Project description:Bacterial metabolites are substrates of virulence factors of uropathogenic Escherichia coli (UPEC), but the mechanism underlying the role of functional metabolites in bacterial virulence from the perspective of small molecular metabolism is unclear. In the present study, we used a strategy of functional metabolomics integrated with bacterial genetics in attempt to decipher the mechanism of virulence formation in Escherichia coli (E. coli) from the viewpoint of small molecule metabolism. We identified the virulence-associated metabolome via analysis of the primary metabolome of the pathogenic UTI89 strain and the non-pathogenic MG1655 strain. Then, the iron-mediated virulence associated metabolome was identified by an iron fishing strategy. Also, the mechanism of siderophores in regulating pathogenicity in different environments was explored by investigating the effect of iron on siderophore biosynthesis. Finally, by knocking out genes related to siderophore biosynthesis, siderophore transport and iron utilization, siderophores dependent iron-regulating virulence associated metabolome, including 18 functional metabolites, was identified and verified to be involved in the regulation of bacterial virulence. Based on this we found that these functional metabolites regulated the virulence of E. coli by targeting multiple metabolic pathways in an iron-siderophores dependent manner. Moreover, a quantitative proteomics approach was implemented to further elucidate the mechanism of functional metabolites and functional proteins in modulating bacterial virulence. And our findings demonstrated that functional proteins regulated the virulence of E. coli by mediating iron binding, iron-siderophore transmembrane transport, and the biosynthesis and expression of functional metabolites. Interestingly, we found that functional metabolites enhance the virulence of E. coli by specifically modulating the key metabolic pathways involved in purine metabolism, proline metabolism, arginine metabolism and pyrimidine metabolism. Taken together, our study identified for the first time 18 functional metabolites regulating the of E. coli virulence, greatly enriching our understanding of the mechanism of functional metabolites that regulate the E. coli virulence by targeting primary metabolism, which will largely contribute to the development of new strategies to target virulence-based diagnosis and therapy of infections caused by different pathogens.
Project description:Bacterial metabolites are substrates of virulence factors of uropathogenic Escherichia coli (UPEC), but the mechanism underlying the role of functional metabolites in bacterial virulence from the perspective of small molecular metabolism is unclear. In the present study, we used a strategy of functional metabolomics integrated with bacterial genetics in attempt to decipher the mechanism of virulence formation in Escherichia coli (E. coli) from the viewpoint of small molecule metabolism. We identified the virulence-associated metabolome via analysis of the primary metabolome of the pathogenic UTI89 strain and the non-pathogenic MG1655 strain. Then, the iron-mediated virulence associated metabolome was identified by an iron fishing strategy. Also, the mechanism of siderophores in regulating pathogenicity in different environments was explored by investigating the effect of iron on siderophore biosynthesis. Finally, by knocking out genes related to siderophore biosynthesis, siderophore transport and iron utilization, siderophores dependent iron-regulating virulence associated metabolome, including 18 functional metabolites, was identified and verified to be involved in the regulation of bacterial virulence. Based on this we found that these functional metabolites regulated the virulence of E. coli by targeting multiple metabolic pathways in an iron-siderophores dependent manner. Moreover, a quantitative proteomics approach was implemented to further elucidate the mechanism of functional metabolites and functional proteins in modulating bacterial virulence. And our findings demonstrated that functional proteins regulated the virulence of E. coli by mediating iron binding, iron-siderophore transmembrane transport, and the biosynthesis and expression of functional metabolites. Interestingly, we found that functional metabolites enhance the virulence of E. coli by specifically modulating the key metabolic pathways involved in purine metabolism, proline metabolism, arginine metabolism and pyrimidine metabolism. Taken together, our study identified for the first time 18 functional metabolites regulating the of E. coli virulence, greatly enriching our understanding of the mechanism of functional metabolites that regulate the E. coli virulence by targeting primary metabolism, which will largely contribute to the development of new strategies to target virulence-based diagnosis and therapy of infections caused by different pathogens.
Project description:Bacterial metabolites are substrates of virulence factors of uropathogenic Escherichia coli (UPEC), but the mechanism underlying the role of functional metabolites in bacterial virulence from the perspective of small molecular metabolism is unclear. In the present study, we used a strategy of functional metabolomics integrated with bacterial genetics in attempt to decipher the mechanism of virulence formation in Escherichia coli (E. coli) from the viewpoint of small molecule metabolism. We identified the virulence-associated metabolome via analysis of the primary metabolome of the pathogenic UTI89 strain and the non-pathogenic MG1655 strain. Then, the iron-mediated virulence associated metabolome was identified by an iron fishing strategy. Also, the mechanism of siderophores in regulating pathogenicity in different environments was explored by investigating the effect of iron on siderophore biosynthesis. Finally, by knocking out genes related to siderophore biosynthesis, siderophore transport and iron utilization, siderophores dependent iron-regulating virulence associated metabolome, including 18 functional metabolites, was identified and verified to be involved in the regulation of bacterial virulence. Based on this we found that these functional metabolites regulated the virulence of E. coli by targeting multiple metabolic pathways in an iron-siderophores dependent manner. Moreover, a quantitative proteomics approach was implemented to further elucidate the mechanism of functional metabolites and functional proteins in modulating bacterial virulence. And our findings demonstrated that functional proteins regulated the virulence of E. coli by mediating iron binding, iron-siderophore transmembrane transport, and the biosynthesis and expression of functional metabolites. Interestingly, we found that functional metabolites enhance the virulence of E. coli by specifically modulating the key metabolic pathways involved in purine metabolism, proline metabolism, arginine metabolism and pyrimidine metabolism. Taken together, our study identified for the first time 18 functional metabolites regulating the of E. coli virulence, greatly enriching our understanding of the mechanism of functional metabolites that regulate the E. coli virulence by targeting primary metabolism, which will largely contribute to the development of new strategies to target virulence-based diagnosis and therapy of infections caused by different pathogens.
Project description:Bacterial metabolites are substrates of virulence factors of uropathogenic Escherichia coli (UPEC), but the mechanism underlying the role of functional metabolites in bacterial virulence from the perspective of small molecular metabolism is unclear. In the present study, we used a strategy of functional metabolomics integrated with bacterial genetics in attempt to decipher the mechanism of virulence formation in Escherichia coli (E. coli) from the viewpoint of small molecule metabolism. We identified the virulence-associated metabolome via analysis of the primary metabolome of the pathogenic UTI89 strain and the non-pathogenic MG1655 strain. Then, the iron-mediated virulence associated metabolome was identified by an iron fishing strategy. Also, the mechanism of siderophores in regulating pathogenicity in different environments was explored by investigating the effect of iron on siderophore biosynthesis. Finally, by knocking out genes related to siderophore biosynthesis, siderophore transport and iron utilization, siderophores dependent iron-regulating virulence associated metabolome, including 18 functional metabolites, was identified and verified to be involved in the regulation of bacterial virulence. Based on this we found that these functional metabolites regulated the virulence of E. coli by targeting multiple metabolic pathways in an iron-siderophores dependent manner. Moreover, a quantitative proteomics approach was implemented to further elucidate the mechanism of functional metabolites and functional proteins in modulating bacterial virulence. And our findings demonstrated that functional proteins regulated the virulence of E. coli by mediating iron binding, iron-siderophore transmembrane transport, and the biosynthesis and expression of functional metabolites. Interestingly, we found that functional metabolites enhance the virulence of E. coli by specifically modulating the key metabolic pathways involved in purine metabolism, proline metabolism, arginine metabolism and pyrimidine metabolism. Taken together, our study identified for the first time 18 functional metabolites regulating the of E. coli virulence, greatly enriching our understanding of the mechanism of functional metabolites that regulate the E. coli virulence by targeting primary metabolism, which will largely contribute to the development of new strategies to target virulence-based diagnosis and therapy of infections caused by different pathogens.
Project description:To reveal the functional consequences of H-NS modifications, we performed proteome and secretome of Salmonella wild-type and H-NS mutant strains to analyze how phosphorylation impacts the landscape of H-NS-regulated bacterial proteins.
Project description:The aim of the study is investigation of functional consequences of synonymous substitutions in the GATA2 gene in pediatric patients with myelodysplastic syndrome. Whole exome sequencing was performed in order to determine if other genetic conditions contributed to patients' phenotype.
Project description:Understanding the bacterial community structure, and their functional analysis for active bioremediation process is essential to design better and cost effective strategies. Microarray analysis enables us to simultaneously study the functional and phylogenetic markers of hundreds of microorganisms which are involved in active bioremediation process in an environment. We have previously described development of a hybrid 60-mer multibacterial microarray platform (BiodegPhyloChip) for profiling the bacterial communities and functional genes simultaneously in environments undergoing active bioremediation process (Pathak et al; Appl Microbiol Biotechnol,Vol. 90, 1739-1754). The present study involved profiling the status of bacterial communities and functional (biodegradation) genes using the developed 60-mer oligonucleotide microarray BiodegPhyloChip at five contaminated hotspots in the state of Gujarat, in western India. The expression pattern of functional genes (coding for key enzymes in active bioremediation process) at these sites was studied to understand the dynamics of biodegradation in the presence of diverse group of chemicals. The results indicated that the nature of pollutants and their abundance greatly influence the structure of bacterial communities and the extent of expression of genes involved in various biodegradation pathways. In addition, site specific factors also play a pivotal role to affect the microbial community structure as was evident from results of 16S rRNA gene profiling of the five contaminated sites, where the community structure varied from one site to another drastically.