Abstract:Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug … Show more
“…Rather, this information was incorporated into the scoring function that allowed ranking of the potential Kp13 targets within the proteome of this organism, which were then contextualized into metabolic subparts. The complete list of choke-points and centrality measures is also available within Target-Pathogen 51 , as well as the complete metabolic annotation of Kp13. Figure 3 Metabolic network of K. pneumoniae Kp13 represented as a reaction graph.…”
Section: Resultsmentioning
confidence: 99%
“…All previously calculated data were integrated into Target-Pathogen (TP) 51 . TP is a platform developed by our group, which includes a database and web server for drug targets prioritization.…”
Section: Methodsmentioning
confidence: 99%
“…All the data generated and integrated in this study, including protein structures, metabolic annotations, essentiality information and related meta-data is openly available at the Target Pathogen 51 web server interface. The access URL is http://target.sbg.qb.fcen.uba.ar/patho/genome/Kp13 .…”
Klebsiella pneumoniae (Kp) is a globally disseminated opportunistic pathogen that can cause life-threatening infections. It has been found as the culprit of many infection outbreaks in hospital environments, being particularly aggressive towards newborns and adults under intensive care. Many Kp strains produce extended-spectrum β-lactamases, enzymes that promote resistance against antibiotics used to fight these infections. The presence of other resistance determinants leading to multidrug-resistance also limit therapeutic options, and the use of ‘last-resort’ drugs, such as polymyxins, is not uncommon. The global emergence and spread of resistant strains underline the need for novel antimicrobials against Kp and related bacterial pathogens. To tackle this great challenge, we generated multiple layers of ‘omics’ data related to Kp and prioritized proteins that could serve as attractive targets for antimicrobial development. Genomics, transcriptomics, structuromic and metabolic information were integrated in order to prioritize candidate targets, and this data compendium is freely available as a web server. Twenty-nine proteins with desirable characteristics from a drug development perspective were shortlisted, which participate in important processes such as lipid synthesis, cofactor production, and core metabolism. Collectively, our results point towards novel targets for the control of Kp and related bacterial pathogens.
“…Rather, this information was incorporated into the scoring function that allowed ranking of the potential Kp13 targets within the proteome of this organism, which were then contextualized into metabolic subparts. The complete list of choke-points and centrality measures is also available within Target-Pathogen 51 , as well as the complete metabolic annotation of Kp13. Figure 3 Metabolic network of K. pneumoniae Kp13 represented as a reaction graph.…”
Section: Resultsmentioning
confidence: 99%
“…All previously calculated data were integrated into Target-Pathogen (TP) 51 . TP is a platform developed by our group, which includes a database and web server for drug targets prioritization.…”
Section: Methodsmentioning
confidence: 99%
“…All the data generated and integrated in this study, including protein structures, metabolic annotations, essentiality information and related meta-data is openly available at the Target Pathogen 51 web server interface. The access URL is http://target.sbg.qb.fcen.uba.ar/patho/genome/Kp13 .…”
Klebsiella pneumoniae (Kp) is a globally disseminated opportunistic pathogen that can cause life-threatening infections. It has been found as the culprit of many infection outbreaks in hospital environments, being particularly aggressive towards newborns and adults under intensive care. Many Kp strains produce extended-spectrum β-lactamases, enzymes that promote resistance against antibiotics used to fight these infections. The presence of other resistance determinants leading to multidrug-resistance also limit therapeutic options, and the use of ‘last-resort’ drugs, such as polymyxins, is not uncommon. The global emergence and spread of resistant strains underline the need for novel antimicrobials against Kp and related bacterial pathogens. To tackle this great challenge, we generated multiple layers of ‘omics’ data related to Kp and prioritized proteins that could serve as attractive targets for antimicrobial development. Genomics, transcriptomics, structuromic and metabolic information were integrated in order to prioritize candidate targets, and this data compendium is freely available as a web server. Twenty-nine proteins with desirable characteristics from a drug development perspective were shortlisted, which participate in important processes such as lipid synthesis, cofactor production, and core metabolism. Collectively, our results point towards novel targets for the control of Kp and related bacterial pathogens.
“…2A was carried out by an Illumina TruSeq Nano platform at Macrogen Laboratories. De novo assembly was done using the standard procedures from our own prokaryotic assembly pipeline (Sosa et al, 2018), based on SPAdes version 3.9.0 (Bankevich et al, 2012) and SSPACE version 3.0 (Boetzer et al, 2011). Genome annotation was done using the Rapid Annotations Subsystems Technology (RAST) server (Aziz et al, 2008).…”
Section: De Novo Genome Assembly and Annotationmentioning
A Gram-negative pink-pigmented bacillus (named 2A) was isolated from Solanum tuberosum L. cv. Desirée plants that were strikingly more developed, presented increased root hair density, and higher biomass than other potato lines of the same age. The 16S ribosomal DNA sequence, used for comparative gene sequence analysis, indicated that strain 2A belongs to the genus Methylobacterium. Nucleotide identity between Methylobacterium sp. 2A sequenced genome and the rest of the species that belong to the genus suggested that this species has not been described so far. In vitro, potato plants inoculated with Methylobacterium sp. 2A had a better performance when grown under 50 mM NaCl or when infected with Phytophthora infestans. We inoculated Methylobacterium sp. 2A in Arabidopsis thaliana roots and exposed these plants to salt stress (75 mM NaCl). Methylobacterium sp. 2A-inoculated plants, grown in control or salt stress conditions, displayed a higher density of lateral roots (p < 0.05) compared to noninoculated plants. Moreover, under salt stress, they presented a higher number of leaves and larger rosette diameter. In dual confrontation assays, Methylobacterium sp. 2A displayed biocontrol activity against P. infestans, Botrytis cinerea, and Fusarium graminearum, but not against Rhizoctonia solani, and Pythium dissotocum. In addition, we observed that Methylobacterium sp. 2A diminished the size of necrotic lesions and reduced chlorosis when greenhouse potato plants were infected with P. infestans. Methylobacterium sp. 2A produces indole acetic acid, solubilizes mineral phosphate and is able to grow in a N 2 free medium. Whole-genome sequencing revealed metabolic pathways associated with its plant growth promoter capacity. Our results suggest that Methylobacterium sp. 2A is a plant growth-promoting rhizobacteria (PGPR) that can
“…The G+C content is 36.5 mol%. Genome annotation was done using the standard operating procedures from our own prokaryotic annotation pipeline based on Glimmer for open reading frame prediction ( 9 ). Functional annotation included protein function, Gene Ontology (GO) and Clusters of Orthologous Groups (COG) terms, Enzyme Commission (EC) numbers, and Pfam database domains.…”
Lactobacillus helveticus is a lactic acid bacterium used traditionally in the dairy industry, especially in the manufacture of cheeses. We present here the 2,141,841-bp draft genome sequence of L. helveticus strain ATCC 12046, a potential starter strain for improving cheese production.
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