scholarly journals A Computational Approach on the Anti-biofilm Effect of Ocimum sanctum Bio-compounds Against ptk of Acinetobacter baumannii

2021 ◽  
pp. 91-103
Author(s):  
M. Kamalli ◽  
A. S. Smiline Girija ◽  
P. Sankar Ganesh ◽  
J. Vijayashree Priyadharsini
Keyword(s):  
Binding Energy ◽  
Acinetobacter Baumannii ◽  
Protein Tyrosine Kinase ◽  
Capsular Polysaccharide ◽  
Opportunistic Pathogen ◽  
Inhibitory Effect ◽  
Computational Approach ◽  
Ocimum Sanctum ◽  
Docking Simulations ◽  
In Silico Docking

Introduction: Acinetobacter baumannii is a gram negative coccobacilli often considered as a nosocomial pathogen and as an opportunistic pathogen in immunocompromised patients. It is considered to be multi-drug resistant and a potent bacteria forming vital biofilms. Ptk which is protein tyrosine kinase is a protein coding gene involved with the synthesis of capsular polysaccharide. Ocimum sanctum is a perennial plant belonging to the Lamiaceae family. Tulsi and holy basil are the common names of this plant. In-silico docking approach method is much more convenient and cost effective to assess the bioactive properties of the natural drugs against any target ligands. Aim: The aim of the study to assess the inhibitory effect of Ocimum sanctum bio-compounds against ptk of Acinetobacter baumannii using a computational approach. Materials and Methods: Retrieval of the structure of ptk was followed by Ligand preparation and optimisation. Further drug likeliness was assessed using Molinspiration parameters, docking simulations and visualisation for the binding energy and hydrogen bonds. Results: Among the bio compounds of O.sanctum, benzofuran is selected as an active inhibitory compound with -11.12 as its binding energy showing a high affinity. Conclusion: The findings of the present study documents benzofuran as the promising candidate to design novel drugs from O.sanctum and to target the ptk of A.baumannii. However further experimental validation must be done to observe its efficacy and safety in the treatment of nosocomial infections caused by A.baumannii.

scholarly journals The K1 Capsular Polysaccharide of Acinetobacter baumannii Strain 307-0294 Is a Major Virulence Factor

2010 ◽  
Vol 78 (9) ◽  
pp. 3993-4000 ◽  
Author(s):  
Thomas A. Russo ◽  
Nicole R. Luke ◽  
Janet M. Beanan ◽  
Ruth Olson ◽  
Shauna L. Sauberan ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Drug Targets ◽  
Protein Tyrosine Kinase ◽  
Capsular Polysaccharide ◽  
Multidrug Resistant ◽  
Ascites Fluid ◽  
Infection Model ◽  
Flow Cytometric ◽  
K1 Capsule

ABSTRACT Acinetobacter baumannii is a pathogen of increasing medical importance with a propensity to be multidrug resistant, thereby making treatment challenging. Little is known of virulence traits in A. baumannii. To identify virulence factors and potential drug targets, random transposon (Tn) mutants derived from the A. baumannii strain AB307-0294 were screened to identify genes essential for growth in human ascites fluid in vitro, an inflammatory exudative fluid. These studies led to the identification of two genes that were predicted to be required for capsule polymerization and assembly. The first, ptk, encodes a putative protein tyrosine kinase (PTK), and the second, epsA, encodes a putative polysaccharide export outer membrane protein (EpsA). Monoclonal antibodies used in flow cytometric and Western analyses confirmed that these genes are required for a capsule-positive phenotype. A capsule-positive phenotype significantly optimized growth in human ascites fluid, survival in human serum, and survival in a rat soft tissue infection model. Importantly, the clearance of the capsule-minus mutants AB307.30 (ptk mutant, capsule minus) and AB307.45 (epsA mutant, capsule minus) was complete and durable. These data demonstrated that the K1 capsule from AB307-0294 was an important protectin. Further, these data suggested that conserved proteins, which contribute to the capsule-positive phenotype, are potential antivirulence drug targets. Therefore, the results from this study have important biologic and translational implications and, to the best of our knowledge, are the first to address the role of capsule in the pathogenesis of A. baumannii infection.

scholarly journals Effect of Azadirachta indica Bio-Compounds against KpsM Protein of Acinetobacter baumannii

2021 ◽  
pp. 773-780
Author(s):  
V. Thiru Kumaran ◽  
A. S. Smiline Girija ◽  
P. P. Sankar Ganesh ◽  
J. Vijayashree Priyadharshini
Keyword(s):  
Binding Energy ◽  
Acinetobacter Baumannii ◽  
Azadirachta Indica ◽  
Nosocomial Infections ◽  
In Silico ◽  
Experimental Studies ◽  
Docking Simulation ◽  
Docking Analysis ◽  
In Silico Docking ◽  
Selection Of

Background: Acinetobacter baumannii was considered as a low priority pathogen earlier, and is been now reported as a priority pathogen causing nosocomial infections. Selection of natural compounds to target the organism is the need of the hour. Aim: This study is aimed to target the KpsM protein of A. baumannii with the bio-compounds from Azadirachta indica using in-silico docking analysis. Materials and Methods: KpsM protein was retrieved and optimisation of protein was done. After that optimization and ligand preparation was carried out. It was continued by molinspiration assessment of the molecular properties of selected compounds. It was followed by docking simulation and docking visualisation. Results: Out of the 7 compounds of Azadirachta indica, dihydro diisoeugenol is the best compound to act on the KpsM protein of Acinetobacter baumannii and a binding energy of -6.83Kcal/Mol. Conclusion: The findings of the study reports isoeugenol with more binding energy than other compounds towards the selected protein KpsM of Acinetobacter baumannii. However it requires further experimental studies to understand the mechanism of its actions and safety.

scholarly journals Effect of Ocimum Sanctum Bio Compounds against csuE Gene Protein of Acinetobacter baumanii

2021 ◽  
pp. 117-125
Author(s):  
Mukil Sunil ◽  
A. S. Smiline Girija ◽  
P. Sankar Ganesh ◽  
J. Vijayashree Priyadharshini
Keyword(s):  
Drug Resistance ◽  
Acinetobacter Baumannii ◽  
Immunological Response ◽  
Multi Drug Resistance ◽  
Ocimum Sanctum ◽  
Acinetobacter Baumanii ◽  
Docking Analysis ◽  
In Silico Docking ◽  
Ligand Interactions ◽  
Alternative Medications

Background: Acinetobacter baumannii is a Gram-negative bacillus that is aerobic, pleomorphic and non-motile. Multi-drug resistance and biofilm formation contributes to the virulence and pathogenicity of the bacterium. Among many virulence factors, csuE is critical for initiation and assembly, showing much homology to type 1 and P pili. With much propensity of drug resistance, in recent years alternative medications have spurred renewed interest in targeting potent pathogens. Ocimum sanctum, also known as holy basil or tulsi possess various bio-active properties and can be used as alternative medicine to treat systemic ailments. Aim: This study was aimed to analyze the drug-ligand interactions between csuE protein of A. baumannii and the bio-compounds from O.sanctum using in-silico docking analysis. Material and Methods: csuE protein was retrieved and optimisation of protein was done. Ligands were selected and were assessed for drug likeness using molinspiration parameters. Further the compounds were subjected for docking analysis and the interacted molecules were visualized for binding energy and hydrogen bonds. Results: Out of the 9 compounds of Ocimum sanctum, benzofuran showed good interaction with csuE protein of Acinetobacter baumannii with a least docking energy of -5.31Kcal/Mol. Conclusion: The present study recommends benzofuran as the potent candidate for novel drug design to treat the infections caused by A.baumannii upon further evaluations for its safety and immunological response.

α-Glucosidase Inhibition, Antioxidant and Docking Studies of Hydroxycoumarins and their Mono and Bis O-alkylated/acetylated Analogs

2018 ◽  
Vol 15 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Parvesh Singh ◽  
Nomandla Ngcoya ◽  
Ramgopal Mopuri ◽  
Nagaraju Kerru ◽  
Neha Manhas ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Catalytic Site ◽  
Docking Simulations ◽  
In Silico Docking ◽  
Anti Oxidant

Background: Diabetes Mellitus (DM) is a complex metabolic disease illustrated by abnormally high levels of plasma glucose or hyperglycaemia. Accordingly, several α-glucosidase inhibitors have been developed for the treatment of diabetes and other degenerative disorders. While, a coumarin ring has the privilege to represent numerous natural and synthetic compounds with a wide spectrum of biological activities e.g. anti-cancer, anti-HIV, anti-viral, anti-malarial, anti-microbial, anti-convulsant, anti-hypertensive properties. Besides this, coumarins have also shown potential to inhibit α-glucosidase leading to a generation of new promising antidiabetic agents. However, the testing of O-substituted coumarins for α-glucosidase inhibition has evaded the attention of medicinal chemists. Methods: For O-alkylation/acetylation reactions, the hydroxyl coumarins (A-B) initially activated by K2CO3 in dry DMF were reacted with variedly substituted haloalkanes at room temperature under nitrogen. The synthesized compounds were tested for their α-glucosidase (from Saccharomyces cerevisiae) inhibitory activity and anti-oxidant activity using DPPH radical scavenging activity. In silico docking simulations were conducted using CDocker module in DS (Accelrys) to explore the binding modes of the representative compounds in the catalytic site of α-glucosidase. Results: All the coumarin analogues (A1, B1, A2-A10, B2-B8) including their precursors (A-B) were evaluated for their in vitro α-glucosidase inhibition using acarbose as a standard inhibitor. All the mono O-alkylated coumarins (except A1) showed significant (p <0.05) α-glucosidase inhibition relative to the hydroxyl coumarin (A) with IC50 values ranging between 11.084±0.117 to 145.24± 29.22 µg/mL. Compound 7-(benzyloxy)-4, 5-dimethyl-2H-chromen-2-one (A9) bearing a benzyl group (Ph-CH2-) at position 7 showed a remarkable (p <0.05) increase in the activity (IC50 = 11.084±0.117 µg/mL), almost four-fold more than acarbose (IC50 = 40.578±5.999 µg/mL). The introduction of –NO2 group dramatically improved the anti-oxidant activity of coumarin, while the O-alkylation/acetylation decreased the activity. Conclusion: The present study describes the synthesis of functionalized coumarins and their evaluation for α-glucosidase inhibition and antioxidant activity under in vitro conditions. Based on IC50 data, the mono O-alkylated coumarins were observed to be stronger inhibitors of α-glucosidase with respect to their bis O-alkylated analogues. Coumarin (A9) bearing O-benzyloxy group displayed the strongest α-glucosidase inhibition, even higher than the standard inhibitor acarbose. The coumarin (A10) bearing –NO2 group showed the highest anti-oxidant activity amongst the synthesized compounds, almost comparable to the ascorbic acid. Finally, in silico docking simulations revealed the role of hydrogen bonding and hydrophobic forces in locking the compounds in catalytic site of α-glucosidase.

scholarly journals Acinetobacter baumannii Infections in Hospitalized Patients, Treatment Outcomes

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 630
Author(s):  
Diaa Alrahmany ◽  
Ahmed F. Omar ◽  
Gehan Harb ◽  
Wasim S. El El Nekidy ◽  
Islam M. Ghazi
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Outcomes ◽  
Antibiotic Treatment ◽  
Financial Burden ◽  
Opportunistic Pathogen ◽  
Hospitalized Patients ◽  
Treatment Regimens ◽  
Serious Infections ◽  
Optimal Approach ◽  
Selection Of

Background Acinetobacter baumannii (AB), an opportunistic pathogen, could develop into serious infections with high mortality and financial burden. The debate surrounding the selection of effective antibiotic treatment necessitates studies to define the optimal approach. This study aims to compare the clinical outcomes of commonly used treatment regimens in hospitalized patients

scholarly journals Mutational analysis of genes implicated in LPS and capsular polysaccharide biosynthesis in the opportunistic pathogen Bacteroides fragilis

Microbiology ◽  
2009 ◽  
Vol 155 (4) ◽  
pp. 1039-1049 ◽  
Author(s):  
Sheila Patrick ◽  
Simon Houston ◽  
Zubin Thacker ◽  
Garry W. Blakely
Keyword(s):  
Capsular Polysaccharide ◽  
Mutational Analysis ◽  
Bacteroides Fragilis ◽  
Gene Clusters ◽  
Opportunistic Pathogen ◽  
Extracellular Polysaccharides ◽  
Phase Variable ◽  
Multiple Gene ◽  
Polysaccharide Biosynthesis ◽  
Group 1

The obligate anaerobe Bacteroides fragilis is a normal resident of the human gastrointestinal tract. The clinically derived B. fragilis strain NCTC 9343 produces an extensive array of extracellular polysaccharides (EPS), including antigenically distinct large, small and micro- capsules. The genome of NCTC 9343 encodes multiple gene clusters potentially involved in the biosynthesis of EPS, eight of which are implicated in production of the antigenically variable micro-capsule. We have developed a rapid and robust method for generating marked and markerless deletions, together with efficient electroporation using unmodified plasmid DNA to enable complementation of mutations. We show that deletion of a putative wzz homologue prevents production of high-molecular-mass polysaccharides (HMMPS), which form the micro-capsule. This observation suggests that micro-capsule HMMPS constitute the distal component of LPS in B. fragilis. The long chain length of this polysaccharide is strikingly different from classical enteric O-antigen, which consists of short-chain polysaccharides. We also demonstrate that deletion of a putative wbaP homologue prevents expression of the phase-variable large capsule and that expression can be restored by complementation. This suggests that synthesis of the large capsule is mechanistically equivalent to production of Escherichia coli group 1 and 4 capsules.

Structure of the capsular polysaccharide of Acinetobacter baumannii ACICU containing di-N-acetylpseudaminic acid

2014 ◽  
Vol 391 ◽  
pp. 89-92 ◽  
Author(s):  
Sof’ya N. Senchenkova ◽  
Alexander S. Shashkov ◽  
Mikhail M. Shneider ◽  
Nikolay P. Arbatsky ◽  
Anastasiya V. Popova ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Capsular Polysaccharide

scholarly journals Lon Protease Has Multifaceted Biological Functions inAcinetobacter baumannii

2018 ◽  
Vol 201 (2) ◽  
Author(s):  
Carly Ching ◽  
Brendan Yang ◽  
Chineme Onwubueke ◽  
David Lazinski ◽  
Andrew Camilli ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Developmental Process ◽  
Cell Envelope ◽  
Opportunistic Pathogen ◽  
Lon Protease ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Biofilm Development ◽  
Hospital Acquired

ABSTRACTAcinetobacter baumanniiis a Gram-negative opportunistic pathogen that is known to survive harsh environmental conditions and is a leading cause of hospital-acquired infections. Specifically, multicellular communities (known as biofilms) ofA. baumanniican withstand desiccation and survive on hospital surfaces and equipment. Biofilms are bacteria embedded in a self-produced extracellular matrix composed of proteins, sugars, and/or DNA. Bacteria in a biofilm are protected from environmental stresses, including antibiotics, which provides the bacteria with selective advantage for survival. Although some gene products are known to play roles in this developmental process inA. baumannii, mechanisms and signaling remain mostly unknown. Here, we find that Lon protease inA. baumanniiaffects biofilm development and has other important physiological roles, including motility and the cell envelope. Lon proteases are found in all domains of life, participating in regulatory processes and maintaining cellular homeostasis. These data reveal the importance of Lon protease in influencing keyA. baumanniiprocesses to survive stress and to maintain viability.IMPORTANCEAcinetobacter baumanniiis an opportunistic pathogen and is a leading cause of hospital-acquired infections.A. baumanniiis difficult to eradicate and to manage, because this bacterium is known to robustly survive desiccation and to quickly gain antibiotic resistance. We sought to investigate biofilm formation inA. baumannii, since much remains unknown about biofilm formation in this bacterium. Biofilms, which are multicellular communities of bacteria, are surface attached and difficult to eliminate from hospital equipment and implanted devices. Our research identifies multifaceted physiological roles for the conserved bacterial protease Lon inA. baumannii. These roles include biofilm formation, motility, and viability. This work broadly affects and expands understanding of the biology ofA. baumannii, which will permit us to find effective ways to eliminate the bacterium.

scholarly journals In Silico Docking and In Vitro Approaches towards BACE1 and Cholinesterases Inhibitory Effect of Citrus Flavanones

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1509 ◽  
Author(s):  
Seungeun Lee ◽  
Kumju Youn ◽  
GyuTae Lim ◽  
Jinhyuk Lee ◽  
Mira Jun
Keyword(s):  
In Silico ◽  
Inhibitory Effect ◽  
In Silico Docking

scholarly journals Enhanced Antibacterial Activity of Meropenem against Extensively Drug-Resistant Acinetobacter baumannii by Myrtaceae Plant Extracts

2020 ◽  
Vol 17 (11) ◽  
pp. 1168-1176
Author(s):  
Dennapa SAELOH ◽  
Monton VISUTTHI ◽  
Marisa LEEHA ◽  
Surasak LIMSUWAN ◽  
Supayang Piyawan VORAVUTHIKUNCHAI
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Drug Resistant ◽  
Microdilution Method ◽  
Extensively Drug Resistant ◽  
Resistant Phenotype ◽  
Bacterial Growth Inhibition ◽  
Mic Value

Acinetobacter baumannii (A. baumannii) has been known as a major cause of nosocomial bacterial infections worldwide. The bacteria are increasingly associated with a broad spectrum of antibiotic resistance, and this has become a widespread concern in a variety of hospitals.Antibiotic development and alternative treatment have become priorities for the treatment of bacterial infections.This study investigated the efficacy of meropenem in combination with five ethanolic extracts of plants in Myrtaceae against extensively drug-resistant (XDR) A. baumannii. The resistant phenotype was previously determined by microdilution method. XDR-A. baumannii strains showed resistance to meropenem with the minimum inhibitory concentration (MIC) in a range of 16 - 128 µg/mL, whereas the MIC value of all extracts, including Calistemon lancealatus, Eucalyptus citridora, Rhodomytus tomentasa, Syzygium cumini, and Xanthortemon chrysanthus, was over 1,000 µg/mL. Interestingly, all extracts potentiated the activity of the antibiotic by reducing the MIC values of the antibiotic. Xanthortemon chrysanthus extract displayed excellent synergism against the bacteria by decreasing the MIC value of the drug greater than 8-fold. In addition, the extract, at concentrations of 31.25, 62.5, 125, 250, 500, and 1,000 µg/mL, obviously increased the inhibitory effect of meropenem (1/4´MIC) against A. baumannii. The percentage of bacterial growth inhibition by combination was 87.9, 88.8, 91.8, 93.6, 99.9, and 100, respectively. The results supported that the extract could improve the activity of ineffective antibiotics against drug-resistant pathogens.Therefore, the findings may serve as therapeutic options for XDR-A. baumannii infections in the future.

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