scholarly journals Enterobacteria virulence factor prediction server

2017 ◽  
Vol 7 (1.1) ◽  
pp. 435
Author(s):  
M Thirunavu karasu ◽  
K Dinakaran ◽  
E N. Sathishkumar ◽  
S Gnanendra
Keyword(s):  
Virulence Factor ◽  
Drug Targets ◽  
Critical Role ◽  
Bacterial Genome ◽  
Drastic Increase ◽  
Prediction Server ◽  
Sensitivity Specificity ◽  
Novel Drug ◽  
Novel Drug Targets ◽  
Selection Of

The continuous usage of antibiotics has resulted in the increase of multidrug resistance in the bacteria. The drastic increase in the bacterial genome projects has paved a path for the identification of potentially novel virulence-associated factors and their possibility as novel drug targets. Thus in the present study, we have implemented SMO classifiers for the better prediction of proteins based on individual protein sequences amino acid composition (AAC) and the performance of evaluation was checked via threshold dependent parameters such as Sensitivity, Specificity, Accuracy, and Mathew correlation coefficient. The predictions are based on the dataset incorporated in the database of five major virulence factors from six pathogens of Enterobacteriacae.This comprehensive database can serve as a source for the selection of significant virulence factor based on the intellectual Gene ontology terms that play a critical role in the pathogenesis and its surveillance in the host.

scholarly journals Opportunities and Challenges of Bacterial Glycosylation for the Development of Novel Antibacterial Strategies

2021 ◽  
Vol 12 ◽  
Author(s):  
Liubov Yakovlieva ◽  
Julius A. Fülleborn ◽  
Marthe T. C. Walvoort
Keyword(s):  
Virulence Factors ◽  
Drug Targets ◽  
Bacterial Population ◽  
Molecular Mimicry ◽  
Bacterial Pathogens ◽  
Current Status ◽  
Novel Drug ◽  
Bacterial Glycosylation ◽  
Novel Drug Targets ◽  
Selection Of

Glycosylation is a ubiquitous process that is universally conserved in nature. The various products of glycosylation, such as polysaccharides, glycoproteins, and glycolipids, perform a myriad of intra- and extracellular functions. The multitude of roles performed by these molecules is reflected in the significant diversity of glycan structures and linkages found in eukaryotes and prokaryotes. Importantly, glycosylation is highly relevant for the virulence of many bacterial pathogens. Various surface-associated glycoconjugates have been identified in bacteria that promote infectious behavior and survival in the host through motility, adhesion, molecular mimicry, and immune system manipulation. Interestingly, bacterial glycosylation systems that produce these virulence factors frequently feature rare monosaccharides and unusual glycosylation mechanisms. Owing to their marked difference from human glycosylation, bacterial glycosylation systems constitute promising antibacterial targets. With the rise of antibiotic resistance and depletion of the antibiotic pipeline, novel drug targets are urgently needed. Bacteria-specific glycosylation systems are especially promising for antivirulence therapies that do not eliminate a bacterial population, but rather alleviate its pathogenesis. In this review, we describe a selection of unique glycosylation systems in bacterial pathogens and their role in bacterial homeostasis and infection, with a focus on virulence factors. In addition, recent advances to inhibit the enzymes involved in these glycosylation systems and target the bacterial glycan structures directly will be highlighted. Together, this review provides an overview of the current status and promise for the future of using bacterial glycosylation to develop novel antibacterial strategies.

Genomics in target and drug discovery

2003 ◽  
Vol 31 (2) ◽  
pp. 429-432 ◽  
Author(s):  
M. van Duin ◽  
H. Woolson ◽  
D. Mallinson ◽  
D. Black
Keyword(s):  
Drug Targets ◽  
Therapeutic Drug ◽  
Human Macrophage ◽  
Therapeutic Area ◽  
Microarray Experiments ◽  
Area Of Interest ◽  
Macrophage Foam Cells ◽  
Novel Drug ◽  
Novel Drug Targets ◽  
Selection Of

Genomics-based discovery of novel therapeutic drug targets requires the design of well-controlled biological or pharmacological experiments with experimental questions and hypotheses that relate to the therapeutic area of interest. This will aid the validation level of differentially expressed genes and hence facilitate the de-selection of the genes that are identified in microarray experiments. We here provide an example of how this approach is followed in the manipulation of human macrophage foam cells towards the discovery of novel drug targets for treatment of atherosclerosis.

Novel drug targets in 2019

2020 ◽  
Vol 19 (5) ◽  
pp. 300-300 ◽  
Author(s):  
Sorin Avram ◽  
Liliana Halip ◽  
Ramona Curpan ◽  
Tudor I. Oprea
Keyword(s):  
Drug Targets ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals Identification of Polo-like kinases as potential novel drug targets for influenza A virus

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Marie O. Pohl ◽  
Jessica von Recum-Knepper ◽  
Ariel Rodriguez-Frandsen ◽  
Caroline Lanz ◽  
Emilio Yángüez ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Drug Targets ◽  
Influenza A ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

10.3791/54738 ◽  
2016 ◽  
Author(s):  
Eamonn Morrison ◽  
Patty Wai ◽  
Andri Leonidou ◽  
Philip Bland ◽  
Saira Khalique ◽  
...  
Keyword(s):  
Functional Genomics ◽  
Cancer Cell ◽  
Drug Targets ◽  
Cell Spheroid ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals Multi-omics data integration reveals novel drug targets in hepatocellular carcinoma

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christos Dimitrakopoulos ◽  
Sravanth Kumar Hindupur ◽  
Marco Colombi ◽  
Dritan Liko ◽  
Charlotte K. Y. Ng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Targets ◽  
Mtor Signaling ◽  
Omics Data ◽  
Genetic Changes ◽  
Genetic Aberrations ◽  
Functional Consequences ◽  
Novel Drug ◽  
Novel Drug Targets ◽  
Omics Data Integration

Abstract Background Genetic aberrations in hepatocellular carcinoma (HCC) are well known, but the functional consequences of such aberrations remain poorly understood. Results Here, we explored the effect of defined genetic changes on the transcriptome, proteome and phosphoproteome in twelve tumors from an mTOR-driven hepatocellular carcinoma mouse model. Using Network-based Integration of multi-omiCS data (NetICS), we detected 74 ‘mediators’ that relay via molecular interactions the effects of genetic and miRNA expression changes. The detected mediators account for the effects of oncogenic mTOR signaling on the transcriptome, proteome and phosphoproteome. We confirmed the dysregulation of the mediators YAP1, GRB2, SIRT1, HDAC4 and LIS1 in human HCC. Conclusions This study suggests that targeting pathways such as YAP1 or GRB2 signaling and pathways regulating global histone acetylation could be beneficial in treating HCC with hyperactive mTOR signaling.

Abstract P283: CCL5 Acts As A Vasoconstrictor On Penetrating Arterioles In The Cerebral Circulation By Enhancing 20-HETE Activity

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Reece F Crumpler ◽  
Huawei Zhang ◽  
Xing Fang ◽  
Shaoxun Wang ◽  
Baoying Zheng ◽  
...  
Keyword(s):  
Drug Targets ◽  
Perfusion Pressure ◽  
Synthesis Inhibitor ◽  
Atherosclerosis Risk In Communities ◽  
Cyp Enzymes ◽  
Sd Rats ◽  
Sodium Regulation ◽  
Novel Drug ◽  
The Brain ◽  
Novel Drug Targets

20-HETE is synthesized from arachidonic acid by cytochrome P450 (CYP) enzymes 4A and 4F. Inactivating mutations in the CYP enzymes that produce 20-HETE are associated with hypertension and stroke in man. We previously revealed that inactivating variants of CYP4A/F enzymes are associated with dementia in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NS) population. 20-HETE is involved with sodium regulation in the kidney and is a powerful vasoconstrictor. It was recently discovered that CCL5 and 20-HETE share the same receptor, GPR75. We previously found that 20-HETE constricts and augments the myogenic response (MR) of the middle cerebral artery (MCA) and renal afferent arteriole. However, whether CCL5 has any effect on penetrating arterioles (PAs) and interacts with 20-HETE is unknown. We found that GPR75 is expressed in PAs and pericytes in the brain. CYP4A is also expressed in pericytes and is inversely proportional to levels of GPR75 in the brain. In the present study, we found that 20-HETE contributes to the basal myogenic tone of PAs in SD rats. Administration of HET0016, a 20-HETE synthesis inhibitor, dilated the PA by 34 ± 3% (n = 6) under 10 mmHg perfusion pressure. Administration of WIT003, a 20-HETE agonist, constricted the vessel by 23 ± 4% (n = 6) under the same perfusion pressure. We found that CCL5 also reduced PA diameter by 20 ± 4% (n = 7) in SD rats under 10 mmHg perfusion pressure. Moreover, we compared the response to CCL5 in SS rats that are 20-HETE deficient and SS.CYP4A1 transgenic rats in which 20-HETE production is restored. PAs isolated from SS rats treated with 0.1 nM CCL5 constricted by 9 ± 5% (n = 6) while those treated with 10 nM constricted by 12 ± 3% (n = 6). CCL5 had a greater response in PAs from the SS.CYP4A1 strain, and the diameter of the PAs constricted by 14 ± 2% (n = 5) and 24 ± 5% (n = 5) in response to 0.1 and 10 nM CCL5, respectively. These results demonstrate that CCL5 has a direct effect on PAs similar to 20-HETE that acts via the GPR75 receptor. However, further study is needed to determine how CCL5 and 20-HETE interact to promote vasoconstriction. These studies would help further understand the involvement of 20-HETE in disease and potentially identify novel drug targets.

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