Can we microbe-manage our vitamin acquisition for better health?

Nysten, Jana; Dijck, Patrick Van

doi:10.1371/journal.ppat.1011361

Cited by 5 publications

(3 citation statements)

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“…(29). However, the riboflavin concentration in the gut may be higher than in other tissues due to dietary intake and microbial vitamin production (17). Furthermore, our findings revealed unexpected dynamics in co-culture experiments where auxotrophic S. cerevisiae outcompeted auxotrophic C. albicans in lower riboflavin concentrations while this was not the case for higher concentrations or the wild-type strains.…”

Section: Discussionmentioning

confidence: 62%

“…Riboflavin, also known as vitamin B 2 is a water-soluble micronutrient crucial for the vitality of all living organisms (16). Although many bacteria, fungi, and plants can synthesize this vitamin themselves, mammals, including humans, have lost this ability and rely on external sources such as nutrition and, to a lesser extent, intestinal microorganisms (17,18). The synthesis of riboflavin in bacteria, fungi, and plants involves the conversion of one molecule of guanosine-5'-triphosphate (GTP) and two molecules of ribulose 5-phosphate by various Rib enzymes, ultimately forming riboflavin (19).…”

Section: Importance: Introductionmentioning

confidence: 99%

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The riboflavin biosynthetic pathway as a novel target for antifungal drugs againstCandidaspecies

Nysten,

Peetermans,

Vaneynde

et al. 2024

Preprint

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In recent decades, there has been an increase in the occurrence of fungal infections, yet the arsenal of drugs available to fight invasive infections remains very limited. The development of new antifungal agents is hindered by the restricted number of molecular targets that can be exploited, given the shared eukaryotic nature of fungi and their hosts which often leads to host toxicity. In this paper, we examine the riboflavin biosynthetic pathway as a potential novel drug target. Riboflavin is an essential nutrient for all living organisms. Its biosynthetic pathway does not exist in humans, who obtain riboflavin through their diet. Our findings demonstrate that all enzymes in the pathway are essential for Candida albicans, Candida glabrata, and Saccharomyces cerevisiae. Among these enzymes, Rib1 and Rib3 are the most promising targets. Auxotrophic strains, which mimic a drug targeting the biosynthesis pathway, experience rapid mortality in the absence of supplemented riboflavin. Nevertheless, the cells can still take up external riboflavin when supplemented. We identified Orf19.4337 as the riboflavin importer in C. albicans and named it Rut1. We found that Rut1 only facilitates growth at external riboflavin concentrations that exceed the physiological concentrations in the human body, making it unlikely that riboflavin uptake to act as a potential resistance mechanism for a drug targeting the biosynthesis pathway. Interestingly, the uptake system in S. cerevisiae is more effective than in C. albicans and C. glabrata, enabling an auxotrophic S. cerevisiae strain to outcompete an auxotrophic C. albicans strain in lower riboflavin concentrations.

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Section: Discussionmentioning

confidence: 62%

Section: Importance: Introductionmentioning

confidence: 99%

The riboflavin biosynthetic pathway as a novel target for antifungal drugs againstCandidaspecies

Nysten,

Peetermans,

Vaneynde

et al. 2024

Preprint

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“…In fact, the large majority is not harmful to us or to other animals or plants, but in many cases beneficial and necessary. As an example, we have formed intricate relationships with the bacteria inhabiting our gastrointestinal tract -in fact more than a trillion inhabit our digestive system (Sender et al, 2016), and some members help satisfy our vitamin needs (Nysten & Van Dijck, 2023). Today we also employ bacteria in a broad variety of processes of societal importance, such as fermentation, metal recovery, bioremediation of for example oil spills, or wastewater treatment.…”

Section: Microbiology a Short Historical Perspectivementioning

confidence: 99%

Seasonality influences gene expression in Baltic Sea microbial communities

Amnebrink

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Prokaryotes are the most abundant living organisms in the marine environment. They contribute to primary production and the recycling of its products. Collectively they influence the marine element cycles of carbon along with elements like nitrogen and sulfur. However, much remains to learn of the functional characteristics of microbial communities carrying out these processes, and how different communities respond to changing environmental conditions in space and time.The composition of marine prokaryotic communities is known to change in a seasonal manner, but how seasonality influences their gene expression or “activity” remains largely unknown. In this thesis I investigate the relationship between prokaryotic activity, relative gene expression, and seasonality using time series field data on gene expression combined with reference genomes of prokaryotic populations (metagenome assembled genomes, MAGs). This revealed pronounced seasonal succession in overall transcriptional dynamics. Importantly, roughly half of the 50 populations with highest relative abundance in transcription altered their transcriptional profiles across seasons. Thus, changes in relative gene expression on the annual scale is explained by community turnover and modulation of activity within populations. Characterization of a MAG representative of the filamentous cyanobacterial genus Aphanizomenon that forms summer blooms in the Baltic Proper, highlighted seasonal patterns in transcription of genes underlying key prokaryotic activities. This included genes related to photosynthesis (different genes expressed in different seasons), nitrogen- fixation (expression peaking in summer) and oxidative stress (peaking in winter). A mesocosm study in the Bothnian Sea using temperature and nutrient manipulations simulating the winter to summer transition showed lower growth efficiency and higher maintenance respiration in winter conditions, implying larger relative losses of CO2 through respiration in winter. Additionally, temperature, nutrients, and their combination, caused separation in both prokaryotic taxonomy and transcription of metabolic pathways. Key features included archaeal transcription of ammonium oxidation in winter conditions, and Oceanospirillales central metabolisms in summer. Taken together, these results highlight the pronounced effect of seasonality on prokaryotic community gene expression and the capability of prokaryotic populations to alter their expressed genetic repertoire. This emphasizes the importance of the temporal perspective when considering how prokaryotic communities will respond to changes in environmental conditions.

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