Biology subjects

van Kessel, S. P.

Publications and source records attributed to van Kessel, S. P..

5 recordsLinked to original sources

bioRxiv2025

Globodera pallida virulence on major potato resistance has a common genetic basis across Western Europe

The potato cyst nematode Globodera pallida poses a major threat to potato production in Western Europe. Current management strategies largely depend on the use of potato varieties carrying the genetic resistance GpaVvrn. However, reports from multiple West-European countries indicate a steady rise in virulence against GpaVvrn-containing potato varieties, raising serious concerns about G. pallida control. Although recent studies have resolved the genetic basis of virulence in two Dutch G. pallida populations, it remains unclear how conserved this genetic adaptation is in populations from different regions. To investigate this, we first selected eight Dutch G. pallida populations on the GpaVvrn-containing potato variety Seresta and confirmed a previously identified virulence locus. Second, by analysing the allele frequencies of four virulence-associated SNPs in Dutch, British, and French GpaVvrn-selected G. pallida populations, we found that the same allele is consistently selected by GpaVvrn across Western Europe. Third, we analysed the propagation of eight G. pallida populations on 26 GpaVvrn-containing potato varieties and showed that a populations allele frequency of a single SNP (T173N) accurately reflects its reproduction on GpaVvrn. Fourth, we developed an allele-specific quantitative PCR (AS-qPCR) assay to determine a populations alternative allele frequency (AAF) of T173N and showed that AS-qPCR-based AAFs reliably indicate virulence levels on GpaVvrn in Dutch and German G. pallida populations. Together, these findings suggest that a common allele is consistently selected by GpaVvrn in populations from different regions across Western Europe. The AS-qPCR assay developed in this study provides a practical tool to estimate G. pallida virulence on GpaVvrn in the field, enabling field-tailored and sustainable resistance management strategies for farmers.

genetics↗

bioRxiv2021

Parkinson' disease medication alters rat small intestinal motility and microbiota composition

Parkinsons disease (PD) is known to be associated with altered gastrointestinal function and microbiota composition. Altered gastrointestinal function is key in the development of small intestinal bacterial overgrowth, which is a comorbidity often observed in PD patients. Although PD medication could be an important confounder in the reported alterations, its effect per se on the microbiota composition or the gastrointestinal function at the site of drug absorption has not been studied. To this end, healthy (i.e., not PD model) wild-type Groningen rats were employed and treated with dopamine, pramipexole (in combination with levodopa/carbidopa), or ropinirole (in combination with levodopa/carbidopa) for 14 sequential days. Rats treated with dopamine agonists showed a significant reduction in the small intestinal motility and an increase in bacterial overgrowth in the distal small intestine. Importantly, significant alterations in microbial taxa were observed between the treated and vehicle groups, analogous to the changes previously reported in human PD vs HC microbiota studies. These microbial changes included an increase in Lactobacillus and Bifidobacterium, and decrease in Lachnospiraceae and Prevotellaceae. Importantly, certain Lactobacillus species correlated negatively with the plasma levels of levodopa. Overall, the results highlight the significant effect of PD medication per se on the gut microbiota, and the disease-associated comorbidities, including gastrointestinal dysfunction and small intestinal bacterial overgrowth. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSIn the last years many studies focused on the faecal microbiota profiles of Parkinsons disease (PD) patients and compared them to healthy control (HC) subjects and reported a difference between the microbiota profiles. Although some bacterial taxa have been reported to be differential abundant across studies there is a low consensus between the overall changes observed. It remains to be elucidated whether and how the disease status itself, the PD medication or the gastrointestinal dysfunction, an often reported comorbidity, plays a role in the altered microbiota profiles of Parkinsons disease patients. Added value of this studyTwo major confounding factors potentially affecting the microbiota profiles differentiating PD patients from HC subjects are the PD medication and gastrointestinal dysfunction. We showed that PD medication elicits an decreasing effect on the small intestinal gut motility in a healthy (i.e. non Parkinson) rat model which was a contributing factor to the altered microbiota profile observed. We found that taxa reported previously to be differentially abundant were mirrored in our healthy rat model showing the impact of PD medication on microbiota profiles. Implications of all the available evidenceThis study showed that PD medication and gastrointestinal motility are important factors in the microbiota profiles and could explain some of the differential abundant taxa reported in the cross-sectional PD microbiota studies. Future studies should take the potential side effects of medication that could elicit alterations of the microbiota composition into account when seeking for microbial biomarkers of disease status.

microbiology↗

bioRxiv2020

Bacterial deamination of residual levodopa medication for Parkinson's disease elicits inhibitory effect on gut motility

Aromatic bacterial metabolites are attracting considerable attention due to their impact on gut homeostasis and hosts physiology. Clostridium sporogenes is a key contributor to the production of these bioactive metabolites in the human gut. Here, we show that C. sporogenes deaminates levodopa, the main treatment in Parkinsons disease, and identify the aromatic aminotransferase responsible for the initiation of the deamination pathway. The deaminated metabolite from levodopa, 3-(3,4-dihydroxyphenyl)propionic acid, elicits an inhibitory effect on ileal motility in an ex vivo model. 3-(3,4-dihydroxyphenyl)propionic acid is detected in fecal samples of Parkinsons disease patients on levodopa medication. Our data are of significant impact to the treatment of Parkinsons disease, where constipation is reported as the most common gastrointestinal symptom. Overall, this study underpins the importance of the metabolic pathways of the gut microbiome involved in drug metabolism not only to preserve drug effectiveness, but also to avoid potential side effects of bacterial breakdown products of the unabsorbed residue of medication.

microbiology↗

bioRxiv2018

Gut bacterial tyrosine decarboxylases restrict the bioavailability of levodopa, the primary treatment in Parkinson’s disease

Human gut bacteria play a critical role in the regulation of immune and metabolic systems, as well as in the function of the nervous system. The microbiota senses its environment and responds by releasing metabolites, some of which are key regulators of human health and disease. In this study, we identify and characterize gut-associated bacteria in their ability to decarboxylate L-DOPA (also known as Levodopa or L-3,4-dihydroxyphenylalanine) to dopamine via the tyrosine decarboxylases, which are mainly present in the class Bacilli. Although the bacterial tyrosine decarboxylases have a higher affinity for tyrosine compared to L-DOPA, this does not affect their ability to decarboxylate L-DOPA, nor does any inhibitor of the human decarboxylase. This study indicates that in situ bioavailability of L-DOPA is compromised by the gut bacterial tyrosine decarboxylase abundance in Parkinsons patients. Finally, we show that the tyrosine decarboxylase abundance in the microbiota at the site of L-DOPA absorption, the proximal small intestine, significantly influences L-DOPA bioavailability in the plasma of rats. Our results highlight the role of microbial metabolism in drug bioavailability, and specifically, that small intestinal abundance of bacterial tyrosine decarboxylase can explain the highly variable L-DOPA dosage regimens required in the treatment of individual Parkinsons patients.\n\nHighlightsO_LISmall intestinal bacteria is able to convert L-DOPA to dopamine\nC_LIO_LIL-DOPA metabolism by gut bacteria reduce the bioavailability of L-DOPA in the body, thus is a significant explanatory factor of the highly variable L-DOPA dosage regimens required in the treatment of individual Parkinsons patients.\nC_LIO_LIInhibitors of the human DOPA decarboxylase are not potent inhibitors for bacterial tyrosine decarboxylases\nC_LI

molecular biology↗

bioRxiv2016

High-throughput CRISPRi phenotyping in Streptococcus pneumoniae identifies new essential genes involved in cell wall synthesis and competence development

Genome-wide screens have discovered a large set of essential genes in the opportunistic human pathogen Streptococcus pneumoniae. However, the functions of many essential genes are still unknown, hampering vaccine development and drug discovery. Based on results from transposon-sequencing (Tn-Seq), we refined the list of essential genes in S. pneumoniae serotype 2 strain D39. Next, we created a knockdown library targeting 348 potentially essential genes by CRISPR interference (CRISPRi) and show a growth phenotype for 254 of them (73%). Using high-content microscopy screening, we searched for essential genes of unknown function with clear phenotypes in cell morphology upon CRISPRi-based depletion. We show that SPD1416 and SPD1417 (renamed to MurT and GatD, respectively) are essential for peptidoglycan synthesis, and that SPD1198 and SPD1197 (renamed to TarP and TarQ, respectively) are responsible for the polymerization of teichoic acid (TA) precursors. This knowledge enabled us to reconstruct the unique pneumococcal TA biosynthetic pathway. CRISPRi was also employed to unravel the role of the essential Clpproteolytic system in regulation of competence development and we show that ClpX is the essential ATPase responsible for ClpP-dependent repression of competence. The CRISPRi library provides a valuable tool for characterization of pneumococcal genes and pathways and revealed several promising antibiotic targets.

microbiology↗