Biology subjects

Urs, K.

Publications and source records attributed to Urs, K..

3 recordsLinked to original sources

bioRxiv2023

Nitrogen-limitation independent control of glnA (glutamine synthetase) expression in Escherichia coli by urea, several amino acids, and post-transcriptional regulation.

The expression of glnA (ammonia-assimilating glutamine synthetase) is high for uropathogenic E. coli grown in urine. Because glnA is part of an operon that codes for regulators of the nitrogen-regulated (Ntr) response, high glnA expression has been interpreted to suggest nitrogen limitation, which is unexpected because of the high urinary ammonia concentration and the extremely rapid bacterial growth. We present evidence that glnA expression does not result from nitrogen limitation. First, in the presence of ammonia, urea induced expression of glnA from the cAMP receptor protein (Crp)- dependent glnAp1 promoter, which circumvents control from the nitrogen-regulated glnAp2 promoter. This urea effect on glnA expression has not been previously described. Second, the most abundant amino acids in urine inhibited GS activity, based on reversal of the inhibition by glutamate and glutamine, and increased glnA expression. The relevance of these inhibitory amino acids in natural environments has not been previously demonstrated. Third, neither urea nor the inhibitory amino acids induced other Ntr genes, i.e., high glnA expression can be independent of other Ntr genes. Finally, the urea-dependent induction did not result in GlnA synthesis because of a previously undescribed translational control. We conclude that glnA expression in urea-containing environments does not imply growth rate-limiting nitrogen restriction and is consistent with rapid growth of uropathogenic E. coli. SignificanceUrinary tract infections (UTIs), often caused by E. coli, frequently become resistant to antibiotic treatment. Expressed metabolic genes during an infection could guide development of urgently-needed alternate or adjunct therapies. glnA (glutamine synthetase) is expressed during growth in urine, which implies growth-restricting nitrogen limitation. We show that glnA expression results from urinary amino acids that inhibit GlnA activity and urea, but not from nitrogen limitation. Urinary components will vary greatly between individuals which suggests corresponding variations in glnA expression. GlnA may be a metabolic vulnerability during UTIs, which may depend on a variable urinary composition. glnA expression may be important in a complex host-pathogen interaction, but may not be a good therapeutic target.

physiology↗

bioRxiv2021

Phenotypic and genomic diversification in complex carbohydrate degrading human gut bacteria

Symbiotic bacteria are responsible for the majority of complex carbohydrate digestion in the human colon. Since the identities and amounts of dietary polysaccharides directly impact the gut microbiota, determining which microorganisms consume specific nutrients is central to defining the relationship between diet and gut microbial ecology. Using a custom phenotyping array, we determined carbohydrate utilization profiles for 354 members of the Bacteroidetes, a dominant saccharolytic phylum. There was wide variation in the numbers and types of substrates degraded by individual bacteria, but phenotype-based clustering grouped members of the same species indicating that each species performs characteristic roles. The ability to utilize dietary polysaccharides and endogenous mucin glycans was negatively correlated, suggesting exclusion between these niches. By analyzing related Bacteroides ovatus/xylanisolvens strains that vary in their ability to utilize mucin glycans, we addressed whether gene clusters that confer this complex, multi-locus trait are being gained or lost in individual strains. Pangenome reconstruction of these strains revealed a remarkably mosaic architecture in which genes involved in polysaccharide metabolism are highly variable and bioinformatics data provide evidence of interspecies gene transfer that might explain this genomic heterogeneity. Global transcriptomic analyses suggest that the ability to utilize mucin has been lost in some lineages of B. ovatus and B. xylanisolvens, which still harbor residual gene clusters that are involved in mucin utilization by strains that still actively express this phenotype. Our data provide insight into the breadth and complexity of carbohydrate metabolism in the microbiome and the underlying genomic events that shape these behaviors.

microbiology↗

bioRxiv2020

Extensive transfer of genes for edible seaweed digestion from marine to human gut bacteria

Humans harbor numerous species of colonic bacteria that digest the fiber polysaccharides in commonly consumed terrestrial plants. More recently in history, regional populations have consumed edible macroalgae seaweeds containing unique polysaccharides. It remains unclear how extensively gut bacteria have adapted to digest these nutrients and use these abilities to colonize microbiomes around the world, especially outside Asia. Here, we show that the ability of gut bacteria to digest seaweed polysaccharides is more pervasive than previously appreciated. Using culture-based approaches, we show that known Bacteroides genes involved in seaweed degradation have mobilized into many members of this genus. We also identify several previously unknown examples of marine bacteria-derived genes, and their corresponding mobile DNA elements, that are involved in degrading seaweed polysaccharides. Some of these genes reside in gut-resident, Gram-positive Firmicutes, for which phylogenetic analysis suggests an origin in the Epulopiscium gut symbionts of marine fishes. Our results are important for understanding the metabolic plasticity of the human gut microbiome, the global exchange of genes in the context of dietary selective pressures and identifying new functions that can be introduced or engineered to design and fill orthogonal niches for a future generation of engineered probiotics.

microbiology↗