scholarly journals Systems Biology–Derived Genetic Signatures of Mastitis in Dairy Cattle: A New Avenue for Drug Repurposing

Animals ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 29
Author(s):  
Somayeh Sharifi ◽  
Maryam Lotfi Shahreza ◽  
Abbas Pakdel ◽  
James M. Reecy ◽  
Nasser Ghadiri ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
Clinical Signs ◽  
Drug Repurposing ◽  
Severe Infection ◽  
Label Propagation ◽  
Global Network ◽  
Biological Information ◽  
Online Data ◽  
Data Repositories ◽  
E Coli

Mastitis, a disease with high incidence worldwide, is the most prevalent and costly disease in the dairy industry. Gram-negative bacteria such as Escherichia coli (E. coli) are assumed to be among the leading agents causing acute severe infection with clinical signs. E. Coli, environmental mastitis pathogens, are the primary etiological agents of bovine mastitis in well-managed dairy farms. Response to E. Coli infection has a complex pattern affected by genetic and environmental parameters. On the other hand, the efficacy of antibiotics and/or anti-inflammatory treatment in E. coli mastitis is still a topic of scientific debate, and studies on the treatment of clinical cases show conflicting results. Unraveling the bio-signature of mastitis in dairy cattle can open new avenues for drug repurposing. In the current research, a novel, semi-supervised heterogeneous label propagation algorithm named Heter-LP, which applies both local and global network features for data integration, was used to potentially identify novel therapeutic avenues for the treatment of E. coli mastitis. Online data repositories relevant to known diseases, drugs, and gene targets, along with other specialized biological information for E. coli mastitis, including critical genes with robust bio-signatures, drugs, and related disorders, were used as input data for analysis with the Heter-LP algorithm. Our research identified novel drugs such as Glibenclamide, Ipratropium, Salbutamol, and Carbidopa as possible therapeutics that could be used against E. coli mastitis. Predicted relationships can be used by pharmaceutical scientists or veterinarians to find commercially efficacious medicines or a combination of two or more active compounds to treat this infectious disease.

scholarly journals The use of the Heter-LP algorithm to reposition antibiotics for managing E. coli mastitis in dairy cattle

2020 ◽  
Author(s):  
Somayeh Sharifi ◽  
Maryam Lotfi Shahreza ◽  
Abbas Pakdel ◽  
James M. Reecy ◽  
Nasser Ghadiri ◽  
...  
Keyword(s):  
Drug Repositioning ◽  
Bovine Mastitis ◽  
Biological Information ◽  
Data Repositories ◽  
E Coli ◽  
Novel Drugs ◽  
High Incidence ◽  
On Line ◽  
Etiological Agents ◽  
Mastitis Pathogens

Abstract Mastitis, a disease with high incidence worldwide, is the most prevalent and costly disease in the dairy industry. Environmental mastitis pathogens, such as Escherichia coli (E. coli), are major etiological agents of bovine mastitis in well-managed dairy farms. However, there is still a need to develop more efficient, safe, and economical treatments for mastitis. In the current research, Heter-LP, a new system biology-based method of drug repositioning, was applied to potentially identify novel therapeutic avenues for the treatment of E. coli mastitis. On-line data repositories relevant to known diseases, drugs, and gene targets along with other specialized biological information for E. coli mastitis, including key genes with robust bio-signatures, drugs and related diseases were used as input data for analysis with the Heter-LP algorithm. Our analyses identified novel drugs such as Glibenclamide, Ipratropium, Salbutamol, and Carbidopa as possible therapeutics that could be used against E. coli mastitis. Predicted relationships can be used by pharmaceutical scientists or veterinarians to find commercially efficacious medicines or combination of two or more active compounds to treat mastitis.

scholarly journals Molecular identification and antimicrobial resistence of Escherichia fergusonii and Escherichia coli from dairy cattle with diarrhoea

2018 ◽  
Vol 63 (No. 3) ◽  
pp. 110-116 ◽  
Author(s):  
U. Parin ◽  
S. Kirkan ◽  
SS Arslan ◽  
HT Yuksel
Keyword(s):  
Antibiotic Resistance ◽  
Dairy Cattle ◽  
Culture Media ◽  
Clinical Signs ◽  
Hypothetical Protein ◽  
Cellulose Synthase ◽  
Penicillin G ◽  
Sequencing Analysis ◽  
E Coli ◽  
Holstein Friesian

The aim of this study was to determine the incidence of Escherichia fergusonii in dairy cattle with clinical signs of diarrhoea. The specimens were obtained from three different farms in Denizli province of Turkey, between August 2016 and December 2016. Rectal contents of 57 Holstein-friesian dairy cattle with diarrhoea were collected from farms located in the Aegean Region (Denizli province, Turkey). Rectal swabs were inoculated into enrichment, differential and selective culture media. A total of 49 (86%) Escherichia spp. were isolated by phenotypic identification from 57 rectal swab samples. Presumptive E. fergusonii isolates were tested with the API 20E identification kit and all isolates (100%) were identified as E. coli. Primers targeting specific E. coli and E. fergusonii and genes, including the beta-glucuronidase enzyme, conserved hypothetical cellulose synthase protein and regulator of cellulose synthase and hypothetical protein, putative transcriptional activator for multiple antibiotic resistance were used for detection and differentiation of E. coli and E. fergusonii. Thirteen of the 49 E. coli-verified isolates were identified as E. fergusonii after duplex PCR using EFER 13- and EFER YP-specific primers. Confirmation of strain identity was conducted using Sanger sequencing analysis. The rates of antibiotic resistance of E. fergusonii to penicillin G and erythromycin were 100% and 77%, respectively. In conclusion, field strains of E. fergusonii were detected in cattle with diarrhoea in Turkey, and the strains were found to be resistant to multiple antibiotics.

scholarly journals Wolman’s disease presenting with secondary hemophagocytic lymphohistiocytosis: a case report from Saudi Arabia and literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fahad Alabbas ◽  
Ghaleb Elyamany ◽  
Talal Alanzi ◽  
Tahani Bin Ali ◽  
Fatma Albatniji ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Metabolic Disorder ◽  
Clinical Signs ◽  
Failure To Thrive ◽  
Severe Infection ◽  
Signs And Symptoms ◽  
Immune Deficiency Syndrome ◽  
Autoimmune Disorder ◽  
Deficiency Syndrome ◽  
Homozygous Deletion

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal syndrome that is characterized by strong activation of the immune system from hyperinflammatory cytokines. Symptoms of HLH patients include fever, hepatosplenomegaly, cytopenia, and hyperferritinemia. Inherited HLH is classified as primary, whereas secondary HLH (sHLH) occurs when acquired from non-inherited reasons that include severe infection, immune deficiency syndrome, autoimmune disorder, neoplasm, and metabolic disorder. Wolman’s disease (WD) is a rare and fatal infantile metabolic disorder caused by lysosomal acid lipase deficiency, that exhibits similar clinical signs and symptoms as HLH. This paper reports the case of an infant diagnosed with WD and who presented with sHLH. Case presentation A 4-month-old infant presenting with hepatosplenomegaly, failure to thrive, and other abnormalities. WD diagnosis was confirmed by the presence of the LIPA gene homozygous deletion c.(428 + 1_967-1)_(*1_?)del. The infant also met the HLH-2004 diagnostic criteria. Conclusions Metabolic disorder such as WD should be investigated in infants fulfilling the HLH criteria to diagnose the underlying condition. More studies are needed to understand the link between WD and sHLH and to identify appropriate therapies.

scholarly journals metaXplor: an interactive viral and microbial metagenomic data manager

GigaScience ◽  
2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Guilhem Sempéré ◽  
Adrien Pétel ◽  
Magsen Abbé ◽  
Pierre Lefeuvre ◽  
Philippe Roumagnac ◽  
...  
Keyword(s):  
Heterogeneous Data ◽  
Metagenomic Data ◽  
Online Data ◽  
Data Repositories ◽  
Ongoing Research ◽  
Efficient Management ◽  
Public Data ◽  
Reference Databases ◽  
Interactive Data ◽  
User Friendly

Abstract Background Efficiently managing large, heterogeneous data in a structured yet flexible way is a challenge to research laboratories working with genomic data. Specifically regarding both shotgun- and metabarcoding-based metagenomics, while online reference databases and user-friendly tools exist for running various types of analyses (e.g., Qiime, Mothur, Megan, IMG/VR, Anvi'o, Qiita, MetaVir), scientists lack comprehensive software for easily building scalable, searchable, online data repositories on which they can rely during their ongoing research. Results metaXplor is a scalable, distributable, fully web-interfaced application for managing, sharing, and exploring metagenomic data. Being based on a flexible NoSQL data model, it has few constraints regarding dataset contents and thus proves useful for handling outputs from both shotgun and metabarcoding techniques. By supporting incremental data feeding and providing means to combine filters on all imported fields, it allows for exhaustive content browsing, as well as rapid narrowing to find specific records. The application also features various interactive data visualization tools, ways to query contents by BLASTing external sequences, and an integrated pipeline to enrich assignments with phylogenetic placements. The project home page provides the URL of a live instance allowing users to test the system on public data. Conclusion metaXplor allows efficient management and exploration of metagenomic data. Its availability as a set of Docker containers, making it easy to deploy on academic servers, on the cloud, or even on personal computers, will facilitate its adoption.

scholarly journals Repurposing of the Tamoxifen Metabolites to Combat Infections by Multidrug-Resistant Gram-Negative Bacilli

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 336
Author(s):  
Andrea Miró-Canturri ◽  
Rafael Ayerbe-Algaba ◽  
Andrea Vila-Domínguez ◽  
Manuel E. Jiménez-Mejías ◽  
Jerónimo Pachón ◽  
...  
Keyword(s):  
Outer Membrane Proteins ◽  
Bacterial Load ◽  
Drug Repurposing ◽  
Multidrug Resistant ◽  
E Coli ◽  
Immune System Cell ◽  
Tamoxifen Metabolites ◽  
Potential Alternative ◽  
Immunocompetent Mice ◽  
Time Kill

The development of new strategic antimicrobial therapeutic approaches, such as drug repurposing, has become an urgent need. Previously, we reported that tamoxifen presents therapeutic efficacy against multidrug-resistant (MDR) Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli in experimental infection models by modulating innate immune system cell traffic. The main objective of this study was to analyze the activity of N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen, three major metabolites of tamoxifen, against these pathogens. We showed that immunosuppressed mice infected with A. baumannii, P. aeruginosa, or E. coli in peritoneal sepsis models and treated with tamoxifen at 80 mg/kg/d for three days still reduced the bacterial load in tissues and blood. Moreover, it increased mice survival to 66.7% (for A. baumannii and E. coli) and 16.7% (for P. aeruginosa) when compared with immunocompetent mice. Further, susceptibility and time-kill assays showed that N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen exhibited minimum inhibitory concentration of the 90% of the isolates (MIC90) values of 16 mg/L, and were bactericidal against clinical isolates of A. baumannii and E. coli. This antimicrobial activity of tamoxifen metabolites paralleled an increased membrane permeability of A. baumannii and E. coli without affecting their outer membrane proteins profiles. Together, these data showed that tamoxifen metabolites presented antibacterial activity against MDR A. baumannii and E. coli, and may be a potential alternative for the treatment of infections caused by these two pathogens.

scholarly journals Retrograde Axonal Transport: a Major Transmission Route of Enterovirus 71 in Mice

2007 ◽  
Vol 81 (17) ◽  
pp. 8996-9003 ◽  
Author(s):  
Che-Szu Chen ◽  
Yi-Chuan Yao ◽  
Shin-Chao Lin ◽  
Yi-Ping Lee ◽  
Ya-Fang Wang ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Early Stage ◽  
Clinical Signs ◽  
Enterovirus 71 ◽  
Severe Infection ◽  
Dependent Manner ◽  
Transmission Route ◽  
Brain Infection ◽  
Reverse Pattern ◽  
Clinical Illness

ABSTRACT Inoculation of enterovirus 71 (EV71) by the oral (p.o.), intramuscular (i.m.), or intracranial route resulted in brain infection, flaccid paralysis, pulmonary dysfunction, and death of 7-day-old mice. The lag time of disease progression indicated that neuroinvasion from the inoculation sites was a prerequisite for the development of the clinical signs. Although EV71 p.o. inoculation led to a persistent viremia and a transient increase in blood-brain barrier permeability at the early stage of the infection, only low levels of virus, which led to neither severe infection nor clinical illness, could be detected in the brain, suggesting that hematogenous transport might not represent a major transmission route. In the spinal cord, following both p.o. and hind limb i.m. inoculation, the virus first appeared and increased rapidly in the lower segments, especially at the anterior horn areas, and then spread to the upper segments and brain in the presence of viremia. A reverse pattern, with the virus being first detected in the upper segment, was observed when the virus was i.m. inoculated in the forelimb. Colchicine, a fast axonal transport inhibitor, but not sciatic nerve transection reduced EV71 neuroinvasion in a dose-dependent manner, indicating a neuronal transmission of the virus.

scholarly journals Antimicrobial-Resistant Enteric Bacteria from Dairy Cattle

2006 ◽  
Vol 73 (1) ◽  
pp. 156-163 ◽  
Author(s):  
Ashish A. Sawant ◽  
Narasimha V. Hegde ◽  
Beth A. Straley ◽  
Sarah C. Donaldson ◽  
Brenda C. Love ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
Dna Hybridization ◽  
Bacterial Species ◽  
Dairy Herd ◽  
Enteric Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli ◽  
Predominant Species ◽  
Lactating Dairy Cattle

ABSTRACT A study was conducted to understand the descriptive and molecular epidemiology of antimicrobial-resistant gram-negative enteric bacteria in the feces of healthy lactating dairy cattle. Gram-negative enteric bacteria resistant to ampicillin, florfenicol, spectinomycin, and tetracycline were isolated from the feces of 35, 8, 5, and 42% of 213 lactating cattle on 74, 39, 9, 26, and 82% of 23 farms surveyed, respectively. Antimicrobial-resistant gram-negative bacteria accounted for 5 (florfenicol) to 14% (tetracycline) of total gram-negative enteric microflora. Nine bacterial species were isolated, of which Escherichia coli (87%) was the most predominant species. MICs showing reduced susceptibility to ampicillin, ceftiofur, chloramphenicol, florfenicol, spectinomycin, streptomycin, and tetracycline were observed in E. coli isolates. Isolates exhibited resistance to ampicillin (48%), ceftiofur (11%), chloramphenicol (20%), florfenicol (78%), spectinomycin (18%), and tetracycline (93%). Multidrug resistance (≥3 to 6 antimicrobials) was seen in 40% of E. coli isolates from healthy lactating cattle. Of 113 tetracycline-resistant E. coli isolates, tet(B) was the predominant resistance determinant and was detected in 93% of isolates, while the remaining 7% isolates carried the tet(A) determinant. DNA-DNA hybridization assays revealed that tet determinants were located on the chromosome. Pulsed-field gel electrophoresis revealed that tetracycline-resistant E. coli isolates (n = 99 isolates) belonged to 60 subtypes, which is suggestive of a highly diverse population of tetracycline-resistant organisms. On most occasions, E. coli subtypes, although shared between cows within the herd, were confined mostly to a dairy herd. The findings of this study suggest that commensal enteric E. coli from healthy lactating cattle can be an important reservoir for tetracycline and perhaps other antimicrobial resistance determinants.

Isolation of Escherichia coli serotype O157:H7 and other Shiga-like-toxin-producing E. coli from dairy cattle.

1991 ◽  
Vol 29 (5) ◽  
pp. 985-989 ◽  
Author(s):  
J G Wells ◽  
L D Shipman ◽  
K D Greene ◽  
E G Sowers ◽  
J H Green ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dairy Cattle ◽  
E Coli

Escherichia coli O157 in Cull Dairy Cows on Farm and at Slaughter

1997 ◽  
Vol 60 (11) ◽  
pp. 1386-1387 ◽  
Author(s):  
DANIEL H. RICE ◽  
ERIC D. EBEL ◽  
DALE D. HANCOCK ◽  
THOMAS E. BESSER ◽  
DONALD E. HERRIOTT ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dairy Cattle ◽  
Dairy Cows ◽  
Dairy Herds ◽  
Escherichia Coli O157 ◽  
E Coli ◽  
Cull Cows ◽  
On Farm

Cull dairy cattle both on the farm and at slaughter from herds in the states of Idaho, Oregon, and Washington were surveyed for Escherichia coli O157 by culturing fecal swab samples. A total of 205 cull cows from 19 dairy herds were sampled on the farm of origin; 7 (3.4%) tested positive for E. coli O157. A total of 103 cull cows from 15 dairy herds were sampled at slaughter; 4 (3.9%) were positive for E. coli O157. Eighty-nine cull cows were sampled both at the farm and at slaughter; 2 (2.2%) were positive in both locations, 3 (3.3%) only on the farm, and 2 (2.2%) only at the slaughter plant. Seven (7.9%) of the 89 cull cows tracked from farm to slaughter were positive in at least one location. This suggests a higher prevalence of E. coli O157 in cull dairy cattle than previously has been reported to occur in other ages and classes of cattle.

scholarly journals CausalMGM: an interactive web-based causal discovery tool

2020 ◽  
Vol 48 (W1) ◽  
pp. W597-W602 ◽  
Author(s):  
Xiaoyu Ge ◽  
Vineet K Raghu ◽  
Panos K Chrysanthis ◽  
Panayiotis V Benos
Keyword(s):  
Observational Data ◽  
High Throughput Sequencing ◽  
Graphical Model ◽  
The Cancer Genome Atlas ◽  
Causal Discovery ◽  
Automated Identification ◽  
Online Data ◽  
Data Repositories ◽  
Web Based ◽  
Cause And Effect

Abstract High-throughput sequencing and the availability of large online data repositories (e.g. The Cancer Genome Atlas and Trans-Omics for Precision Medicine) have the potential to revolutionize systems biology by enabling researchers to study interactions between data from different modalities (i.e. genetic, genomic, clinical, behavioral, etc.). Currently, data mining and statistical approaches are confined to identifying correlates in these datasets, but researchers are often interested in identifying cause-and-effect relationships. Causal discovery methods were developed to infer such cause-and-effect relationships from observational data. Though these algorithms have had demonstrated successes in several biomedical applications, they are difficult to use for non-experts. So, there is a need for web-based tools to make causal discovery methods accessible. Here, we present CausalMGM (http://causalmgm.org/), the first web-based causal discovery tool that enables researchers to find cause-and-effect relationships from observational data. Web-based CausalMGM consists of three data analysis tools: (i) feature selection and clustering; (ii) automated identification of cause-and-effect relationships via a graphical model; and (iii) interactive visualization of the learned causal (directed) graph. We demonstrate how CausalMGM enables an end-to-end exploratory analysis of biomedical datasets, giving researchers a clearer picture of its capabilities.

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