Dysregulation of cell envelope homeostasis in Staphylococcus aureus exposed to solvated lignin
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA817347 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18361157_1.fastq.gz | Fastqsanger.gz | |||
| SRR18361157_2.fastq.gz | Fastqsanger.gz | |||
| SRR18361158_1.fastq.gz | Fastqsanger.gz | |||
| SRR18361158_2.fastq.gz | Fastqsanger.gz | |||
| SRR18361159_1.fastq.gz | Fastqsanger.gz |
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Project description:Lignin is an aromatic plant cell wall polymer that facilitates water transport through the vasculature of plants. Although lignin’s ability to reduce bacterial growth been previously reported, it’s hydrophobicity complicates the ability to examine its biological effects on living cells in aqueous growth media. We recently described the ability to solvate lignin in Good’s buffers with neutral pH, a breakthrough that has allowed examination of lignin’s antimicrobial effects against the human pathogen Staphylococcus aureus. We previously showed that lignin damages the S. aureus cell membrane, causes increased cell clustering, and inhibits growth synergistically with tunicamycin, a teichoic acid synthesis inhibitor. In this current study, additional experiments were performed to better understand the physiological and transcriptomic responses of S. aureus to lignin. Intriguingly, lignin restored the susceptibility of genetically resistant S. aureus isolates to β-lactam antibiotics, dysregulated intracellular pH, and impaired normal cell division. Additionally, RNAseq analysis of lignin-treated cultures revealed a number of gene expression changes related to cell envelope, cell wall physiology, fatty acid metabolism and stress resistance. Altogether, these results represent the first comprehensive analysis of lignin’s antibacterial activity against S. aureus that provide clarity in deciphering the mechanisms of lignin’s antibacterial activity, while supporting the notion that lignin has potential to be repurposed for biomedical applications.
2022-07-12 | GSE198912 | GEO
Project description:Lignin is an aromatic plant cell wall polymer that facilitates water transport through the vasculature of plants and is generated in large quantities as an inexpensive by-product of pulp and paper manufacturing and biorefineries. Although lignin's ability to reduce bacterial growth has been reported previously, its hydrophobicity complicates the ability to examine its biological effects on living cells in aqueous growth media. We recently described the ability to solvate lignin in Good's buffers with neutral pH, a breakthrough that allowed examination of lignin's antimicrobial effects against the human pathogen Staphylococcus aureus. These analyses showed that lignin damages the S. aureus cell membrane, causes increased cell clustering, and inhibits growth synergistically with tunicamycin, a teichoic acid synthesis inhibitor. In the present study, we examined the physiological and transcriptomic responses of S. aureus to lignin. Intriguingly, lignin restored the susceptibility of genetically resistant S. aureus isolates to penicillin and oxacillin, decreased intracellular pH, impaired normal cell division, and rendered cells more resistant to detergent-induced lysis. Additionally, transcriptome sequencing (RNA-Seq) differential expression (DE) analysis of lignin-treated cultures revealed significant gene expression changes (P < 0.05 with 5% false discovery rate [FDR]) related to the cell envelope, cell wall physiology, fatty acid metabolism, and stress resistance. Moreover, a pattern of concurrent up- and downregulation of genes within biochemical pathways involved in transmembrane transport and cell wall physiology was observed, which likely reflects an attempt to tolerate or compensate for lignin-induced damage. Together, these results represent the first comprehensive analysis of lignin's antibacterial activity against S. aureus. IMPORTANCE S. aureus is a leading cause of skin and soft tissue infections. The ability of S. aureus to acquire genetic resistance to antibiotics further compounds its ability to cause life-threatening infections. While the historical response to antibiotic resistance has been to develop new antibiotics, bacterial pathogens are notorious for rapidly acquiring genetic resistance mechanisms. As such, the development of adjuvants represents a viable way of extending the life span of current antibiotics to which pathogens may already be resistant. Here, we describe the phenotypic and transcriptomic response of S. aureus to treatment with lignin. Our results demonstrate that lignin extracted from sugarcane and sorghum bagasse restores S. aureus susceptibility to β-lactams, providing a premise for repurposing these antibiotics in treatment of resistant S. aureus strains, possibly in the form of topical lignin/β-lactam formulations.
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Project description:Lignin is a universal waste product of the agricultural industry and is currently seen as a potential feedstock for more sustainable manufacturing. While it is the second most abundant biopolymer in the world, most of it is currently burned as it is a very recalcitrant material. Many recent studies, however, have demonstrated the viability of biocatalysis to improve the value of this feedstock and convert it into more useful chemicals, such as polyhydroxybutyrate, and clean fuels like hydrogen and n-butanol. Rhodopseudomonas palustris is a gram-negative bacterium which demonstrates a plethora of desirable metabolic capabilities, including aromatic catabolism useful for lignin degradation. This study uses a multi-omics approach, including the first usage of CRISPRi in R. palustris, to investigate the lignin consumption mechanisms of R. palustris, the essentiality of redox homeostasis to lignin consumption, elucidate a potential lignin catabolic superpathway, and enable more economically viable sustainable lignin valorization processes.
2025-08-25 | PXD060837 | Pride
Project description:Lignin is a biopolymer found in plant cell walls that accounts for 30% of the organic carbon in the biosphere. White-rot fungi (WRF) are considered the most efficient organisms at degrading lignin in Nature. While lignin depolymerization by WRF has been exhaustively studied, the possibility that WRF are able to utilize lignin as a carbon source is still a matter of controversy. Here we employ 13C-labeling and systems biology approaches to demonstrate that two WRF, Trametes versicolor and Gelatoporia subvermispora, funnel lignin-derived aromatic compounds into central carbon metabolism via intracellular catabolic pathways. These results provide insights into global carbon cycling in soil ecosystems, and furthermore establishes a foundation for employing WRF in simultaneous lignin depolymerization and bioconversion to bioproducts – a key step towards enabling a sustainable bioeconomy.
2021-01-15 | GSE151629 | GEO
Project description:Lignin, a recalcitrant aromatic biopolymer, represents a promising feedstock for sustainable biorefining. In this study, we characterized the transcriptional response of the fungus Curvularia clavata J1 to alkali lignin (AL) and developed a Cu2+-inducible MCM5–AID base editing system for genome-wide C-to-T and G-to-A mutagenesis. Transcriptomic analysis revealed that AL exposure triggered upregulation of genes involved in electron transport, lipid catabolism, and iron homeostasis. Using droplet microfluidics, we conducted ultrahigh-throughput screening and identified a mutant strain, M6, exhibiting superior phenotypic traits. When cultivated in lignosulfonate medium, M6 showed a 33–36% increase in lipid production and a 75–87% enhancement in laccase activity. Transcriptional profiling further indicated reinforced metabolic pathways related to fatty acid, steroid, and glycerolipid biosynthesis, redirecting carbon flux toward the formation of oil-enriched single-cell protein. This study establishes an integrated platform for lignin valorization and underscores the synergy between synthetic biology and microfluidics for precision engineering of fungal hosts.
2025-08-28 | GSE306066 | GEO
Project description:Molecular interplay between peptidoglycan integrity and outer membrane asymmetry in maintaining cell envelope homeostasis
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Project description:<p>We identified germline heterozygous mutations in <i>CTLA4</i> in members of four families with severe immune dysregulation. Human <i>CTLA4</i> haploinsufficiency caused dysregulation of FoxP3+ regulatory T (Treg) cells and lymphocytic infiltration of target organs, mimicking <i>Ctla4</i> homozygous mice. Patients also exhibited a B cell phenotype, with progressive loss of B cells and accumulation of autoreactive CD21<sup>lo</sup> B cells. This study demonstrates a critical quantitative role for CTLA-4 in human immune homeostasis.</p>
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Project description:Dysregulation of protein homeostasis by mutant UBA1 in VEXAS syndrome [WES]
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Project description:This study aims to reveal genes related to lignin production in Cenchrus purpureus through RNA-Seq. This species is widely used as forrage for cattle, and for the last years, due to its high biomass yield, has been considered as source to lignocellulosic ethanol. Given those two importances, lignin is a molecule related to low digestibility in cattle and recalcitrance in biofuel production. Eight samples were chosen from previous lignin production and forage quality data; four samples had low lignin production, and four had high lignin production. The highest nodes were collected for RNA extraction using TRIzol reagent, following Jordon-Thaden et a;. (2015) protocol. The cDNA library preparation was generated according to Illumina TruSeq Stranded mRNA Sample Prep kit protocol, and RNA sequencing was performed using HiSeq 2500 sequencer. Quality control was measured by FastQC software v 0.11.8. The sequenced reads were aligned to Cenchrus purpureus genome through STAR software v. 2.5.2b (Dobin et al., 2012). After that, the transcriptome was assembled using Stringtie v 2.0.4 software (Pertea et al., 2015). Salmon v 0.7.2 software (Patro et al., 2017) was used to quantify the sequenced reads. The DEG was identified using DESeq2 package, and genes functions were annotated through Trinotate software (Bryant et al., 2017). In total, approximately 130 million reads were sequenced. The final assembled transcriptome was formed by 101,169 transcripts. The differential expressed genes analysis revealed 52 significatively genes. Here, we highlighted genes related to sterol, L-serine and terpene biosynthetic process.
2021-10-01 | GSE174718 | GEO