Hefty structures of IgA and IgM complexes Immunoglobulin M (IgM) and IgA are antibody isotypes that can form higher-order secretory complexes (sIgM and sIgA), which allows them to effectively bind and neutralize antigens with low-affinity repetitive epitopes, such as those found on the surface of many bacteria and viruses. The assembly and transport of these molecules is also dependent on the joining chain (J-chain) and the polymeric immunoglobulin receptor (pIgR) secretory component (SC). The architecture of these complex, multimeric structures has remained elusive. Li et al. resolved cryo–electron microscopy structures of the sIgM-Fc pentamer in complex with the J-chain and SC. Using similar techniques, Kumar et al. visualized dimeric, tetrameric, and pentameric structures of secretory sIgA-Fc interacting with the J-chain and SC. Both groups report highly similar mechanisms wherein the J-chain serves as a template for antibody oligomerization. An unanticipated, amyloid-like assembly of the oligomerized structure is present in both cases, with the J-chain conferring asymmetry for pIgR binding and transcytosis. These studies may inform structure-based engineering of these molecules for future therapeutic purposes. Science , this issue p. 1014 , p. 1008
The bactericidal effects of Q-35, sparfloxacin, tosufloxacin, and ofloxacin on 18 strains of methicillin-resistant Staphylococcus aureus (MRSA) and 3 strains of Staphylococcus epidermidis were studied by a viable-count method. Staphylococci as used in this study were clearly divided into two groups with respect to their susceptibilities to sparfloxacin. MICs of Q-35 and tosufloxacin were 0.05 to 0.78 microgram/ml for sparfloxacin-susceptible strains (MICs, 0.05 to 0.2 microgram/ml) and 1.56 to 12.5 micrograms/ml for sparfloxacin-resistant strains (6.25 to 25 micrograms/ml). All the sparfloxacin-resistant strains of MRSA tested contained the gyrA mutation at codon 84. Time-kill studies showed that Q-35 decreased the viable counts from approximately 10(7) CFU/ml to 10(3) to 10(5) CFU/ml within 3 h at concentrations greater than the MICs against both sparfloxacin-susceptible and -resistant strains. In contrast, sparfloxacin, tosufloxacin, and ofloxacin produced bacteriostatic effects at 3 h after exposure against sparfloxacin-resistant strains at concentrations which were greater than the respective MICs, whereas these quinolones were bactericidal against sparfloxacin-susceptible strains. The rapid bactericidal activities of Q-35 against sparfloxacin-resistant MRSA were reduced when the methoxy group of Q-35 at the 8 position was substituted with fluorine or hydrogen. Thus, our data suggest that the introduction of a methoxy group into the 8 position of quinolones contributes to the bactericidal activities of fluoroquinolones against quinolone-resistant staphylococci.
