scholarly journals Mabellini: a genome-wide database for understanding the structural proteome and evaluating prospective antimicrobial targets of the emerging pathogen Mycobacterium abscessus

Database ◽  
2019 ◽  
Vol 2019 ◽  
Author(s):  
Marcin J Skwark ◽  
Pedro H M Torres ◽  
Liviu Copoiu ◽  
Bridget Bannerman ◽  
R Andres Floto ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Opportunistic Infections ◽  
Unmet Need ◽  
3D Models ◽  
Mycobacterium Abscessus ◽  
Amino Acid Sequences ◽  
Lung Damage ◽  
Quality Data ◽  
A Genome ◽  
Wide Range

Abstract Mycobacterium abscessus, a rapid growing, multidrug resistant, nontuberculous mycobacteria, can cause a wide range of opportunistic infections, particularly in immunocompromised individuals. M. abscessus has emerged as a growing threat to patients with cystic fibrosis, where it causes accelerated inflammatory lung damage, is difficult and sometimes impossible to treat and can prevent safe transplantation. There is therefore an urgent unmet need to develop new therapeutic strategies. The elucidation of the M. abscessus genome in 2009 opened a wide range of research possibilities in the field of drug discovery that can be more effectively exploited upon the characterization of the structural proteome. Where there are no experimental structures, we have used the available amino acid sequences to create 3D models of the majority of the remaining proteins that constitute the M. abscessus proteome (3394 proteins and over 13 000 models) using a range of up-to-date computational tools, many developed by our own group. The models are freely available for download in an on-line database, together with quality data and functional annotation. Furthermore, we have developed an intuitive and user-friendly web interface (http://www.mabellinidb.science) that enables easy browsing, querying and retrieval of the proteins of interest. We believe that this resource will be of use in evaluating the prospective targets for design of antimicrobial agents and will serve as a cornerstone to support the development of new molecules to treat M. abscessus infections.

scholarly journals ChoK-ing the Pathogenic Bacteria: Potential of Human Choline Kinase Inhibitors as Antimicrobial Agents

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Moad Khalifa ◽  
Ling Ling Few ◽  
Wei Cun See Too
Keyword(s):  
Cell Wall ◽  
Targeted Delivery ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Kinase Inhibitors ◽  
Amino Acid Sequences ◽  
Choline Kinase ◽  
Anticancer Properties ◽  
Wide Range ◽  
Catalytic Sites

Novel antimicrobial agents are crucial to combat antibiotic resistance in pathogenic bacteria. Choline kinase (ChoK) in bacteria catalyzes the synthesis of phosphorylcholine, which is subsequently incorporated into the cell wall or outer membrane. In certain species of bacteria, phosphorylcholine is also used to synthesize membrane phosphatidylcholine. Numerous human ChoK inhibitors (ChoKIs) have been synthesized and tested for anticancer properties. Inhibition of S. pneumoniae ChoK by human ChoKIs showed a promising effect by distorting the cell wall and retarded the growth of this pathogen. Comparison of amino acid sequences at the catalytic sites of putative choline kinases from pathogenic bacteria and human enzymes revealed striking sequence conservation that supports the potential application of currently available ChoKIs for inhibiting bacterial enzymes. We also propose the combined use of ChoKIs and nanoparticles for targeted delivery to the pathogen while shielding the human host from any possible side effects of the inhibitors. More research should focus on the verification of putative bacterial ChoK activities and the characterization of ChoKIs with active enzymes. In conclusion, the presence of ChoK in a wide range of pathogenic bacteria and the distinct function of this enzyme has made it an attractive drug target. This review highlighted the possibility of “choking” bacterial ChoKs by using human ChoKIs.

scholarly journals Functional Analysis and Antivirulence Properties of a New Depolymerase from a Myovirus That Infects Acinetobacter baumannii Capsule K45

2018 ◽  
Vol 93 (4) ◽  
Author(s):  
Hugo Oliveira ◽  
Ana Rita Costa ◽  
Alice Ferreira ◽  
Nico Konstantinides ◽  
Sílvio B. Santos ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Therapeutic Potential ◽  
Host Immune System ◽  
Promising Alternative ◽  
Content Type ◽  
A Genome ◽  
Wide Range

ABSTRACT Acinetobacter baumannii is an important pathogen causative of health care-associated infections and is able to rapidly develop resistance to all known antibiotics, including colistin. As an alternative therapeutic agent, we have isolated a novel myovirus (vB_AbaM_B9) which specifically infects and makes lysis from without in strains of the K45 and K30 capsule types, respectively. Phage B9 has a genome of 93,641 bp and encodes 167 predicted proteins, of which 29 were identified by mass spectrometry. This phage holds a capsule depolymerase (B9gp69) able to digest extracted exopolysaccharides of both K30 and K45 strains and remains active in a wide range of pH values (5 to 9), ionic strengths (0 to 500 mM), and temperatures (20 to 80°C). B9gp69 was demonstrated to be nontoxic in a cell line model of the human lung and to make the K45 strain fully susceptible to serum killing in vitro. Contrary to the case with phage, no resistance development was observed by bacteria targeted with the B9gp69. Therefore, capsular depolymerases may represent attractive antimicrobial agents against A. baumannii infections. IMPORTANCE Currently, phage therapy has revived interest for controlling hard-to-treat bacterial infections. Acinetobacter baumannii is an emerging Gram-negative pathogen able to cause a variety of nosocomial infections. Additionally, this species is becoming more resistant to several classes of antibiotics. Here we describe the isolation of a novel lytic myophage B9 and its recombinant depolymerase. While the phage can be a promising alternative antibacterial agent, its success in the market will ultimately depend on new regulatory frameworks and general public acceptance. We therefore characterized the phage-encoded depolymerase, which is a natural enzyme that can be more easily managed and used. To our knowledge, the therapeutic potential of phage depolymerase against A. baumannii is still unknown. We show for the first time that the K45 capsule type is an important virulence factor of A. baumannii and that capsule removal via the recombinant depolymerase activity helps the host immune system to combat the bacterial infection.

Multidrug-resistant Pseudomonas aeruginosa isolated from ear and wound swabs in some selected hospital laboratories in Sokoto Metropolis, Nigeria

2020 ◽  
Vol 3 ◽  
pp. 31-35
Author(s):  
A. I. Umar ◽  
I. Garba ◽  
M. L. Jidda ◽  
A. M. Ganau ◽  
A. S. Fana ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Opportunistic Infections ◽  
Antibiotic Sensitivity ◽  
Diffusion Method ◽  
Resistance Pattern ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Sensitivity Testing ◽  
Wide Range

Objective: Pseudomonas aeruginosa is a metabolically versatile bacterium that can cause a wide range of severe opportunistic infections in patients with serious underlying conditions and can be found in most communities in Nigeria. The study was to determine the prevalence, resistance pattern and distribution of multiple drug resistant P. aeruginosa (MDR-PA) isolated from ear and wound specimens in patients attending Specialist Hospital Sokoto and Maryam Abacha Women and Children Hospital Sokoto. Materials and Methods: A total of 150 samples were analysed by standard bacteriological methods. Screening for MDR-PA was carried out by antibiotic sensitivity testing using disc diffusion method with ceftazidime (30 µg), ofloxacin (5 µg), cefuroxime (30 µg), cloxacillin (30 µg), amoxicillin (30 µg), ceftriaxone (30 µg), imipenem (10 µg), gentamycin (10 µg) and colistin (10 µg) discs on Mueller Hinton agar. Results: Of a total of 55 (36.7%) isolates of P. aeruginosa strains were obtained, 30 (54.5%) isolates were resistant to imipenem, 31 (56.3%) were resistant to ofloxacin, 44 (80.0%) to gentamycin, 53 (96.3%) to ceftazidime and cefuroxime, 50 (90.9%) to ceftrizone, 54 (98.1%) to cloxacillin and amoxycillin and lastly 15 (27.2%) to colistin. All the isolates were multi drug resistant, this probably due to improper use or over the counter purchase of antibiotics without professional oversight. Conclusion: Almost all the isolates were resistant to all the antibiotics used including colistin. There is need to improve on the public health awareness on the indiscriminate use of antimicrobial agents as it is one of the major ways microbes develop resistance to them.

scholarly journals 3RD BIM/GIS INTEGRATION WORKSHOP AND 15TH 3DGEOINFO CONFERENCE 2020 – PREFACE

2020 ◽  
Vol VI-4/W1-2020 ◽  
pp. 1-1
Author(s):  
K. Wong ◽  
C. Ellul ◽  
J. Morley ◽  
R. Home ◽  
M. Kalantari
Keyword(s):  
Artificial Intelligence ◽  
Data Quality ◽  
3D Models ◽  
Use Cases ◽  
Quality Data ◽  
Ordnance Survey ◽  
3D Data ◽  
Wide Range ◽  
Gis Integration ◽  
Cadastral Systems

Abstract. The interest in and use of 3D models in built environments is rapidly increasing, and they are now a key component of decision-making in areas including climate change mitigation (e.g., calculating solar panel potential, flood modelling, modelling housing age for retrofitting of thermal insulation), urban planning and cadastral systems (modelling rights, restrictions and responsibilities in complex buildings, streamlining the process to issue planning permits, design of existing or new developments) and infrastructure (construction, transport, utility management and modelling, asset management). 3D models are also an integrator for the data underpinning smart cities – knowing where a sensor is in 3D space allows the data to be integrated with the surrounding context – for example, noise data could be integrated with traffic information. Reflecting this interest, national mapping and cadastral agencies (NMCA) including Ordnance Survey (GB) are now increasingly generating 3D mapping at national scale, and there is extensive research as to how this data can be integrated with another emerging source of 3D models such as building information modelling (BIM).These trends were evident during the 3rd BIM/GIS Integration Workshop and 15th 3DGeoInfo 2020 events, which were co-hosted by University College London and Ordnance Survey (GB) in September 2020. The workshop and conference brought together international researchers from academia, industry, government and national mapping and cadastral agencies in the field of 3D geoinformation, in an interdisciplinary gathering of researchers in the fields of data collection, data management, data quality, data analysis, advanced modelling approaches, applications, users, visualisation, augmented reality, artificial intelligence and many more.This year’s theme was Users and Use Cases. The workshop and conference covered a wide range of topics including 3D data acquisition and processing, 3D city modelling and related standards, visualisation and dissemination of 3D data, augmented and virtual reality, 3D and Artificial Intelligence/Machine Learning. Three sessions of the BIM/GIS Integration Workshop were dedicated to Applications of BIM/GIS Integration, and an entire day of 3DGeoInfo 2020 to Users and Use Cases within 3DGeoInfo. Additionally, two sessions were specifically aimed at NMCA participants.Although initially intended to be a face-to-face event in London, the team rapidly adjusted to the emerging COVID-19 situation, identifying an online solution that facilitated and encouraged participant interaction. This meant that the events could still provide a platform for learning, discussion, and exchange of ideas that they have been able to in previous years, as well as providing opportunities to promote international collaboration in these topics. This special issue of the ISPRS International Annals of Photogrammetry, Remote Sensing and Spatial Information Sciences contains 22 papers selected by double-blind peer review carried out by a minimum of three reviewers. It includes research on topics including data modelling, indoor 3D, standards (IndoorML, CityGML, CityJSON), cadastral systems, pedestrian navigation, infrastructure, visualisation, point cloud management, data interoperability, data quality, generating national 3D datasets and planning/permit processes amongst others.

Discovery of Antibacterial Agents Inhibiting the Energy-Coupling Factor (ECF) Transporters by Structure-Based Virtual Screening

2020 ◽  
Author(s):  
Eleonora Diamanti ◽  
Inda Setyawati ◽  
Spyridon Bousis ◽  
leticia mojas ◽  
lotteke Swier ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Energy Coupling ◽  
Coupling Factor ◽  
Design Synthesis ◽  
Screening Design ◽  
Starting Point ◽  
Wide Range ◽  
Vitamin Uptake

Here, we report on the virtual screening, design, synthesis and structure–activity relationships (SARs) of the first class of selective, antibacterial agents against the energy-coupling factor (ECF) transporters. The ECF transporters are a family of transmembrane proteins involved in the uptake of vitamins in a wide range of bacteria. Inhibition of the activity of these proteins could reduce the viability of pathogens that depend on vitamin uptake. Because of their central role in the metabolism of bacteria and their absence in humans, ECF transporters are novel potential antimicrobial targets to tackle infection. The hit compound’s metabolic and plasma stability, the potency (20, MIC Streptococcus pneumoniae = 2 µg/mL), the absence of cytotoxicity and a lack of resistance development under the conditions tested here suggest that this scaffold may represent a promising starting point for the development of novel antimicrobial agents with an unprecedented mechanism of action.<br>

Application of the Innovative and Non-Invasive Technique, Molecular Music Therapy (MMT), Bio-Frequency Therapy, for the Treatment of a Wide Range of Disorders and Pathologies, with Consequent Verification of Molecular Parameters by Using Bi-Digital O-Ring Test (BDORT)

2020 ◽  
Vol 44 (3) ◽  
pp. 177-189
Author(s):  
Momir Dunjic ◽  
Stefano Turini ◽  
Dejan Krstic ◽  
Katarina Dunjic ◽  
Marija Dunjic ◽  
...  
Keyword(s):  
Amino Acid ◽  
Music Therapy ◽  
Amino Acid Sequences ◽  
Sirtuin 1 ◽  
Ring Test ◽  
Invasive Technique ◽  
Specific Gene ◽  
Radiofrequency Therapy ◽  
Wide Range ◽  
Clinical Pictures

Radiofrequency therapy is an unconventional method, already applied for some time, with numerous results in numerous clinical pictures. Our group has developed a software, later called SONGENPROT-SOLARIS, capable of directly converting nucleotide sequences (DNA and/or RNA) and amino acid sequences (polypeptides and proteins) into musical sequences, based on mathematic matrices, designed by the French physicist and musician Joel Sternheimer, which allows to associate a musical note with a nucleotide or an amino acid. Innovation in our software is that, in the algorithm that defines it, a variant is directly implemented that allows the reproduction of sounds, phase-shifted by 30 Hz, between one ear and another reproducing the phenomenon of Binaural Tones, capable of induce a specific brain activity and also the release of particles called solitons. Thanks to this software we have developed a technique called MMT (Molecular Music Therapy) and currently, we are in the phase of applying the technique on a cohort of 91 patients, with a high spectrum of clinical pictures, examining the same, using the technique Bi-Digital-ORing-Test (BDORT), before and after treatment with MMT. Aim of project is to stimulate the expression of a specific gene (the same genetic sequence that the patient listens to, translated into music), only through the use of sound sequences. We have concentrated our attention on three main molecules: Sirtuin-1, Telomers and TP-53. The results obtained with BDORT, after treatment with MMT, showed a significant increase in the values of the three molecules, on all the examined patients, demonstrating the operative efficacy of the technique and the its applicability to numerous diseases. In order to confirm the data obtained by BDORT, we propose, with the help of an accredited laboratory, to perform epigenetic tests on the three parameters listed above, paving the way to understanding how frequencies can influence gene expression.

Heterocycle Compounds with Antimicrobial Activity

2020 ◽  
Vol 26 (8) ◽  
pp. 867-904 ◽  
Author(s):  
Maria Fesatidou ◽  
Anthi Petrou ◽  
Geronikaki Athina
Keyword(s):  
Heterocyclic Compounds ◽  
Bacterial Infections ◽  
Scientific Community ◽  
Antimicrobial Agents ◽  
Fungal Infections ◽  
Biological Activities ◽  
Literature Survey ◽  
New Findings ◽  
Wide Range ◽  
Number Of Microorganisms

Background: Bacterial infections are a growing problem worldwide causing morbidity and mortality mainly in developing countries. Moreover, the increased number of microorganisms, developing multiple resistances to known drugs, due to abuse of antibiotics, is another serious problem. This problem becomes more serious for immunocompromised patients and those who are often disposed to opportunistic fungal infections. Objective: The objective of this manuscript is to give an overview of new findings in the field of antimicrobial agents among five-membered heterocyclic compounds. These heterocyclic compounds especially five-membered attracted the interest of the scientific community not only for their occurrence in nature but also due to their wide range of biological activities. Method: To reach our goal, a literature survey that covers the last decade was performed. Results: As a result, recent data on the biological activity of thiazole, thiazolidinone, benzothiazole and thiadiazole derivatives are mentioned. Conclusion: It should be mentioned that despite the progress in the development of new antimicrobial agents, there is still room for new findings. Thus, research still continues.

scholarly journals Role of husband’s attitude towards the usage of contraceptives for unmet need of family planning among married women of reproductive age in Pakistan

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Muhammad Farhan Asif ◽  
Zahid Pervaiz ◽  
Jawad Rahim Afridi ◽  
Ghulam Abid ◽  
Zohra S. Lassi
Keyword(s):  
Family Planning ◽  
Unmet Need ◽  
Wealth Quintile ◽  
Married Women ◽  
Reproductive Age ◽  
Women Of Reproductive Age ◽  
Family Planning Programs ◽  
Contraception Use ◽  
Wide Range

Abstract Background Family planning services deliver a wide range of benefits to the well-being of females and the community. It can curtail the risk of maternal and neonatal mortality through the reduction in abortions and pregnancies. The government of Pakistan has been struggling to convince people about the usefulness of family planning programs. However, different factors related to social norms, values, and culture are important to determine the success of these programs. One such factor is the patriarchal structure of Pakistani society where most of the household decisions are made by men. The objective of this research is to examine the role of the husband’s attitude towards the usage of contraceptives for the unmet need of family planning (UMNFP) among married women of reproductive age (MWRA) in Pakistan. Method The dataset of Pakistan Demographic and Health Survey 2017–18 is utilized to examine the role of the husband’s attitude towards the usage of contraceptives in UMNFP among MWRA in Pakistan. Results The UMNFP was considerably lower among MWRA between 40 years and above compared to women 15–19 years. The odds of UMNFP were higher among women and men who were educated up to the primary level compared to those with no education. Odds of UMNFP were higher among women from the poor wealth quintile compared to the poorest wealth quintile; similarly, it was significantly lower among women who were from the richer and the richest wealth quintile compared to the poorest wealth quintile. The odds of UMNFP were lower among women who were employed compared to those who were not employed. Lastly, the odds of UMNFP were higher among women whose husbands opposed to using contraceptives, who perceived that there was a religious prohibition for such use and when a decision on the contraception use was solely made by the husband. Conclusions Husband’s attitude towards the usage of contraceptives is an important predictor of UMNFP. Liaising with the community and religious leaders to persuade people particularly men about the usefulness of family planning programs and encouraging men to understand their women’s say in using contraceptives should be encouraged.

scholarly journals Genetic, lifestyle, and health-related characteristics of adults without celiac disease who follow a gluten-free diet: a population-based study of 124,447 participants

2020 ◽  
Author(s):  
Thomas J Littlejohns ◽  
Amanda Y Chong ◽  
Naomi E Allen ◽  
Matthew Arnold ◽  
Kathryn E Bradbury ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Genome Wide Association Study ◽  
Population Based ◽  
Gluten Free Diet ◽  
Hospital Inpatient ◽  
Gluten Free ◽  
A Genome ◽  
Wide Range ◽  
Health Related ◽  
Reported Health

ABSTRACT Background The number of gluten-free diet followers without celiac disease (CD) is increasing. However, little is known about the characteristics of these individuals. Objectives We address this issue by investigating a wide range of genetic and phenotypic characteristics in association with following a gluten-free diet. Methods The cross-sectional association between lifestyle and health-related characteristics and following a gluten-free diet was investigated in 124,447 women and men aged 40–69 y from the population-based UK Biobank study. A genome-wide association study (GWAS) of following a gluten-free diet was performed. Results A total of 1776 (1.4%) participants reported following a gluten-free diet. Gluten-free diet followers were more likely to be women, nonwhite, highly educated, living in more socioeconomically deprived areas, former smokers, have lost weight in the past year, have poorer self-reported health, and have made dietary changes as a result of illness. Conversely, these individuals were less likely to consume alcohol daily, be overweight or obese, have hypertension, or use cholesterol-lowering medication. Participants with hospital inpatient diagnosed blood and immune mechanism disorders (OR: 1.62; 95% CI: 1.18, 2.21) and non-CD digestive system diseases (OR: 1.58; 95% CI: 1.42, 1.77) were more likely to follow a gluten-free diet. The GWAS demonstrated that no genetic variants were associated with being a gluten-free diet follower. Conclusions Gluten-free diet followers have a better cardiovascular risk profile than non-gluten-free diet followers but poorer self-reported health and a higher prevalence of blood and immune disorders and digestive conditions. Reasons for following a gluten-free diet warrant further investigation.

scholarly journals Revealing biophysical properties of KfrA-type proteins as a novel class of cytoskeletal, coiled-coil plasmid-encoded proteins

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
M. Adamczyk ◽  
E. Lewicka ◽  
R. Szatkowska ◽  
H. Nieznanska ◽  
J. Ludwiczak ◽  
...  
Keyword(s):  
Dna Binding ◽  
Host Range ◽  
Coiled Coil ◽  
Amino Acid Sequences ◽  
Broad Host Range ◽  
Biophysical Properties ◽  
Dna Binding Sites ◽  
In Silico Studies ◽  
Wide Range

Abstract Background DNA binding KfrA-type proteins of broad-host-range bacterial plasmids belonging to IncP-1 and IncU incompatibility groups are characterized by globular N-terminal head domains and long alpha-helical coiled-coil tails. They have been shown to act as transcriptional auto-regulators. Results This study was focused on two members of the growing family of KfrA-type proteins encoded by the broad-host-range plasmids, R751 of IncP-1β and RA3 of IncU groups. Comparative in vitro and in silico studies on KfrAR751 and KfrARA3 confirmed their similar biophysical properties despite low conservation of the amino acid sequences. They form a wide range of oligomeric forms in vitro and, in the presence of their cognate DNA binding sites, they polymerize into the higher order filaments visualized as “threads” by negative staining electron microscopy. The studies revealed also temperature-dependent changes in the coiled-coil segment of KfrA proteins that is involved in the stabilization of dimers required for DNA interactions. Conclusion KfrAR751 and KfrARA3 are structural homologues. We postulate that KfrA type proteins have moonlighting activity. They not only act as transcriptional auto-regulators but form cytoskeletal structures, which might facilitate plasmid DNA delivery and positioning in the cells before cell division, involving thermal energy.

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