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

Author(s):  
Mukil Sunil ◽  
A. S. Smiline Girija ◽  
P. Sankar Ganesh ◽  
J. Vijayashree Priyadharshini

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.

2021 ◽  
Vol 11 ◽  
Author(s):  
Lida Chen ◽  
Pinghai Tan ◽  
Jianming Zeng ◽  
Xuegao Yu ◽  
Yimei Cai ◽  
...  

BackgroundThis study aimed to examine the impact of an intervention carried out in 2011 to combat multi-drug resistance and outbreaks of imipenem-resistant Acinetobacter baumannii (IRAB), and to explore its resistance mechanism.MethodsA total of 2572 isolates of A. baumannii, including 1673 IRAB isolates, were collected between 2007 and 2014. An intervention was implemented to control A. baumannii resistance and outbreaks. Antimicrobial susceptibility was tested by calculating minimal inhibitory concentrations (MICs), and outbreaks were typed using pulsed-field gel electrophoresis (PFGE). Resistance mechanisms were explored by polymerase chain reaction (PCR) and whole genome sequencing (WGS).ResultsFollowing the intervention in 2011, the resistance rates of A. baumannii to almost all tested antibiotics decreased, from 85.3 to 72.6% for imipenem, 100 to 80.8% for ceftriaxone, and 45.0 to 6.9% for tigecycline. The intervention resulted in a decrease in the number (seven to five), duration (8–3 months), and departments (five to three) affected by outbreaks; no outbreaks occurred in 2011. After the intervention, only blaAMPC (76.47 to 100%) and blaTEM–1 (75.74 to 96.92%) increased (P < 0.0001); whereas blaGES–1 (32.35 to 3.07%), blaPER–1 (21.32 to 1.54%), blaOXA–58 (60.29 to 1.54%), carO (37.50 to 7.69%), and adeB (9.56 to 3.08%) decreased (P < 0.0001). Interestingly, the frequency of class B β-lactamase genes decreased from 91.18% (blaSPM–1) and 61.03% (blaIMP–1) to 0%, while that of class D blaOXA–23 increased to 96.92% (P < 0.0001). WGS showed that the major PFGE types causing outbreaks each year (type 01, 11, 18, 23, 26, and 31) carried the same resistance genes (blaKPC–1, blaADC–25, blaOXA–66, and adeABC), AdeR-S mutations (G186V and A136V), and a partially blocked porin channel CarO. Meanwhile, plasmids harboring blaOXA–23 were found after the intervention.ConclusionThe intervention was highly effective in reducing multi-drug resistance of A. baumannii and IRAB outbreaks in the long term. The resistance mechanisms of IRAB may involve genes encoding β-lactamases, efflux pump overexpression, outer membrane porin blockade, and plasmids; in particular, clonal spread of blaOXA–23 was the major cause of outbreaks. Similar interventions may also help reduce bacterial resistance rates and outbreaks in other hospitals.


Author(s):  
Zahra Davoudi ◽  
Amirhossein Taromchi ◽  
Bahram Kazemi ◽  
Mojgan Bandehpour ◽  
Nariman Mosaffa

Background and Objectives: Immunization is a promising strategy to combat against the life-threatening infections by Multi Drug Resistance Acinetobacter baumannii. In this study, we directed to design and evaluate the efficacy of a recombi- nant multi-epitope protein against this pathogen. Materials and Methods: Epitopes prediction was performed for candidate proteins OmpA and BAM complex (BamA, BamB, BamC, BamD, BamE) from A. baumannii, using immune-informatics tools with high affinity for the human HLA alleles. After expression and purification of the recombinant protein, its functional activity was confirmed by interaction with positive sera. Results: Cloning and expression of the desired multi-epitopes protein were verified. Circular Dichroism study showed the secondary structure and proper refolding of the recombinant protein was achieved and matched with computational predic- tion. There was a significant interaction between designed protein with antibodies presented in ICU patients' and staff's sera. Conclusion: The interaction of the recombinant protein with patients' sera antibodies suggests that it may be a promising determinant protein for immunization against of MDR A. baumannii.


Author(s):  
M. I. Sheefaa ◽  
A. S. Smiline Girija ◽  
P. Sankar Ganesh ◽  
J. Vijayashree Priyadharshini

Background: Acinetobacter baumannii is a gramnegative bacilli acquiring both intrinsic and adaptive patterns of multi drug resistance and virulence. Immune-informatics approach holds promise to detect putative epitope peptides from vital virulence factors which can be further synthesized and evaluated for their immunological response. Aim: The aim of the study was to predict the immuno-dominant peptides from the ptk gene of A. baumannii. Materials and Methods: Protein retrieval of the Ptk gene using CELLO V.2.5 was done with the evaluation of antigenicity and allergenicity of the predicted epitopes, using Vaxijen V2.0 server and AlgPred servers. Epitope structure prediction and validation by using RAMPAGE revealed the homology peptides. Molecular Docking of epitopes with HLA-alleles using ClusterPro server, and further identification of B cell epitope was performed by using Kolaskar and Tonganokar antigenicity method. Results: A total of 20 epitopes were predicted and 18 peptides were chosen based on antigenicity and stability analysis prediction. The structure predictions were carried out using pepfold server and based on Ramachandran plot analysis 10 epitopes were taken for further analysis. Conclusion: The present finding has detected and evaluated the desirable epitope as LFFSLIAQW using an immune-informatic approach. However, it needs further experimental validation for its immunological response using standard in-vitro studies.


Author(s):  
V. Thiru Kumaran ◽  
A. S. Smiline Girija ◽  
P. P. Sankar Ganesh ◽  
J. Vijayashree Priyadharshini

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.


2020 ◽  
Author(s):  
Saeedeh Ebrahimi ◽  
Behnam Sisakhtpour ◽  
Arezoo Mirzaei ◽  
Vajihe Karbasizadeh ◽  
Sharareh Moghim

Abstract Objective: Acinetobacter baumannii is responsible for most nosocomial infections in hospitals. It has the ability to form biofilms and has a high degree of antibiotic resistance. Colistin is one of the last therapeutic options for the treatment of Multi Drug Resistance infections. Recently, strains of this pathogen resistance to the colistin were reported increasingly. Therefore, alternative antibacterial methods such as phage therapy are being researched. Results: From 15 MDR A. baumannii clinical isolates, 26.6% were resistant to colistin, 80% were able to produce strong biofilm, and 20% produce weak biofilm. The isolated lytic phage (IsfAB78) was able to reduce the biofilm by up to 87%. Since most of the MDR colistin-resistant strains produce biofilm, and MDR A. baumannii infections are difficult to treat, development of phage therapy could be an alternative in the future. Phage IsfAB78 is a good candidate for this purpose.


Author(s):  
M. Kamalli ◽  
A. S. Smiline Girija ◽  
P. Sankar Ganesh ◽  
J. Vijayashree Priyadharsini

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.


2019 ◽  
Vol 7 (4) ◽  
pp. 132-137
Author(s):  
Zainab H. Abdullah ◽  
Narmin S. Merza

Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen and one of the most importnat Multidrug resistant microorganisms responsible for a vast array of nosocomial infections. 41 (6.8 %) isolates of A.  baumannii were obtained from a total of 603 clinical samples of burn and sputum during the period from March 2018 to February 2019. Twenty two isolates (3.6%) of A. baummanni were recovered from burn infections and nineteen isolates (3.2%) from sputum specimens. Identification and characterization of these isolates was accomplished by the aid of selective media (CHROM agar Acinetobacter) and was finally confirmed by VITEK 2 identification system test. Molecular identification utilizing genus and species-specific primers to detect the 16S rRNA and blaOXA-51 was also applied.  The Antibiotic resistance testing was done by the Kirby-Bauer disc diffusion method, 24 .4% of the isolates were Multi-Drug Resistance (MDR), while 65.9% were extensive drug resistance (XDR). All isolates  were absolutely resistant (100 %) to most of the antibiotics in use: cefixime, cefotaxime, ceftriaxone, ceftazidime, piperacillin-tazobactam, amoxicillin-tazobactam, while the resistant profile for the other antibiotics can be represented as follows 98 %, 95 %, 90 %, and 83 % For both ciprofloxacin and norfloxacin, gentamycin and meropenem, amikacin, and azithromycin and imipenem, respectively. On the other hand, levofloxacin has a moderate effect on the isolates shown by 51% resistant isolates followed by doxycycline for which 39% of the isolates were resistant. Colistin was the only antimicrobial agent that has an intense effect as the majority of the isolates were sensitive. All the selected isolates of A. baumannii were successfuly produced band corresponded to the intended genes. Accurate and early detection of such bacteria is essential for stimulates effective treatment specifically in intensive care units. Molecular techniques have been successfully applied with high specificity using 16S rRNA and blaOXA-51-like gene as a simple and reliable method to differentiate  A. baumannii strains.


2021 ◽  
Vol 1 (3) ◽  
pp. 403-411
Author(s):  
Mhd. Alzaref ◽  
Linosefa Linosefa ◽  
Gestina Aliska

Acinetobacter baumannii is such a big challenge in this modern era because of their multi-drug resistance (MDR) through their resistance mechanism, namely the production of beta lactamase enzymes, one of them is oxacillinases. Several studies have revealed that the OXA-23 gene has an important role in the production of the beta lactamase enzyme so that these bacteria are resistant to antibiotics, especially carbapenem. This study was conducted to determine the description of the resistance of the Acinetobacter baumannii by looking at the prevalence of the OXA-23 gene in clinical isolates of these bacteria at RSUP Dr. M. Djamil Padang. This study was a descriptive observational study and used a cross-sectional design using polymerase chain reactions (PCR) and electrophoresis techniques. The samples were clinical isolates of Acinetobacter baumannii bacteria stored in the Microbiology Laboratory of the Faculty of Medicine, Andalas University with inclusion and exclusion criteria. Of the 150 clinical isolates of Acinetobacter baumannii studied, most of the bacteria were still sensitive to the antibiotics of Amikacin (84%), Tigecycline (78.76%), and Trimethoprim / Sulfamethoxazole (76.77%). Meanwhile, all of the Acinetobacter baumannii isolates were resistant to cefazolin. In PCR and electrophoresis tests, 50 clinical isolates were positive for the OXA-23 gene. 46 of them were carbapenem resistant, while the other 4 isolates were sensitive to carbapenem. From these results it can be concluded that the prevalence of the OXA-23 gene in Acinetobacter baumannii isolates in RSUP Dr. M. Djamil Padang was 85.18% for carbapenem resistant isolates and 4.30% for carbapenem sensitive isolates. Keywords : Acinetobacter baumannii, carbapenem, OXA-23 gene


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