Biology subjects

Fenske, G.

Publications and source records attributed to Fenske, G..

2 recordsLinked to original sources

bioRxiv2019

Identifying Clostridioides difficile-inhibiting gut commensals using culturomics, phenotyping, and combinatorial community assembly

A major function of the gut microbiota is to provide colonization resistance, wherein pathogens are inhibited or suppressed below infectious level. However, the fraction of gut microbiota required for colonization resistance remains unclear. We used culturomics to isolate a gut microbiota culture collection comprising 1590 isolates belonging to 102 species. Estimated by metagenomic sequencing of fecal samples used for culture, this culture collection represents 50.73% of taxonomic diversity and 70% functional capacity. Using whole genome sequencing we characterized species representatives from this collection, and predicted their phenotypic traits, further characterizing isolates by defining nutrient utilization profile and short chain fatty acid (SCFA) production. When screened using a co-culture assay, 66 species in our culture collection inhibited C. difficile. Several phenotypes, particularly, growth rate, production of SCFAs, and the utilization of mannitol, sorbitol or succinate correlated with C. difficile inhibition. We used a combinatorial community assembly approach to formulate defined bacterial mixes inhibitory to C. difficile. When 256 combinations were tested, we found both species composition and blend size to be important in inhibition. Our results show that the interaction of bacteria with each other in a mix and with other members of gut commensals must be investigated for designing defined bacterial mixes for inhibiting C. difficile in vivo.\n\nIMPORTANCEAntibiotic treatment causes instability of gut microbiota and the loss of colonization resistance, allowing pathogens such as C. difficile to colonize, causing recurrent infection and mortality. Although fecal microbiome transplantation has shown to be an effective treatment for C. difficile infection (CDI), a more desirable approach would be the use of a defined mix of inhibitory gut bacteria. C. difficile-inhibiting species and bacterial combinations we identify herein improve our understanding of the ecological interactions controlling colonization resistance against C. difficile, and could aid the design of defined bacteriotherapy as a non-antibiotic alternative against CDI.

microbiology↗

bioRxiv2019

Geography Shapes the Population Genomics of Salmonella enterica Dublin

Salmonella enterica serotype Dublin (S. Dublin) is a bovine-adapted serotype that can cause serious systemic infections in humans. Despite the increasing prevalence of human infections and the negative impact on agricultural processes, little is known about the population structure of the serotype. To this end, we compiled a manually curated dataset comprising of 880 S. Dublin genomes. Core genome phylogeny and ancestral state reconstruction revealed that region-specific clades dominate the global population structure of S. Dublin. Strains of S. Dublin in the UK are genomically distinct from US, Brazilian and African strains. The geographical partitioning impacts the composition of the core genome as well as the ancillary genome. Antibiotic resistance genes are almost exclusively found in US genomes and is mediated by an IncA/C2 plasmid. Phage content and the S. Dublin virulence plasmid were strongly conserved in the serotype. Comparison of S. Dublin to a closely related serotype, Salmonella enterica serotype Enteritidis, revealed that S. Dublin contains 82 serotype specific genes that are not found in S. Enteritidis. Said genes encode metabolic functions involved in the uptake and catabolism of carbohydrates and virulence genes associated with type VI secretion systems and fimbria assembly respectively.\n\nIMPORTANCES. Dublin is a bovine-adapted strain that can also cause human infections. Typical S. Dublin human infections are characterized by invasion of tissue that ultimately traverses to the bloodstream causing life-threatening systemic cases. The preferred course of treatment for such infection is the administration of antibiotics. Thus, it is important to study the population structure of the serotype to monitor and identify which strains present the greatest threats to public health. Consequently, in this work, it was found that S. Dublin genomic features are greatly influenced by the region in which they populate. Our analysis found that most S. Dublin isolates from the US are distinct and have gained multidrug resistance through a new hybrid plasmid. Thus, it would be expected that infections in the US would respond less favorably to the first line of therapy and the region acts as the major source of a multidrug-resistant S. Dublin.

genomics↗