Biology subjects

Sauer, U.

Publications and source records attributed to Sauer, U..

4 recordsLinked to original sources

bioRxiv2018

Synthesis and degradation of FtsZ determines the first cell division in starved bacteria

In natural environments, microbes are typically non-dividing. Such quiescent cells manage fleeting nutrients and gauge when intra- and extracellular resources permit division. Quantitative prediction of the division event as a function of nutritional status is currently achieved through phenomenological models for nutrient-rich, exponentially growing cultures. Such models, however, cannot predict the first division of cells under limiting nutrient availability. To address this, we analyzed the metabolic capability of starved Escherichia coli that were fed pulsed glucose at defined frequencies. Real-time metabolomics and microfluidic single-cell microscopy revealed unexpected, rapid protein and nucleic acid synthesis already in non-dividing cells. Additionally, the lag time to first division shortened as pulsing frequency increased. Here, we demonstrate that the first division from a non-dividing state occurs when the facilitating protein FtsZ reaches division-supporting concentration. A dynamic model quantitatively relates lag time to FtsZ synthesis from nutrient pulses and its protease-dependent degradation. Consistent with model predictions, lag time shortened when FtsZ synthesis was supplemented or protease inhibitors were added. Lag time prolonged when ftsZ was repressed or FtsZ degradation rate was increased. Thus, we provide a basis to quantitatively predict bacterial division using information about molecular determinants and the nutrient input.

microbiology↗

bioRxiv2018

Two parallel pathways implement robust propionate catabolism and detoxification in mycobacteria

Tuberculosis remains a major global health threat with over 1.5 million deaths each year. Mycobacterium tuberculosis success story is related to a flexible metabolism, allowing growth despite restrictive conditions within the human host.\n\nHost lipids stores are a major carbon source in vivo. Their catabolism yields propionyl-CoA, which is processed by two parallel pathways, the methylmalonyl CoA pathway and the methylcitrate pathway. Both pathways are considered potential drug targets. The methylcitrate pathway is upregulated in the pathological context. However, intermediates of this pathway can be cytotoxic and Mtbs preference for its usage remains unclear.\n\nWe combine thermodynamic kinetic modeling, quantitative proteomics and time-resolved metabolomics to characterize the interplay between the two pathways and to show their functionalities in an efficient and fast propionate catabolism.\n\nWe find that the methylcitrate pathway acts as a transcriptionally regulated, high capacity catabolic pathway due to its favorable thermodynamics and metabolic control distribution. In contrast, the methylmalonyl pathway is constitutively fulfilling biosynthetic tasks and can quickly detoxify propionate pulses, but is thermodynamically restricted to lower capacity.

systems biology↗

bioRxiv2017

Antibodies set boundaries limiting microbial metabolite penetration and the resultant mammalian host response

Although the mammalian microbiota is well-contained within the intestine and on other body surfaces, it profoundly shapes development and metabolism of almost every host organ, presumably through pervasive microbial metabolite penetration. The challenge is that most metabolites can be of both host and microbial origin. We developed a model to distinguish between microbial and host metabolites by stable isotope tracing using fully 13C-labelled live non-replicating Escherichia coli, differentiating 12C and 13C isotopes with high-resolution mass spectrometry. Hundreds of microbial compounds penetrated across 23 host tissues and fluids after intestinal exposure: subsequent 12C host metabolome signatures included lipidemia, reduced glycolysis and inflammation. Mucosal barrier maturation with transient microbial exposure increased early clearance of penetrant bacterial metabolites from the small intestine into the urine, independently of antibody induction. Induced antibodies curtailed microbial metabolite exposure at the intestinal surface, by accelerating intestinal bacterial transit into the colon where metabolite transport mechanisms are limiting.

immunology↗

bioRxiv2017

Disentangling metabolic functions of bacteria in the honey bee gut

It is presently unclear how much individual community members contribute to the overall metabolic output of a gut microbiota. To address this question, we used the honey bee, which harbors a relatively simple and remarkably conserved gut microbiota with striking parallels to the mammalian system and importance for bee health. Using untargeted metabolomics, we profiled metabolic changes in gnotobiotic bees that were colonized with the complete microbiota reconstituted from cultured strains. We then determined the contribution of individual community members in mono-colonized bees, and recapitulated our findings using in vitro cultures. Our results show that the honey bee gut microbiota utilizes a wide range of pollen-derived substrates including flavonoids and outer pollen wall components, suggesting a key role for degradation of recalcitrant secondary plant metabolites and pollen digestion. In turn, multiple species were responsible for the accumulation of organic acids and polyphenol degradation products, and a specific gut symbiont, Bifidobacterium asteroides, stimulated the production of host hormones known to impact bee development. While we found evidence for cross-feeding interactions, [~]80% of the identified metabolic changes were also observed in mono-colonized bees with Lactobacilli being responsible for the largest share of the metabolic output. These results suggest that bacteria in the honey bee gut colonize largely independent metabolic niches, which may be a general characteristic of gut microbiomes. Our study reveals diverse metabolic functions of gut bacteria that are likely to contribute to bee health, and provide fundamental insights into how metabolic functions are partitioned within gut communities.\n\nAuthor summaryHoney bees are important pollinators that harbor a simple gut microbiota with striking parallels to the mammalian system. This makes them relevant models to study gut microbiota functions and its impact on host health. We applied untargeted metabolomics to characterize metabolic changes induced by the gut microbiota, and to characterize contributions of the major community members. We find that the gut microbiota digests recalcitrant substrates derived from the bees pollen-diet. Most metabolic changes could be explained by the activity of individual community members suggesting substrate specificity and independent metabolic niches. Our study provides novel insights into the functional understanding of the bee gut microbiota and provides a framework for applying untargeted metabolomics to disentangle metabolic functions of gut bacteria.

microbiology↗