenotype were increased in the nephritic kidneys of treated mice, suggesting a direct involvement of those cells in the renal pathology. E-2 treatment also induced increased numbers of pathogenic Id(LN)F(1)+ antibody-producing B cells and elevated presentation of pathogenic Id(LN)F(1)+ peptide. Taken together, these results suggest a mechanism of E-2-induced acceleration of autoimmune disease in lupus-prone mice may involve expansion of autoreactive idiotypic T and B-cell populations.