Guillain-Barré Syndrome-related campylobacter jejuni in Bangladesh: ganglioside mimicry and cross-reactive antibodies

BACKGROUND: <br/> Campylobacter jejuni is the predominant antecedent infection in Guillain-Barré syndrome (GBS). Molecular mimicry and cross-reactive immune responses to C. jejuni lipo-oligosaccharides (LOS) precipitate the development of GBS, although this mechanism has not been established in patients from developing countries. We determined the carbohydrate mimicry between C. jejuni LOS and gangliosides, and the cross-reactive antibody response in patients with GBS in Bangladesh.<br/> METHODOLOGY:<br/> Sera from 97 GBS patients, and 120 neurological and family controls were tested for antibody reactivity against LOS from C. jejuni isolates from GBS patients in Bangladesh (BD-07, BD-39, BD-10, BD-67 and BD-94) by enzyme-linked immunosorbent assay (ELISA). Cross-reactivity to LOS was determined by ELISA. The LOS outer core structures of C. jejuni strains associated with GBS/MFS were determined by mass spectrometry.<br/> PRINCIPLE FINDINGS:<br/> IgG antibodies to LOS from C. jejuni BD-07, BD-39, BD-10, and BD-67 IgG antibodies were found in serum from 56%, 58%, 14% and 15% of GBS patients respectively, as compared to very low frequency (<3%) in controls (p<0.001). Monoclonal antibodies specific for GM1 and GD1a reacted strongly with LOS from the C. jejuni strains (BD-07 and BD-39). Mass spectrometry analysis confirmed the presence of GM1 and GD1a carbohydrate mimics in the LOS from C. jejuni BD-07 and BD-39. Both BD-10 and BD-67 express the same LOS outer core, which appears to be a novel structure displaying GA2 and GD3 mimicry. Up to 90-100% of serum reactivity to gangliosides in two patients (DK-07 and DK-39) was inhibited by 50 µg/ml of LOS from the autologous C. jejuni isolates. However, patient DK-07 developed an anti-GD1a immune response while patient DK-39 developed an anti-GM1 immune response.<br/> CONCLUSION:<br/> Carbohydrate mimicry between C. jejuni LOS and gangliosides, and cross-reactive serum antibody precipitate the majority of GBS cases in Bangladesh

A systematic review and meta-analysis on Staphylococcus aureus carriage in psoriasis, acne and rosacea

textabstractStaphylococcus aureus might amplify symptoms in chronic inflammatory skin diseases. This study evaluates skin and mucosal colonization with S. aureus in patients with psoriasis, acne and rosacea. A systematic literature search was conducted. Both odds ratios (OR) for colonization in patients versus controls and the prevalence of colonization in patients are reported. Fifteen articles about psoriasis and 13 about acne (12 having a control group) were included. No study in rosacea met our inclusion criteria. For psoriasis, one study out of three controlled studies showed increased skin colonization (OR 18.86; 95 % confidence interval [CI] 2.20–161.99). Three out of the five studies that reported on nasal colonization showed significant ORs varying from 1.73 (95 % CI 1.16–2.58) to 14.64 (95 % CI 2.82–75.95). For acne one of the three studies that evaluated skin colonization reported a significant OR of 4.16 (95 % CI 1.74–9.94). A relation between nasal colonization and acne was not found. Limitations in study design and low sample sizes should be taken into consideration when interpreting the results. Colonisation with S. aureus seems to be increased in patients with psoriasis. This bacterial species, known for its potential to induce long-lasting inflammation, might be involved in psoriasis pathogenesis. Information on acne is limited. Prospective controlled studies should further investigate the role of S. aureus in chronic inflammatory skin diseases

Development of a species-specific polymerase chain reaction assay for Gardnerella vaginalis

The nucleotide sequence of the region between the 16S and 23S rRNA genes of the facultative anaerobic bacteriumGardnerella vaginalishas been determined, together with the 5′ proximal 500 nucleotides of the 23S rRNA gene. Regions suited for the development of specific, probe-confirmable polymerase chain reaction (PCR) assays were selected. PCR assays were evaluated with respect to sensitivity and specificity, the latter in comparison with a number ofG. vaginalisreference strains and closely related species likeBifidobacteriumspp. In an initial diagnostic study it appeared that the PCR test detectedG. vaginalisin 40% of women irrespective of their clinical status. Ten out of 11 patients suffering from bacterial vaginosis as defined on the basis of clinical parameters were carryingG. vaginalis

Discordant bioinformatic predictions of antimicrobial resistance from whole-genome sequencing data of bacterial isolates: an inter-laboratory study.

Antimicrobial resistance (AMR) poses a threat to public health. Clinical microbiology laboratories typically rely on culturing bacteria for antimicrobial-susceptibility testing (AST). As the implementation costs and technical barriers fall, whole-genome sequencing (WGS) has emerged as a 'one-stop' test for epidemiological and predictive AST results. Few published comparisons exist for the myriad analytical pipelines used for predicting AMR. To address this, we performed an inter-laboratory study providing sets of participating researchers with identical short-read WGS data from clinical isolates, allowing us to assess the reproducibility of the bioinformatic prediction of AMR between participants, and identify problem cases and factors that lead to discordant results. We produced ten WGS datasets of varying quality from cultured carbapenem-resistant organisms obtained from clinical samples sequenced on either an Illumina NextSeq or HiSeq instrument. Nine participating teams ('participants') were provided these sequence data without any other contextual information. Each participant used their choice of pipeline to determine the species, the presence of resistance-associated genes, and to predict susceptibility or resistance to amikacin, gentamicin, ciprofloxacin and cefotaxime. We found participants predicted different numbers of AMR-associated genes and different gene variants from the same clinical samples. The quality of the sequence data, choice of bioinformatic pipeline and interpretation of the results all contributed to discordance between participants. Although much of the inaccurate gene variant annotation did not affect genotypic resistance predictions, we observed low specificity when compared to phenotypic AST results, but this improved in samples with higher read depths. Had the results been used to predict AST and guide treatment, a different antibiotic would have been recommended for each isolate by at least one participant. These challenges, at the final analytical stage of using WGS to predict AMR, suggest the need for refinements when using this technology in clinical settings. Comprehensive public resistance sequence databases, full recommendations on sequence data quality and standardization in the comparisons between genotype and resistance phenotypes will all play a fundamental role in the successful implementation of AST prediction using WGS in clinical microbiology laboratories

No antidepressant effects of low intensity transcranial pulsed electromagnetic fields for treatment resistant depression

Background: Noninvasive neurostimulation with transcranial Pulsed Electromagnetic Fields (tPEMF) may be a promising method for treatment resistant depression (TRD). Studies shown substantial improvement of depressive symptoms in patients with TRD, but there is no information on long-term antidepressant effects. The aim of this study was to investigate the short- and long-term efficacy of tPEMF in participants with TRD. Methods: Eligible participants with TRD in this sham-controlled double-blind multicenter trial were randomly assigned to five weeks either daily active or sham tPEMF. Severity of depression and anxiety was assessed preand directly post-treatment and five and fifteen weeks post-treatment. Primary outcome was change on the 17item Hamilton depression rating scale directly post-treatment. Secondary outcome was change on the Hamilton17 during follow-up and change on the Inventory of Depressive Symptomatology Self-Report and the Beck Anxiety Index. Results: Of the 55 included participants, 50 completed the treatment protocol. Depressive symptoms improved over time in both groups. The improvement continued until the last follow-up measure. There was no difference in outcome between the active and the sham group on change in depression post-treatment or on any secondary measure. Conclusion: Treatment with this type of active tPEMF was not superior to sham in patients with TRD. This is in contrast to a previous study using a similar design and power calculation, but a higher magnetic field strength, that reported improvement of depression after treatment with tPEMF compared to sham. An important limitation of our study was the fact that no different dosing regimens were tried

Biofilm associated genotypes of multiple antibiotic resistant Pseudomonas aeruginosa

Background: Pseudomonas aeruginosa is a ubiquitous environmental microorganism and also a common cause of infection. Its ability to survive in many different environments and persistently colonize humans is linked to its presence in biofilms formed on indwelling device surfaces. Biofilm promotes adhesion to, and survival on surfaces, protects from desiccation and the actions of antibiotics and disinfectants. Results: We examined the genetic basis for biofilm production on polystyrene at room (22 °C) and body temperature (37 °C) within 280 P. aeruginosa. 193 isolates (69 %) produced more biofilm at 22 °C than at 37 °C. Using GWAS and pan-GWAS, we found a number of accessory genes significantly associated with greater biofilm production at 22 °C. Many of these are present on a 165 kb region containing genes for heavy metal resistance (arsenic, copper, mercury and cadmium), transcriptional regulators and methytransferases. We also discovered multiple core genome SNPs in the A-type flagellin gene and Type II secretion system gene xpsD. Analysis of biofilm production of isolates of the MDR ST111 and ST235 lineages on stainless-steel revealed several accessory genes associated with enhanced biofilm production. These include a putative translocase with homology to a Helicobacter pylori type IV secretion system protein, a TA system II toxin gene and the alginate biosynthesis gene algA, several transcriptional regulators and methytransferases as well as core SNPs in genes involved in quorum sensing and protein translocation. Conclusions: Using genetic association approaches we discovered a number of accessory genes and core-genome SNPs that were associated with enhanced early biofilm formation at 22 °C compared to 37 °C. These included a 165 kb genomic island containing multiple heavy metal resistance genes, transcriptional regulators and methyltransferases. We hypothesize that this genomic island may be associated with overall genotypes that are environmentally adapted to survive at lower temperatures. Further work to examine their importance in, for example gene-knockout studies, are required to confirm their relevance. GWAS and pan-GWAS approaches have great potential as a first step in examining the genetic basis of novel bacterial phenotypes

Murine Model for Measuring Effects of Humanized-Dosing of Antibiotics on the Gut Microbiome.

There is a current need for enhancing our insight in the effects of antimicrobial treatment on the composition of human microbiota. Also, the spontaneous restoration of the microbiota after antimicrobial treatment requires better understanding. This is best addressed in well-defined animal models. We here present a model in which immune-competent or neutropenic mice were administered piperacillin-tazobactam (TZP) according to human treatment schedules. Before, during and after the TZP treatment, fecal specimens were longitudinally collected at established intervals over several weeks. Gut microbial taxonomic distribution and abundance were assessed through culture and molecular means during all periods. Non-targeted metabolomics analyses of stool samples using Quadrupole Time of Flight mass spectrometry (QTOF MS) were also applied to determine if a metabolic fingerprint correlated with antibiotic use, immune status, and microbial abundance. TZP treatment led to a 5-10-fold decrease in bacterial fecal viability counts which were not fully restored during post-antibiotic follow up. Two distinct, relatively uniform and reproducible restoration scenarios of microbiota changes were seen in post TZP-treatment mice. Post-antibiotic flora could consist of predominantly Firmicutes or, alternatively, a more diverse mix of taxa. In general, the pre-treatment microbial communities were not fully restored within the screening periods applied. A new species, closely related t

Can Campylobacter coli induce Guillain-Barré syndrome?

Campylobacter jejuni enteritis is the most frequently identified infection preceding the Guillain-Barr\ue9 syndrome (GBS) and neural damage is thought to be induced through molecular mimicry between C. jejuni lipo-oligosaccharide (LOS) and human gangliosides. It has been questioned whether or not other Campylobacter species, including C. curvus, C. upsaliensis and C. coli, could be similarly involved. This is relevant because it would imply that bacterial factors considered important in the aetiology of GBS crossed species barriers. Two prior reports have appeared where C. coli was putatively associated with a case of GBS.Peer reviewed: YesNRC publication: Ye