Metagenomic insights of the infant microbiome community structure and function across multiple sites in the United States

The gut microbiome plays an important role in early life, protecting newborns from enteric pathogens, promoting immune system development and providing key functions to the infant host. Currently, there are limited data to broadly assess the status of the US healthy infant gut microbiome. To address this gap, we performed a multi-state metagenomic survey and found high levels of bacteria associated with enteric inflammation (e.g. Escherichia, Klebsiella), antibiotic resistance genes, and signatures of dysbiosis, independent of location, age, and diet. Bifidobacterium were less abundant than generally expected and the species identified, including B. breve, B. longum and B. bifidum, had limited genetic capacity to metabolize human milk oligosaccharides (HMOs), while B. infantis strains with a complete capacity for HMOs utilization were found to be exceptionally rare. Considering microbiome composition and functional capacity, this survey revealed a previously unappreciated dysbiosis that is widespread in the contemporary US infant gut microbiome

Recovery and identification of emerging campylobacteraceae from food

End of Project ReportThe family Campylobacteraceae includes 23 different species of Campylobacter and Arcobacter.To date, clinical and epidemiological interest has focused almost exclusively on just two of these species, C. jejuni and C. coli. Current routine examination methods for both clinical and food samples look exclusively for these two species. Recent clinical research indicates that some of the other, previously ignored Campylobacter species may be linked to human infection. The focus of this research was to develop a routine procedure which would allow recovery of all 23 species of Campylobacteraceae from food samples

Recovery and identification of emerging Campylobacteraceae from food

End of project reportThe family Campylobacteraceae includes 23 different species of Campylobacter and Arcobacter.To date, clinical and epidemiological interest has focused almost exclusively on just two of these species, C. jejuni and C. coli. Current routine examination methods for both clinical and food samples look exclusively for these two species. Recent clinical research indicates that some of the other, previously ignored Campylobacter species may be linked to human infection. The focus of this research was to develop a routine procedure which would allow recovery of all 23 species of Campylobacteraceae from food samples

Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction.

We describe a severe congenital myasthenic syndrome (CMS) caused by two missense mutations in the gene encoding the muscle specific receptor tyrosine kinase (MUSK). The identified MUSK mutations M605I and A727V are both located in the kinase domain of MuSK. Intracellular microelectrode recordings and microscopy studies of the neuromuscular junction conducted in an anconeus muscle biopsy revealed decreased miniature endplate potential amplitudes, reduced endplate size and simplification of secondary synaptic folds, which were consistent with postsynaptic deficit. The study also showed a striking reduction of the endplate potential quantal content, consistent with additional presynaptic failure. Expression studies in MuSK deficient myotubes revealed that A727V, which is located within the catalytic loop of the enzyme, caused severe impairment of agrin-dependent MuSK phosphorylation, aggregation of acetylcholine receptors (AChRs) and interaction of MuSK with Dok-7, an essential intracellular binding protein of MuSK. In contrast, M605I, resulted in only moderate impairment of agrin-dependent MuSK phosphorylation, aggregation of AChRs and interaction of MuSK with Dok-7. There was no impairment of interaction of mutants with either the low-density lipoprotein receptor-related protein, Lrp4 (a co-receptor of agrin) or with the mammalian homolog of the Drosophila tumorous imaginal discs (Tid1). Our findings demonstrate that missense mutations in MUSK can result in a severe form of CMS and indicate that the inability of MuSK mutants to interact with Dok-7, but not with Lrp4 or Tid1, is a major determinant of the pathogenesis of the CMS caused by MUSK mutations