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 Identification of Bacterial Cell Wall Lyases via Pseudo Amino Acid Composition

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Xin-Xin Chen ◽  
Hua Tang ◽  
Wen-Chao Li ◽  
Hao Wu ◽  
Wei Chen ◽  
...  
Keyword(s):  
Cell Wall ◽  
Bacterial Cell ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Cell Structure ◽  
Bacterial Cell Wall ◽  
Computational Method ◽  
Support Vector ◽  
Feature Subset ◽  
Feature Selection Technique

Owing to the abuse of antibiotics, drug resistance of pathogenic bacteria becomes more and more serious. Therefore, it is interesting to develop a more reasonable way to solve this issue. Because they can destroy the bacterial cell structure and then kill the infectious bacterium, the bacterial cell wall lyases are suitable candidates of antibacteria sources. Thus, it is urgent to develop an accurate and efficient computational method to predict the lyases. Based on the consideration, in this paper, a set of objective and rigorous data was collected by searching through the Universal Protein Resource (the UniProt database), whereafter a feature selection technique based on the analysis of variance (ANOVA) was used to acquire optimal feature subset. Finally, the support vector machine (SVM) was used to perform prediction. The jackknife cross-validated results showed that the optimal average accuracy of 84.82% was achieved with the sensitivity of 76.47% and the specificity of 93.16%. For the convenience of other scholars, we built a free online server calledLypred. We believe thatLypredwill become a practical tool for the research of cell wall lyases and development of antimicrobial agents.

scholarly journals Plant thionins: structure, biological functions and potential use in biotechnology

2018 ◽  
Vol 22 (6) ◽  
pp. 667-675 ◽  
Author(s):  
T. I. Odintsova ◽  
M. P. Slezina ◽  
E. A. Istomina
Keyword(s):  
Pathogenic Bacteria ◽  
Plant Pathogens ◽  
Biological Activities ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Lipid Transfer ◽  
Human Pathogens ◽  
Candida Spp ◽  
Wide Range ◽  
Bacteria And Fungi

Antimicrobial peptides (AMPs) are important components of defense system in both plants and animals. They represent an ancient mechanism of innate immunity providing rapid first line of defense against pathogens. Plant AMPs are classified into several families: thionins, defensins, nonspecific lipid-transfer proteins, hevein- and knottin-type peptides, hairpinins and macrocyclic peptides (cyclotides). The review focuses on the thionin family. Thionins comprise a plant-specific AMP family that consists of short (~5 kDA) cysteine-rich peptides containing 6 or 8 cysteine residues with antimicrobial and toxic properties. Based on similarity in amino acid sequences and the arrangement of disulphide bonds, five structural classes of thionins are discriminated. The three-dimensional structures of a number of thionins were determined. The amphipathic thionin molecule resembles the Greek letter Г, in which the long arm is formed by two antiparallel α-helices, while the short one, by two parallel β-strands. The residues responsible for the antimicrobial activity of thionins were identified. Thionins are synthesized as precursor proteins consisting of a signal peptide, the mature peptide region and the C-terminal prodomain. Thionins protect plants from pathogenic bacteria and fungi acting directly on the membranes of microorganisms at micromolar concentrations, although their precise mode of action remains unclear. In addition to plant pathogens, thionins inhibit growth of a number of human pathogens and opportunistic microorganisms, such as Candida spp., Saccharomyces cerevisiae, Fusarium solani, Staphylococcus aureus and Escherichia coli. Thionins are toxic to different types of cells including mammalian cancer cell lines. Transgenic plants expressing thionin genes display enhanced resistance to pathogens. A wide range of biological activities makes thionins promising candidates for practical application in agriculture and medicine.

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 Carcass Salmonella and Its Drug Resistance

2019 ◽  
pp. 1-21
Author(s):  
Gizachew Muluneh Amera ◽  
Amit Kumar Singh
Keyword(s):  
Public Health ◽  
Antimicrobial Resistance ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Personal Hygiene ◽  
Wide Range ◽  
Food Animals

Salmonella are the major pathogenic bacteria in humans as well as in animals. Salmonella species are leading causes of acute gastroenteritis in several countries and salmonellosis remains an important public health problem worldwide, particularly in the developing countries. Isolation of Salmonella from a wide range of sources suggests that Salmonella is widespread in food animals and meat products and underlines the necessity for a joint and coordinated surveillance and monitoring programs for salmonellosis and other major food borne zoonotic diseases. Food animals harbor a wide range of Salmonella and so act as sources of contamination, which is of paramount epidemiological importance in non-typhoid human salmonellosis. Salmonellosis is more aggravated by the ever increasing rate of antimicrobial resistance strains in food animals. The high prevalence and dissemination of multidrug resistant (MDR) Salmonella have become a growing public health concern. Multidrug resistant (MDR) strains of Salmonella are now encountered frequently and the rates of multidrug resistance have increased considerably in recent years. Food animal consumption is a potential cause for antimicrobial resistant Salmonella illnesses besides, the common factors such as overcrowding, poverty, inadequate sanitary conditions, and poor personal hygiene. Practicing good sanitary measures, extensive education programs for proper hygiene and improvement of managements are solutions to eliminate the high bacteriological load as well as prevalence of Salmonella in cattle carcass. Furthermore, restricting the use of antimicrobial agents in food animals, designation of multidrug-resistant Salmonella as an adulterant in ground beef, improving the mechanisms for product trace-back investigations and wise and discriminate use of antimicrobials should be practiced to combat the ever increasing situation of antimicrobial resistance. So, this review used for updating information on their prevalence and resistance patterns is very important to suggest the acceptance of the carcass in relation to the standards and for proper selection and use of antimicrobial agents in a setting.

scholarly journals Bacterial Contaminants on Exposed Surfaces and Their Antibiotic Sensitivity Patterns at the Benjamin Mkapa Hospital, Dodoma-Tanzania

2021 ◽  
pp. 1-11
Author(s):  
Alphonce B. Chandika ◽  
Reuben S. Mkala ◽  
Bushi Lugoba ◽  
Benjamin C. Kipilipili ◽  
Witness Saitot ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Antibiotic Sensitivity ◽  
Surgical Site Infections ◽  
Healthcare Services ◽  
Control Measures ◽  
Hospital Environment ◽  
Infection Prevention And Control ◽  
Bacterial Isolates ◽  
Wide Range

Background: Hospital acquired infection pose a great challenge in provision of healthcare services to many settings  particulary in developing countries where there is limited availability of resources. The roles played by exposed surfaces in spreading of potential bacterial pathogens within the hospital environment have certainly contributed to the increased burden of bacterial infectious diseases such as morbidness, death as well as cost imolecation in healthcare. Our study aimed to determine common bacteria isolated on exposed surfaces and the antimicrobial sensitivity patterns. Methods: A sum of 516 specimens gathered and enrolled for study at Benjamin Mkapa Hopsital (BMH).  The swab specimens were continuously gathered (collected) from different exposed objects in hospital environmental surfaces. All microbiological procedures or tests were performed using appropriate standard operating procedure. The obtained data were analysed using SPSS version 16.0. Results: Among 516 samples, 317 (61.4%) were positive with variety of bacterial isolates from different sites. Out of 317 positive cultures, 120 (37.9%) Staphylococcus aureus, 97 (30.6%) E. coli, 28 (8.8%) Enterobacter aerogenes, 25 (7.9%) Pseudomonas aeruginosa, 23 (7.3%) other Citrobacter species, 20 (6.3%) Citrobacter freundii, 3 (0.9%) Morganella morganii and 1 (0.3%) Serratia mercesens were isolated from different source of exposed surfaces at BMH. Serratia mercesens were highly (100%) resistant to most of the antimicrobial agents including erythromycin, cefotaxime, ciprofloxacin, gentamicin, amikacin, penicillin,ceftriaxone, ceftazidime, levofloxacin, ampicillin, azithromycin and cotrimoxazoleTrimethoprim/sulfamethoxazole. Conclusion: High levels of potentially pathogenic bacteria were isolated in swab specimens from a wide range of exposed surfaces at BMH. Variable pattern of antiobiotic resistance were observed among bacterial isolates with alarming levels demonstrated by isolates of Serratia mercesens which is amongst the common causes of surgical site infections. This findings call for improved actions for infection prevention and control measures at BMH.

scholarly journals Isolation of Bacteriophage from Eggs and Use of Excreta as Biocontrol Agent in Controlling Eggs Related Salmonellosis

2019 ◽  
Vol 35 (1) ◽  
pp. 37-44
Author(s):  
Md Abu Sayem Khan ◽  
Md Muktadir Rahman Ashik ◽  
Sabita Rezwana Rahman
Keyword(s):  
Salmonella Enteritidis ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Penicillin G ◽  
Biochemical Tests ◽  
Salmonella Spp ◽  
Antibiotic Resistant ◽  
Poultry Products ◽  
Wide Range ◽  
Agar Layer

Poultry and poultry products are the leading causes of foodborne salmonellosis worldwide. Antibiotics are used to control Salmonella spp. in poultry but its uncontrolled use results in the emergence of resistant pathogens.The use of bacteriophages as antimicrobial agents to control antibiotic resistant pathogenic bacteria could be a possible alternative. The aim of this study was to isolate, characterize and evaluate the effectiveness of bacteriophages for reducingload of Salmonella spp. on eggshells. One bacteriophage named as Sal-PE, specific to Salmonella enteritidiswas isolated from poultry excreta. For isolation, samples were subject to an enrichment protocol and then double agar layer method was performed to detect plaque. It had the capability to survive in wide range of pH between 4 to 10and found to be resistant at 60°C for 1 hour. Sal” PE showed its lytic effect on 13 of the 15 (87%) isolates including Salmonella enteritidis and Salmonella typhimurium which were recovered from 50 poultry excreta samples. After enrichment and growth on selective media, isolates were identified based on cultural characteristics, microscopic observation and biochemical tests. Amplification of three different genes (invA, sdfI, fliC) were carried out tocharacterize those isolates in molecular level. All isolates were found to be resistant to penicillin G, ampicillin, oxacillin and clindamycin but sensitive to ciprofloxacin, streptomycin, cefixime and chloramphenicol. Lytic efficiency of Sal-PE was determined by observing the reduction in optical density due to destruction of pathogens. Though more studies are needed in order to evaluate phage effectiveness, our findingsare expected to help us in initiating the development of a better preventive approach to control the occurrence of Salmonella spp. on eggshells. Bangladesh J Microbiol, Volume 35 Number 1 June 2018, pp 37-44

Antimicrobial effect of phenazines produced by Pseudomonas aeruginosa isolated from saline soil of Mina River, Algeria

2016 ◽  
Vol 5 (5) ◽  
pp. 187-193
Author(s):  
Hicham Dahah ◽  
Rachid Djibaoui ◽  
Saïd Nemmiche
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Saline Soil ◽  
Antimicrobial Effect ◽  
Diffusion Method ◽  
Gel Chromatography ◽  
Minimal Inhibitory Concentrations ◽  
River Region ◽  
Wide Range

Several strains of environmental Pseudomonas aeruginosa have been used in biotechnology to produce beneficial metabolites in medicine and agriculture. Many secondary metabolites are secreted throughout their growth where phenazines are one among the most known stronger metabolites. The phenazines are antimicrobial substances inhibiting a wide range of pathogenic bacteria. In order to exploit the antimicrobial effect of P. aeruginosa and its pheanzines we do isolate the studied bacteria from saline soil collected from Mina river region (Relizane, Algeria). Ten isolates belonged to Pseudomonas were selected by an antagonistic test, one of isolates was identified as P. aeruginosa and selected for phenazines production. Phenazines were produced using King A broth medium, extracted by ethyl acetate and purified by silica gel chromatography. The antimicrobial activity of crude extract containing phenazines was evaluated by the disc diffusion method against a number of pathogen microorganisms and the minimal inhibitory concentrations (MIC) were determined. The results indicated that the crude phenazines solution was effective against Escherichia coli, Staphylococcus aureus, Bacillus cereus, Shigella sonnei and Candida albicans. The characterization of purified phenazines extract by HPLC showed a peak similar to the standard. The results of this study will contribute in the identification of the potential of phenazines naturally-occurring substances as antimicrobial agents.

Peptidoglycan Deacetylases in Bacterial Cell Wall Remodeling and Pathogenesis

2021 ◽  
Vol 28 ◽  
Author(s):  
Antoni Planas
Keyword(s):  
Cell Wall ◽  
Bacterial Cell ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Biochemical Characterization ◽  
Dynamic Structure ◽  
Bacterial Cell Wall ◽  
Innate Immune ◽  
Functional Roles ◽  
Bacterial Division

: The bacterial cell wall peptidoglycan (PG) is a dynamic structure that is constantly synthesized, re-modeled and degraded during bacterial division and growth. Post-synthetic modifications modulate the action of endogenous autolysis during PG lysis and remodeling for growth and sporulation, but also they are a mechanism used by pathogenic bacteria to evade the host innate immune system. Modifica-tions of the glycan backbone are limited to the C-2 amine and the C-6 hydroxyl moieties of either Glc-NAc or MurNAc residues. This paper reviews the functional roles and properties of peptidoglycan de-N-acetylases (distinct PG GlcNAc and MurNAc deacetylases) and recent progress through genetic stud-ies and biochemical characterization to elucidate their mechanism of action, 3D structures, substrate specificities and biological functions. Since they are virulence factors in pathogenic bacteria, peptidogly-can deacetylases are potential targets for the design of novel antimicrobial agents.

scholarly journals An Engineered Multimodular Enzybiotic against Methicillin-Resistant Staphylococcus aureus

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1384
Author(s):  
Salim Manoharadas ◽  
Mohammad Altaf ◽  
Abdulwahed Fahad Alrefaei ◽  
Naushad Ahmad ◽  
Shaik Althaf Hussain ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Binding Domain ◽  
Strong Activity ◽  
Methicillin Resistant ◽  
Cell Wall Binding ◽  
Cell Wall Binding Domain

Development of multidrug antibiotic resistance in bacteria is a predicament encountered worldwide. Researchers are in a constant hunt to develop effective antimicrobial agents to counter these dreadful pathogenic bacteria. Here we describe a chimerically engineered multimodular enzybiotic to treat a clinical isolate of methicillin-resistant Staphylococcus aureus (S. aureus). The cell wall binding domain of phage ϕ11 endolysin was replaced with a truncated and more potent cell wall binding domain from a completely unrelated protein from a different phage. The engineered enzybiotic showed strong activity against clinically relevant methicillin-resistant Staphylococcus aureus. In spite of a multimodular peptidoglycan cleaving catalytic domain, the engineered enzybiotic could not exhibit its activity against a veterinary isolate of S. aureus. Our studies point out that novel antimicrobial proteins can be genetically engineered. Moreover, the cell wall binding domain of the engineered protein is indispensable for a strong binding and stability of the proteins.

Preliminary in Vitro Investigations on The Inhibitory Activity of The Original Dietary Supplement Oxidal® on Pathogenic Bacterial Strains

2020 ◽  
Vol 11 ◽  
pp. 37-43
Author(s):  
Prof. Teodora P. Popova ◽  
Toshka Petrova ◽  
Ignat Ignatov ◽  
Stoil Karadzhov
Keyword(s):  
Dietary Supplement ◽  
Broad Spectrum ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Clinical Effectiveness ◽  
Inhibitory Effect ◽  
Diffusion Method ◽  
Bacterial Strains ◽  
Microbial Strains

The antimicrobial action of the dietary supplement Oxidal® was tested using the classic Bauer and Kirby agar-gel diffusion method. Clinical and reference strains of Staphylococcus aureus and Escherichia coli were used in the studies. The tested dietary supplement showed a well-pronounced inhibitory effect against the microbial strains commensurable with that of the broad-spectrum chemotherapeutic agent Enrofloxacin and showed even higher activity than the broad spectrum antibiotic Thiamphenicol. The proven inhibitory effect of the tested dietary supplement against the examined pathogenic bacteria is in accordance with the established clinical effectiveness standards for antimicrobial agents.

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