The treatment of infections due to the opportunistic pathogen Pseudomonas aeruginosa is often difficult, as a consequence of bacterial biofilm formation. Such a protective environment shields the bacterium from host defense and antibiotic treatment and secures its survival. One crucial factor for maintenance of the biofilm architecture is the carbohydrate-binding lectin LecB. Here, we report the identification of potent mannose-based LecB inhibitors from a screening of four series of mannosides in a novel competitive binding assay for LecB. Cinnamide and sulfonamide derivatives are inhibitors of bacterial adhesion with up to a 20-fold increase in affinity to LecB compared to the natural ligand methyl mannoside. Because many lectins of the host require terminal saccharides (e.g., fucosides), such capped structures as reported here may offer a beneficial selectivity profile for the pathogenic lectin. Both classes of compounds show distinct binding modes at the protein, offering the advantage of a simultaneous development of two new lead structures as anti-pseudomonadal drugs with an anti-virulence mode of action.
Summary Bacterial degradation of the sugar sulfoquinovose (SQ, 6-deoxy-6-sulfoglucose) produced by plants, algae, and cyanobacteria, is an important component of the biogeochemical carbon and sulfur cycles. Here, we reveal a third biochemical pathway for primary SQ degradation in an aerobic Bacillus aryabhattai strain. An isomerase converts SQ to 6-deoxy-6-sulfofructose (SF). A novel transaldolase enzyme cleaves the SF to 3-sulfolactaldehyde (SLA), while the non-sulfonated C 3 -(glycerone)-moiety is transferred to an acceptor molecule, glyceraldehyde phosphate (GAP), yielding fructose-6-phosphate (F6P). Intestinal anaerobic bacteria such as Enterococcus gilvus , Clostridium symbiosum , and Eubacterium rectale strains also express transaldolase pathway gene clusters during fermentative growth with SQ. The now three known biochemical strategies for SQ catabolism reflect adaptations to the aerobic or anaerobic lifestyle of the different bacteria. The occurrence of these pathways in intestinal (family) Enterobacteriaceae and (phylum) Firmicutes strains further highlights a potential importance of metabolism of green-diet SQ by gut microbial communities to, ultimately, hydrogen sulfide.
Ammonia released during organic matter mineralization is converted during nitrification to nitrate. We followed spatiotemporal dynamics of the nitrifying microbial community in deep oligotrophic Lake Constance. Depth-dependent decrease of total ammonium (0.01-0.84 μM) indicated the hypolimnion as the major place of nitrification with 15 N-isotope dilution measurements indicating a threefold daily turnover of hypolimnetic total ammonium. This was mirrored by a strong increase of ammonia-oxidizing Thaumarchaeota towards the hypolimnion (13%-21% of bacterioplankton) throughout spring to autumn as revealed by amplicon sequencing and quantitative polymerase chain reaction. Ammonia-oxidizing bacteria were typically two orders of magnitude less abundant and completely ammonia-oxidizing (comammox) bacteria were not detected. Both, 16S rRNA gene and amoA (encoding ammonia monooxygenase subunit B) analyses identified only one major species-level operational taxonomic unit (OTU) of Thaumarchaeota (99% of all ammonia oxidizers in the hypolimnion), which was affiliated to Nitrosopumilus spp. The relative abundance distribution of the single Thaumarchaeon strongly correlated to an equally abundant Chloroflexi clade CL500-11 OTU and a Nitrospira OTU that was one order of magnitude less abundant. The latter dominated among recognized nitrite oxidizers. This extremely low diversity of nitrifiers shows how vulnerable the ecosystem process of nitrification may be in Lake Constance as Central Europe's third largest lake.
Responses of the microbiota to diet are highly personalized but mechanistically not well understood because many metabolic capabilities and interactions of human gut microorganisms are unknown. Here we show that sulfoquinovose (SQ), a sulfonated monosaccharide omnipresent in green vegetables, is a selective yet relevant substrate for few but ubiquitous bacteria in the human gut. In human feces and in defined co-culture, Eubacterium rectale and Bilophila wadsworthia used recently identified pathways to cooperatively catabolize SQ with 2,3-dihydroxypropane-1-sulfonate as a transient intermediate to hydrogen sulfide (H2S), a key intestinal metabolite with disparate effects on host health. SQ-degradation capability is encoded in almost half of E. rectale genomes but otherwise sparsely distributed among microbial species in the human intestine. However, re-analysis of fecal metatranscriptome datasets of four human cohorts showed that SQ degradation (mostly from E. rectale and Faecalibacterium prausnitzii) and H2S production (mostly from B. wadsworthia) pathways were expressed abundantly across various health states, demonstrating that these microbial functions are core attributes of the human gut. The discovery of green-diet-derived SQ as an exclusive microbial nutrient and an additional source of H2S in the human gut highlights the role of individual dietary compounds and organosulfur metabolism on microbial activity and has implications for precision editing of the gut microbiota by dietary and prebiotic interventions.
Diet selectively shapes the human gut microbiota and fuels production of diverse metabolites that influence host health. Responses of the microbiota to diet are highly personalized, yet mechanistically not well understood because the metabolic capabilities of human gut microorganisms remain largely unknown. Here we show that sulfoquinovose (SQ), an omnipresent monosaccharide in green vegetables, is a selective substrate for few but ubiquitous bacteria in the human gut. In anoxic incubations of human feces and in defined co-culture, Eubacterium rectale and Bilophila wadsworthia both use previously unrecognized pathways to cooperatively catabolize SQ to hydrogen sulfide (H2S), a key intestinal metabolite with disparate effects on host health. We find SQ degradation capability encoded in almost half of E. rectale genomes but otherwise sparsely distributed among microbial species in the human intestine. Re-analysis of fecal metatranscriptome datasets of four human cohorts showed that SQ degradation (mostly from E. rectale and Faecalibacterium prausnitzii) and H2S production (mostly from B. wadsworthia) pathways were expressed abundantly across various health states, suggesting their active contribution to gut functioning. The discovery of green diet-derived SQ as an exclusive microbial nutrient and an additional source of H2S in the human gut highlights the role of individual dietary compounds and organosulfur metabolism on microbial activity and has implications for precision editing of the gut microbiota by dietary and prebiotic interventions.
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