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Cronobacter turicensis is an opportunistic foodborne pathogen that can cause a rare but sometimes lethal infection in neonates. Little is known about the virulence mechanisms and intracellular lifestyle of this pathogen. In this study, we developed an IgG monoclonal antibody (MAb; MAb 2G4) that specifically recognizes the O1 antigen of C. turicensis cells. The antilipopolysaccharide antibody bound predominantly monovalently to the O antigen and reduced bacterial growth without causing cell agglutination. Furthermore, binding of the antibody to the O1 antigen of C. turicensis cells caused a significant reduction of the membrane potential which is required to energize flagellar rotation, accompanied by a decreased flagellum-based motility. These results indicate that binding of IgG to the O antigen of C. turicensis causes a direct antimicrobial effect. In addition, this feature of the antibody enabled new insight into the pathogenicity of C. turicensis. In a tissue culture infection model, pretreatment of C. turicensis with MAb 2G4 showed no difference in adhesion to human epithelial cells, whereas invasion of bacteria into Caco-2 cells was significantly inhibited., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: Streptococcal infections are known to trigger autoimmune disorders, affecting millions worldwide. Recently, we found an association between post-streptococcal autoantibodies against Protein Disulphide Isomerase (PDI), an enzyme involved in insulin degradation and insulin resistance. This led us to evaluate associations between post-streptococcal antibodies and metabolic syndrome, as defined by the updated National Cholesterol Education Program definition, 2005., Methods and Findings: Metabolic data (HDL, triglycerides, fasting glucose, blood pressure, waist circumference, BMI, smoking), post-streptococcal antibodies (anti-Streptolysin O (ASO) and anti-PDI), and C-reactive protein (CRP, as a general inflammatory marker), were assessed in 1156 participants of the Wisconsin Sleep Cohort Study. Anti-PDI antibodies were found in 308 participants (26.6%), ASO≥100 in 258 (22.3%), and 482 (41.7%) met diagnostic criteria for metabolic syndrome. Anti-PDI antibodies but not ASO were significantly associated with metabolic syndrome [n = 1156, OR 1.463 (95% CI 1.114, 1.920), p = 0.0062; adjusted for age, gender, education, smoking]. Importantly, the anti-PDI-metabolic syndrome association remained significant after adjusting for CRP and fasting insulin., Conclusions: Post-streptococcal anti-PDI antibodies are associated with metabolic syndrome regardless of fasting insulin and CRP levels. Whereas these data are in line with a growing body of evidence linking infections, immunity and metabolism, additional studies are necessary to establish the post-streptococcal-metabolic syndrome association.

Post-streptococcal autoimmunity affects millions worldwide, targeting multiple organs including the heart, brain, and kidneys. To explore the post-streptococcal autoimmunity spectrum, we used western blot analyses, to screen 310 sera from healthy subjects with (33%) and without (67%) markers of recent streptococcal infections [anti-Streptolysin O (ASLO) or anti-DNAse B (ADB)]. A 58 KDa protein, reacting strongly with post-streptococcal sera, was identified as Protein Disulfide Isomerase (PDI), an abundant protein with pleiotropic metabolic, immunologic, and thrombotic effects. Anti-PDI autoantibodies, purified from human sera, targeted similar epitopes in Streptolysin O (SLO, P51-61) and PDI (P328-338). The correlation between post-streptococcal status and anti-human PDI auto-immunity was further confirmed in a total of 2987 samples (13.6% in 530 ASLO positive versus 5.6% in 2457 ASLO negative samples, p<0.0001). Finally, anti-PDI auto-antibodies inhibited PDI-mediated insulin degradation in vitro (n = 90, p<0.001), and correlated with higher serum insulin (14.1 iu/ml vs. 12.2 iu/ml, n = 1215, p = 0.039) and insulin resistance (Homeostatic Model Assessment (HOMA) 4.1 vs. 3.1, n = 1215, p = 0.004), in a population-based cohort. These results identify PDI as a major target of post-streptococcal autoimmunity, and establish a new link between infection, autoimmunity, and metabolic disturbances.

Study Objectives: Narcolepsy-cataplexy has long been thought to have an autoimmune origin. Although susceptibility to narcolepsy, like many autoimmune conditions, is largely genetically determined, environmental factors are involved based on the high discordance rate (approximately 75%) of monozygotic twins. This study evaluated whether Streptococcus pyogenes and Helicobacter pylori infections are triggers for narcolepsy., Design: Retrospective, case-control., Setting: Sleep centers of general hospitals., Participants: 200 patients with narcolepsy/hypocretin deficiency, with a primary focus on recent onset cases and 200 age-matched healthy controls. All patients were DQB1*0602 positive with low CSF hypocretin-1 or had clear-cut cataplexy., Measurements and Results: Participants were tested for markers of immune response to beta hemolytic streptococcus (anti-streptolysin O [ASO]; anti DNAse B [ADB]) and Helicobacter pylori [Anti Hp IgG], two bacterial infections known to trigger autoimmunity. A general inflammatory marker, C-reactive protein (CRP), was also studied. When compared to controls, ASO and ADB titers were highest close to narcolepsy onset, and decreased with disease duration. For example, ASO > or = 200 IU (ADB > or = 480 IU) were found in 51% (45%) of 67 patients within 3 years of onset, compared to 19% (17%) of 67 age matched controls (OR = 4.3 [OR = 4.1], P < 0.0005) or 20% (15%) of 69 patients with long-standing disease (OR = 4.0 [OR = 4.8], P < 0.0005]. CRP (mean values) and Anti Hp IgG (% positive) did not differ from controls., Conclusions: Streptococcal infections are probably a significant environmental trigger for narcolepsy.