CBS-derived H2S increases the fitness of Vibrio cholerae in host against oxidative stress by stimulating enzymatic antioxidants
Ontology highlight
ABSTRACT:
ORGANISM(S): Vibrio Cholerae O1 Str. C6706
SUBMITTER: 
Xiaoyun Liu
PROVIDER: PXD023949 | iProX | Wed Feb 03 00:00:00 GMT 2021
REPOSITORIES: iProX
Similar Datasets
Project description:Like other functional RNAs, ribozymes contain a conserved catalytic center supported by peripheral domains that vary among ribozyme sub-families. To understand how core-peripheral interactions contribute to ribozyme fitness, we compared the cleavage kinetics of all single base substitutions at 152 sites across the Bacillus subtilis glmS ribozyme by high-throughput sequencing (ClvSeq). The in vitro activity map mirrored phylogenetic sequence conservation in glmS ribozymes, indicating that biological fitness reports all biochemically important positions. Most deleterious mutations impaired RNA self-assembly. All-atom MD simulations of the complete ribozyme revealed how individual mutations in the core or the IL4 peripheral loop rewire the network of hydrogen bonds around the catalytic site. Remarkably, IL4 mutations introduce a non-native helix interface that corrupts folding of the wild type core, eliminating activity. The results illustrate how competition between native and non-native structures in RNA drives the natural selection of central and peripheral tertiary interaction motifs.
2024-09-30 | GSE261357 | GEO
Project description:Selfish genetic elements can promote their transmission at the expense of individual survival, creating conflict between the element and the rest of the genome. Recently, a large number of toxin-antidote (TA) post-segregation distorters have been identified in non-obligate outcrossing nematodes. Their origin and the evolutionary forces that keep them at intermediate population frequencies are poorly understood. Here, we study a TA element in Caenorhabditis elegans called zeel-1;peel-1. Two major haplotypes of this locus, with and without the selfish element, segregate in C. elegans. We evaluate the fitness consequences of the zeel-1;peel-1 element outside of its role in gene drive in non-outcrossing animals and demonstrate that loss of the toxin peel-1 decreased fitness of hermaphrodites and resulted in reductions in fecundity and body size. These findings suggest a biological role for peel-1 beyond toxin lethality. This work demonstrates that a TA element can provide a fitness benefit to its hosts either during their initial evolution or by being co-opted by the animals following their selfish spread. These findings guide our understanding on how TA elements can remain in a population where gene drive is minimized, helping resolve the mystery of prevalent TA elements in selfing animals.
| S-EPMC10629817 | biostudies-literature
Project description:The involvement of Mycobacterium type III-A CRISPR-Cas system in oxidative stress and intracellular fitness
| PRJNA699439 | ENA
Project description:The post-translational modification S-Sulfenylation functions as a key sensor of oxidative stress yet the dynamics of sulfenic acids in proteins is largely elusive due to it's fleeting nature. LC-MS/MS analysis has detected the evolution of this modification in oxidative and reducing states.
2016-12-23 | PXD004514 | Pride
Project description:The rates of obesity and sedentary lifestyle are on a dramatic incline, with associated detrimental health effects among women in particular. Although exercise prescriptions are useful for overcoming these problems, success can be hampered by differential responsiveness among individuals in cardiovascular fitness indices (i.e., improvements in strength, lipids, VO2max). Genetic factors appear to play an important role in determining this inter-individual variation in responsiveness. We performed microarray analyses on mRNA in whole blood from 60 sedentary women from a multi-ethnic cohort who underwent 12 weeks of exercise, to identify gene subsets that were differentially expressed between individuals who experienced the greatest and least improvements in fitness based upon a composite fitness score index. We identified 43 transcripts in 39 unique genes (FDR<10%; FC>1.5) whose expression increased the most in “high” versus “low” premenopausal female responders. Several (TIGD7, UQCRH, PSMA6, WDR12, TFB2M, USP15) have reported associations with fitness-related phenotypes. Bioinformatic analysis of the 39 genes identified 4 miRNAs whose expression has been linked to cardiovascular diseases (ANKRD22: miR-637, LRRFIP1: miR-132, PRKAR2B: miR-92a, RSAD2:miR-192). These 39 genes were enriched in 6 biological pathways, including the oxidative phosphorylation pathway (p=8.08 x 10-3). Two genes, LRRFIP1 and SNORD30, were also identified with lower expression in high responding postmenopausal women. In summary, we identified gene signatures based on mRNA analysis that define responsiveness to exercise in a largely minority-based female cohort. Importantly, this study validates several genes/pathways previously associated with exercise responsiveness and extends these findings with additional novel genes. We performed microarray analyses on mRNA in whole blood from 60 sedentary women from a multi-ethnic cohort who underwent 12 weeks of exercise, to identify gene subsets that were differentially expressed between individuals who experienced the greatest and least improvements in fitness based upon a composite fitness score index.
2012-05-31 | E-GEOD-34788 | biostudies-arrayexpress
Project description:Oxidative DNA damage is recognised by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1), initiating repair. Here, we describe a small molecule (TH10785) that interacts with the Phe319 and Gly42 amino acids of OGG1, increases the enzyme activity 10-fold and generates a novel β,δ-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and ageing.
2022-06-24 | GSE188779 | GEO
Project description:Outer membrane vesicles (OMV) are critical elements in many host-cell/microbe interactions. Previous studies of the symbiotic association between Euprymna scolopes and Vibrio fischeri had shown that within 12 h of colonizing crypts deep within the squid's light organ, the symbionts trigger an irreversible programme of tissue development in the host. Here, we report that OMV produced by V. fischeri are powerful contributors to this process. The first detectable host response to the OMV is an increased trafficking of macrophage-like cells called haemocytes into surface epithelial tissues. We showed that exposing the squid to other Vibrio species fails to induce this trafficking; however, addition of a high concentration of their OMV, which can diffuse into the crypts, does. We also provide evidence that tracheal cytotoxin released by the symbionts, which can induce haemocyte trafficking, is not part of the OMV cargo, suggesting two distinct mechanisms to induce the same morphogenesis event. By manipulating the timing and localization of OMV signal delivery, we showed that haemocyte trafficking is fully induced only when V. fischeri, the sole species able to reach and grow in the crypts, succeeds in establishing a sustained colonization. Further, our data suggest that the host's detection of OMV serves as a symbiotic checkpoint prior to inducing irreversible morphogenesis.
| S-EPMC4803540 | biostudies-literature
Project description:Horizontal gene transfer is a major force in bacterial evolution. Mobile genetic elements are responsible for much of horizontal gene transfer and also carry beneficial cargo genes. Uncovering strategies used by mobile genetic elements to benefit host cells is crucial for understanding their stability and spread in populations. We describe a benefit that ICEBs1, an integrative and conjugative element of Bacillus subtilis, provides to its host cells. Activation of ICEBs1 conferred a frequency-dependent selective advantage to host cells during two different developmental processes: biofilm formation and sporulation. These benefits were due to inhibition of biofilm-associated gene expression and delayed sporulation by ICEBs1-containing cells, enabling them to exploit their neighbors and grow more prior to development. A single ICEBs1 gene, devI (formerly ydcO), was both necessary and sufficient for inhibition of development. Manipulation of host developmental programs allows ICEBs1 to increase host fitness, thereby increasing propagation of the element.
| S-EPMC8032392 | biostudies-literature
Project description:BackgroundRecent evidence suggests that the commensal microbes act as a barrier against invading pathogens and enteric infections are the consequences of multi-layered interactions among commensals, pathogens, and the host intestinal tissue. However, it remains unclear how perturbations of the gut microbiota compromise host infection resistance, especially through changes at species and metabolite levels.ResultsHere, we illustrate how Bacteroides vulgatus, a dominant species of the Bacteroidetes phylum in mouse intestine, suppresses infection by Vibrio cholerae, an important human pathogen. Clindamycin (CL) is an antibiotic that selectively kills anaerobic bacteria, and accordingly Bacteroidetes are completely eradicated from CL-treated mouse intestines. The Bacteroidetes-depleted adult mice developed severe cholera-like symptoms, when infected with V. cholerae. Germ-free mice mono-associated with B. vulgatus became resistant to V. cholerae infection. Levels of V. cholerae growth-inhibitory metabolites including short-chain fatty acids plummeted upon CL treatment, while levels of compounds that enhance V. cholerae proliferation were elevated. Furthermore, the intestinal colonization process of V. cholerae was well-simulated in CL-treated adult mice.ConclusionsOverall, we provide insights into how a symbiotic microbe and a pathogenic intruder interact inside host intestine. We identified B. vulgatus as an indigenous microbial species that can suppress intestinal infection. Our results also demonstrate that commensal-derived metabolites are a critical determinant for host resistance against V. cholerae infection, and that CL pretreatment of adult mice generates a simple yet useful model of cholera infection.
| S-EPMC6744661 | biostudies-literature
Project description:Bacterial pathogens are highly adaptable organisms, a quality that enables them to overcome changing hostile environments. For example, Vibrio cholerae, the causative agent of cholera, is able to colonize host small intestines and combat host-produced reactive oxygen species (ROS) during infection. To dissect the molecular mechanisms utilized by V. cholerae to overcome ROS in vivo, we performed a whole-genome transposon sequencing analysis (Tn-seq) by comparing gene requirements for colonization using adult mice with and without the treatment of the antioxidant, N-acetyl cysteine. We found that mutants of the methyl-directed mismatch repair (MMR) system, such as MutS, displayed significant colonization advantages in untreated, ROS-rich mice, but not in NAC-treated mice. Further analyses suggest that the accumulation of both catalase-overproducing mutants and rugose colony variants in NAC- mice was the leading cause of mutS mutant enrichment caused by oxidative stress during infection. We also found that rugose variants could revert back to smooth colonies upon aerobic, in vitro culture. Additionally, the mutation rate of wildtype colonized in NAC- mice was significantly higher than that in NAC+ mice. Taken together, these findings support a paradigm in which V. cholerae employs a temporal adaptive strategy to battle ROS during infection, resulting in enriched phenotypes. Moreover, ΔmutS passage and complementation can be used to model hypermuation in diverse pathogens to identify novel stress resistance mechanisms.
| S-EPMC6226196 | biostudies-literature