We recovered a newly recognized spirochete from the blood, skin lesions (erythema chronicum migrans [ECM]), or cerebrospinal fluid of 3 of 56 patients with Lyme disease and from 21 of 110 nymphal or adult lxodes dammini ticks in Connecticut. These isolates and the original one from l. dammini appeared to have the same morphologic and immunologic features. In patients, specific IgM antibody titers usually reached a peak between the third and sixth week after the onset of disease; specific IgG antibody titers rose slowly and were generally highest months later when arthritis was present. Among 40 patients who had early disease only (ECM alone), 90 per cent had an elevated IgM titer (greater than or equal to 1:128) between the ECM phase and convalescence. Among 95 patients with later manifestations (involvement of the nervous system, heart, or joints), 94 per cent had elevated titers of IgG (greater than or equal to 1:128). In contrast, none of 80 control subjects had elevated IgG titers, and only three control patients with infectious mononucleosis had elevated IgM titers. We conclude that the I. dammini spirochete is the causative agent of Lyme disease.
The antibody response to the Ixodes dammini spirochete was determined in 41 serial serum samples from 12 patients with Lyme disease. By enzyme-linked immunosorbent assay (ELISA), 11 of the 12 patients had higher titers of specific IgM antibody (greater than 1:200) during early disease than did 40 control subjects. Specific IgM antibody titers, which correlated with total amounts of IgM antibody (P less than .001), sometimes remained elevated throughout the illness. During neuritis, nine of 10 patients had higher specific IgG antibody titers (greater than 1:200) than did controls, and when arthritis was present, all had such titers, which remained elevated after months of remission. In the ELISA, antibody responses determined by single or serial dilutions were similar, but the ELISA was more sensitive and specific than was immunofluorescence. Adsorption of sera with Borrelia hermsii generally resulted in a fourfold decrease in titers of cross-reactive antibodies, but the titers of sera from patients with Lyme disease were also reduced. Currently, the ELISA, without adsorption, is the best diagnostic test for Lyme disease.
We compared immunoblotting and indirect enzyme-linked immunosorbent assay (ELISA) using different antigen preparations to test for antibody to Borrelia burgdorferi in patients with early Lyme disease. With immunoblotting, 16 (53%) of 30 patients had positive tests in acute-phase sera and 25 (83%) had them in convalescent-phase sera. Among 64 controls, false-positive results were obtained in only three individuals with syphilis and in one hospitalized patient with renal allograft rejection. Among the patients with Lyme disease, both IgM and IgG antibodies most commonly bound to the 41-kilodalton (kDa) flagellar antigen, but many patients had binding to other components, particularly those of 25, 55, 58, or 66 kDa, and the order of their appearance was variable. Compared with indirect ELISA (using sonicated whole spirochetes or a flagellin-enriched fraction as the antigen preparation), more patients with Lyme disease had positive tests by immunoblotting, and fewer control subjects had false-positive results. Our results indicate that immunoblotting is superior to indirect ELISA for diagnosing early Lyme disease.
Viomycin and capreomycin belong to the tuberactinomycin family of antibiotics, which are among the most effective antibiotics against multidrug-resistant tuberculosis. Here we present two crystal structures of the 70S ribosome complexed with three tRNAs and bound to either viomycin or capreomycin at 3.3 and 3.5 Å resolution, respectively. Both antibiotics bind to the same site on the ribosome, which lies at the interface between helix 44 (h44) of the small ribosomal subunit and Helix 69 (H69) of the large ribosomal subunit. The structures of these complexes suggest that the tuberactinomycins inhibit translocation by stabilizing the tRNA in the A site in the pre-translocation state. In addition these structures show that the tuberactinomycins bind adjacent to the paromomycin and hygromycin B antibiotics, which may enable the development of new derivatives of tuberactinomycins that are effective against drug resistant strains.
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