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The proteomic response of Clostridioides difficile to the Chlorotonil A derivative ChtB1-Epo2

ABSTRACT: The anaerobic, spore-forming pathogen Clostridioides difficile infects the gastrointestinal tract of higher mammals, including humans, and is the major causative agent of antibiotic-associated diarrhea. Moreover, recurrence and re-infection rates after a first successful antibiotic therapy are substantially high. To overcome the problem of recurrence and re-infection new antibiotics are urgently required that are more selective for the pathogen but spare other members of the microbiota. In turn, the microbial community inside the intestine is allowed to recover and to re-establish colonization resistance to protect against recurrence. The data presented here aim at analyzing the ability of the macrolide compound chlorotonil A to meet the requirements of C. difficile specific drug.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Peptoclostridium Difficile (strain 630) (clostridium Difficile)

SUBMITTER: Daniela Zuehlke

LAB HEAD: Susanne Sievers

PROVIDER: PXD029243 | Pride | 2023-03-29

REPOSITORIES: Pride

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			Action	DRS
	210401_HF2_DZ_MB_B1_1-5.raw	Raw
	210401_HF2_DZ_MB_B1_2-6.raw	Raw
	210401_HF2_DZ_MB_B1_3-7.raw	Raw
	210401_HF2_DZ_MB_B1_4-8.raw	Raw
	210401_HF2_DZ_MB_D1_1-5.raw	Raw

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Project description:Background: Low birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intrauterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. In a unique cohort of 17 monozygotic (MZ) monochorionic female twins very discordant for birth weight (relative differences ranging from 21.3-35.7%), we examined if adverse prenatal growth conditions experienced by the smaller co-twins lead to systemic long-lasting DNA methylation changes. Genome-wide DNA methylation profiles were acquired from saliva DNA using the Infinium HumanMethylation450 BeadChip, targeting ~2% of all CpGs in the genome. Results: Overall, co-twins showed very similar genome-wide DNA methylation profiles. Since observed differences were almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3153 were differentially methylated between the heavy and light co-twins at nominal significance (p<0.01), of which 45 showed absolute mean β-value differences >0.05 (max=0.08). Deep bisulfite sequencing of eight such loci revealed that differences remained in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicated no significant intra-pair differences. Conclusions: Severe intrauterine growth differences observed within these MZ twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies. DNA methylation profiles of saliva from 17 Adult Female MZ MC Twins discordant for birth weight.

Dataset Information

The proteomic response of Clostridioides difficile to the Chlorotonil A derivative ChtB1-Epo2

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