Results for the GB2 mutant were identical to those obtained with GB11 (data not shown). triggering a cross-reactive immune response after an infection (1). There is strong but indirect evidence for the pathogenic role of molecular mimicry in Guillain-Barr syndrome (GBS), an acute peripheral polyneuropathy and the most frequent cause of acute neuromuscular paralysis (2). Therefore, GBS is an excellent model disease to Paliperidone study both microbial and host factors involved in molecular mimicry. The most frequently identified triggering agent of GBS is is the leading causative agent of bacterial gastroenteritis worldwide, and it has recently also been associated with neoplastic disease of the gut (5). Acute-phase sera of GBS patients contain high titers of antibodies directed against gangliosides, membrane glycolipids that are highly enriched in nervous tissue (6). Biochemical and serological studies have identified various ganglioside-mimicking structures in the lipo-oligosaccharides (LOS) of the cell wall (7), and cross-reactive antibodies between LOS and gangliosides have been demonstrated in serum from GBS patients (6). Ganglioside-mimicking structures are found more frequently in neuropathy-associated strains than in strains isolated from patients with diarrhea (8). An important feature in ganglioside mimicry is Paliperidone the presence of sialic acid (strains isolated from Dutch patients with GBS or its variant, Miller Fisher syndrome (MFS) (10, 11). Characterization of the isolates by phenotypic and molecular methods showed that no clustering of GBS/MFSCassociated strains occurred when these were compared with control strains (10, 12). The availability of a database with detailed serological and clinical data of the Dutch GBS/MFS patients provides a unique opportunity for a systematic search for bacterial GBS/MFSCassociated virulence factors and correlations with specific immune responses and clinical presentation. We recently reported the association between the presence of the (genes involved in LOS biosynthesis may be crucial for the induction of the anti-ganglioside immune response that leads to GBS. Therefore, we analyzed the LOS biosynthesis gene locus of GBS/MFSCassociated strains. We found that specific types of the LOS biosynthesis locus are associated with GBS, and this finding led to the identification of potential GBS marker genes in gene knockout mutants, including mouse immunization experiments, demonstrated that these genes are crucial for the induction of anti-ganglioside antibodies. Results Specific classes of the LOS biosynthesis gene locus are associated with neuropathy and ganglioside mimicry. In strains. Previously, we had described 3 different gene compositions or classes of the LOS locus in (15). Since then, the DNA sequences of several additional LOS loci were deposited in GenBank (http://www.ncbi.nlm.nih.gov/Genbank/), and there are now 5 distinct classes (Figure ?(Figure11). Open in a separate window Figure 1 Genetic organization of the 5 AIbZIP different classes of the LOS biosynthesis locus. The distance between the scale marks is 1 kb. The direction of the arrows indicates the direction of transcription. Corresponding homologous genes have the same number with a letter for the LOS locus class added. For and the corresponding Cj gene numbers of the genome strain NCTC 11168 are given. The 5 LOS classes are based on DNA sequences of the following strains (GenBank accession number): class A: OH4384 (AF130984), OH4382 (AF167345), HS:4 (AF215659), HS:10 (AF400048), HS:19 (AF167344), HS:41 (AY044868); class B: HS:23 (AF401529), HS:36 (AF401528); class C: NCTC 11168 (AL139077), HS:1 (AY044156), HS:2 (AF400047); class D: LIO87 (AF400669); class E: 81116 (AF343914 and AJ131360). The proposed functions for the strains, we determined the class of LOS locus (classes ACE) in a collection of 21 neuropathy-associated and 21 control strains isolated from patients with uncomplicated enteritis. All the strains used in this study were positive for 1 of the 5 identified LOS locus classes. In addition, we analyzed the individual Paliperidone class A/B and class C genes by PCR RFLP and hybridization analysis and found that the LOS gene content in the strains was in agreement with their class of LOS locus (data not shown). The class A LOS locus was overrepresented in the.