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Partial sequence alignment of ompA gene from the present study (Ab) with reference sequences available in the database. The deleted regions are depicted as dashes (–), mismatch as gap () and conserved sequences as star (*)
Source publication
The present study was conducted to molecularly characterize the biofilm associated ompA gene from the drug resistant strains of A. baumannii and its immuno-dominant vaccine epitope predictions through immuno-informatic approach. ompA was amplified by PCR from the genomic DNA and was sequenced. Using the ORF, ompA protein sequence was retrieved and...
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Background: Known as the vital avian disease in Indonesia, Newcastle disease (ND) has surged all over Indonesia which cause an immense drop in poultry industry. This investigation intended to examine the pathological and molecular characteristics of the latest Newcastle disease virus (NDV) derived from Gallus gallus in Java, Indonesia.Methods: The...
Citations
... Similarly, members of the OmpA family are essential OMPs, which have been widely studied in Acinetobacter baumanni [40], Mannheimia haemolytica, E. coli [41], Haemophilus species, and others [42,43]. In general, OmpA-like proteins sense and respond to external stimuli or stressors [44]. ...
Fusobacterium necrophorum, an anaerobic Gram-negative pathogen, causes necrotic cattle infections, impacting livestock health and the US feedlot industry. Antibiotic administration is the mainstay for treating F. necrophorum infections, although resistance hampers their effectiveness. Vaccination, especially targeting outer membrane proteins (OMPs) due to their antigenic properties and host specificity, offers an alternative to antibiotics. This study identified high-binding-affinity adhesion proteins from F. necrophorum using binding and pull-down assays with bovine adrenal gland endothelial cells (EJG). Four OMP candidates (17.5 kDa/OmpH, 22.7 kDa/OmpA, 66.3 kDa/cell surface protein (CSP), and a previously characterized 43 kDa OMP) were expressed as recombinant proteins and purified. Rabbit polyclonal antibodies to recombinant OMPs were generated, and their ability to inhibit bacterial binding in vitro was assessed. The results show that treatment with individual polyclonal antibodies against 43 kDa significantly inhibited bacterial adhesion, while other antibodies were less potent. However, combinations of two or more antibodies showed a more prominent inhibitory effect on host-cell adhesion. Thus, our findings suggest that the identified OMPs are involved in fusobacterial attachment to host cells and may have the potential to be leveraged in combination for vaccine development. Future in vivo studies are needed to validate their roles and test the feasibility of an OMP-based subunit vaccine against fusobacterial infections.
... Here, we aimed to determine the antimicrobial effects of a methanolic crude extract from A. marmelos against VRE isolated from root caries. Because bioinformatic analysis of biocompounds to identify their targets can accelerate drug development [14], we used computational tools to evaluate potential drug-ligand interactions between the compounds, coumarin, xanthotoxol, imperatorin, aegeline, and marmeline, which were isolated from A. marmelos, against vanA. ...
Objectives
Enterococcus faecalis is a gram positive diplococci, highly versatile and a normal commensal of the gut microbiome. Resistance to vancomycin is a serious issue in various health-care setting exhibited by vancomycin resistant Enterococci (VRE) due to the alteration in the peptidoglycan synthesis pathway. This study is thus aimed to detect the VRE from the patients with root caries from the clinical isolates of E. faecalis and to evaluate the in-silico interactions between vanA and the Aegles marmelos bio-compounds.
Methods
E. faecalis was phenotypically characterized from 20 root caries samples and the frequency of vanA and vanB genes was detected by polymerase chain reaction (PCR). Further crude methanolic extracts from the dried leaves of A. marmelos was assessed for its antimicrobial activity. This is followed by the selection of five A. marmelos bio-compounds for the computational approach towards the drug ligand interactions.
Results
12 strains (60%) of E. faecalis was identified from the root caries samples and vanA was detected from two strains (16%). Both the stains showed the presence of vanA and none of the strains possessed vanB. Crude extract of A. marmelos showed promising antibacterial activity against the VRE strains. In-silico analysis of the A. marmelos bio-compounds revealed Imperatonin as the best compound with high docking energy (–8.11) and hydrogen bonds with < 140 TPSA (Topological polar surface area) and zero violations.
Conclusion
The present study records the VRE strains among the root caries with imperatorin from A. marmelos as a promising drug candidate. However the study requires further experimentation and validation.
... A study conducted by, Sogasu et al. suggested certain peptides in OmpA protein as promising epitope vaccine candidates against multi-drug resistant strains of A. baumannii [84]. In another study, Ren et al. proposed a recombinant multi-epitope assembly peptide vaccine construct including FilF and NucAb proteins and evaluated its immunogenicity and protective immunity in Balb/c mice [85]. ...
Acinetobacter baumannii is one of the major pathogenic ESKAPE bacterium, which is responsible for about more than 722,000 cases in a year, globally. Despite the alarming increase in multidrug resistance, a safe and effective vaccine for Acinetobacter infections is still not available. Hence in the current study, a multiepitope vaccine construct was developed using linear B cell, cytotoxic T cell, and helper T cell epitopes from the antigenic and well-conserved lipopolysaccharide assembly proteins employing systematic immunoinformatics and structural vaccinology strategies. The multi-peptide vaccine was predicted to be highly antigenic, non-allergenic, non-toxic, and cover maximum population coverage worldwide. Further, the vaccine construct was modeled along with adjuvant and peptide linkers and validated to achieve a high-quality three-dimensional structure which was subsequently utilized for cytokine prediction, disulfide engineering, and docking analyses with Toll-like receptor (TLR4). Ramachandran plot showed 98.3% of the residues were located in the most favorable and permitted regions, thereby corroborating the feasibility of the modeled vaccine construct. Molecular dynamics simulation for a 100 ns timeframe further confirmed the stability of the binding vaccine-receptor complex. Finally, in silico cloning and codon adaptation were also performed with the pET28a (+) plasmid vector to determine the efficiency of expression and translation of the vaccine. Immune simulation studies demonstrated that the vaccine could trigger both B and T cell responses and can elicit strong primary, secondary, and tertiary immune responses. The designed multi-peptide subunit vaccine would certainly expedite the experimental approach for the development of a vaccine against A. baumannii infection.
Graphical Abstract
... Due to increasing antibiotic resistance, Acinetobacter baumannii has gained researchers' attention [1]. Nowadays, this bacterium has become an important agent of nosocomial infections worldwide. ...
Increasing antibiotic resistance of Acinetobacter baumannii highlights the urgent need to develop an effective vaccine to combat it. Despite all efforts, no approved vaccine against this bacterium is on the market, and attempts are underway to find effective vaccines. Due to their surface exposure, outer membrane proteins (OMPs) are excellent vaccine targets. The extracellular loops of OMPs are highly immunogenic. Therefore, in the present study, we aimed to detect the conserved, exposed, and immunogenic linear B-cell epitopes among sixty-five OMPs available in 35 A. baumannii genomes deposited in the Vaxign database. According to defined criteria (allergenicity, antigenicity, and non-similarity to host), four linear B-cell epitopes were selected as immunogenic peptides. Epitope shuffling was performed to select the best arrangements of epitopes. We proposed six different multi-epitope vaccines consisting of two Naked arrangements, two loop-less C-lobe (LCL) structures, and two FliC-based targets. An LCL-based multi-epitope vaccine showed the best molecular docking score with human TLRs (TLR 1, 2, 4, and 5) and immune simulation results (Th1 cell population and IFN-γ, IL-12, IgM, IgG1, and IgG2 levels). This study provided a valuable library of exposed epitopes including 26 conserved linear immunogenic B-cell epitopes (belonged to 14 OMPs) and three optimized multi-epitope vaccines. However, more experimental studies are needed to confirm the actual immunoreactivity of vaccine candidates.
... Following transcriptional characterisation of A. baumannii Omp33-36 protein to highlight its role during the initial phase of infection, phylogenetic analyses have revealed an 8-aa highly conserved motif (PLAEAAFL), potential enough for vaccine development processing (83). Moreover, comparative genomics on A. baumannii OmpA of different strains, with downstream in silico prediction of T and B cell epitopes, as well as in silico characterisation and molecular docking with TLR-2, has derived a 25 amino acids long vaccine candidate by Sogasu et al. (84). Furthermore, another study has demonstrated the integration of pan genomic analysis of around 4200 genomes, T and B cell epitope predictions, and network-based centrality methods in identifying multiple immunologic nodes in A. baumannii, which can result in the elucidation of combinatorial synergy in different antigens for different vaccination strategies (85). ...
In parallel to the uncontrolled use of antibiotics, the emergence of multidrug-resistant bacteria, like Acinetobacter baumannii, has posed a severe threat. A. baumannii predominates in the nosocomial setting due to its ability to persist in hospitals and survive antibiotic treatment, thereby eventually leading to an increasing prevalence and mortality due to its infection. With the increasing spectra of drug resistance and the incessant collapse of newly discovered antibiotics, new therapeutic countermeasures have been in high demand. Hence, recent research has shown favouritism towards the long-term solution of designing vaccines. Therefore, being a realistic alternative strategy to combat this pathogen, anti-A. Baumannii vaccines research has continued unearthing various antigens with variable results over the last decade. Again, other approaches, including pan-genomics, subtractive proteomics, and reverse vaccination strategies, have shown promise for identifying promiscuous core vaccine candidates that resulted in chimeric vaccine constructs. In addition, the integration of basic knowledge of the pathobiology of this drug-resistant bacteria has also facilitated the development of effective multiantigen vaccines. As opposed to the conventional trial-and-error approach, incorporating the in silico methods in recent studies, particularly network analysis, has manifested a great promise in unearthing novel vaccine candidates from the A. baumannii proteome. Some studies have used multiple A. baumannii data sources to build the co-functional networks and analyze them by k-shell decomposition. Additionally, Whole Genomic Protein Interactome (GPIN) analysis has utilized a rational approach for identifying essential proteins and presenting them as vaccines effective enough to combat the deadly pathogenic threats posed by A. baumannii. Others have identified multiple immune nodes using network-based centrality measurements for synergistic antigen combinations for different vaccination strategies. Protein-protein interactions have also been inferenced utilizing structural approaches, such as molecular docking and molecular dynamics simulation. Similar workflows and technologies were employed to unveil novel A. baumannii drug targets, with a similar trend in the increasing influx of in silico techniques. This review integrates the latest knowledge on the development of A. baumannii vaccines while highlighting the in silico methods as the future of such exploratory research. In parallel, we also briefly summarize recent advancements in A. baumannii drug target research.
... In another study, out of 10 epitopes, 5 epitopes with high score were selected for further analysis of antigenicity. Out of 5 epitopes, 2 epitopes were predicted as probable antigens with the antigenic score of > 0.5 [58]. In another study, out of 10 epitopes, 3 epitopes were selected since it showed positive values [59]. ...
Background: Acinetobacter baumannii is an opportunistic bacterial pathogen that is primarily associated with hospital-acquired infections. Recently, there is a dramatic increase in the incidence of multidrug-resistant (MDR) strains, which has significantly raised the profile of this emerging opportunistic pathogen. MDR is often associated with the formation of biofilms and various other virulence factors. Amidst all the genes, fimH gene is our area of interest in this research, because it is an important virulence factor in A. baumannii which encodes the Type 1 fimbriae, that helps bacteria bind to the surface of host cells initiating further infection. Aim: The aim of this study was to assess the epitope based vaccine epitope peptide predictions for the fimH protein of A. baumannii. Materials and Methods: The fimH gene for epitope prediction was selected. Druggability and physico-chemical properties were analysed. Antigenicity was predicted. Epitope mapping of T-cell MHC class 1, Class 1 immunogenicity, conservancy and toxicity analysis was done. T-cell class II epitopes were further mapped together with the immuno-dominant B-cell epitopes. Results: From the selected 20 epitopes, 2 best epitopes (AALVASVCL and YSSGANAFT) were selected after analysing their antigenicity and allergenicity. The epitope YSSGANAFT showed better values in association with HLA alleles - HLA-DP, HLA-DQ, HLA-DR and TLR-2. Conclusion: The finding of the study documents a single immunodominant peptide (sequence) as a promising vaccine candidate to treat infections caused by A. baumannii. However further experimental analysis must be performed to assess the immunological memory and response of the peptide in both in-vitro and in-vivo studies.
... Computational based approaches seem to be of higher value in assessing the drug ligand interactions based docking studies. In a previous study, csgA protein of A.baumannii and the anti-biofilm activity of A.indica was assessed and predictions of epitope peptides against the virulent protein of A.baumanni has also been assessed [24,25]. However no earlier studies had documented the inhibitory effect of Ocimum sanctum biocompounds on ptk of A.baumannii. ...
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.
Linezolid is the first and only oxazolidinone antibacterial drug was approved in the last 35 years. It exhibits bacteriostatic efficacy against M. tuberculosis and is a crucial constituent of the BPaL regimen (Bedaquiline, Pretomanid, and Linezolid), which was authorized by the FDA in 2019 for the treatment of XDR-TB or MDR-TB. Despite its unique mechanism of action, Linezolid carries a considerable risk of toxicity, including myelosuppression and serotonin syndrome (SS), which is caused by inhibition of mitochondrial protein synthesis (MPS) and monoamine oxidase (MAO), respectively. Based on the structure toxicity relationship (STR) of Linezolid, in this work, we used a bioisosteric replacement approach to optimize the structure of Linezolid at the C-ring and/or C-5 position for myelosuppression and serotogenic toxicity. Extensive hierarchical multistep docking, drug likeness prediction, molecular binding interactions analyses, and toxicity assessment identified three promising compounds (3071, 7549 and 9660) as less toxic potential modulators of Mtb EthR protein. Compounds 3071, 7549 and 9660 were having the significant docking score of -12.696 Kcal/mol, -12.681 Kcal/mol and -15.293 Kcal/mol towards the Mtb EthR protein with less MAO-A and B affinity [compound 3071: MAO A (-4.799 Kcal/mol) and MAO B (-6.552 Kcal/mol); compound 7549: MAO A (> -2.00 Kcal/mol) and MAO B (> -2.00 Kcal/mol) and compound 9660: MAO A (> -5.678 Kcal/mol) and MAO B (> -6.537Kcal/mol) and none of them shown the Leukopenia as a side effect due to the Myelosuppression. The MD simulation results and binding free energy estimations correspond well with docking analyses, indicating that the proposed compounds bind and inhibit the EthR protein more effectively than Linezolid. The quantum mechanical and electrical characteristics were evaluated using density functional theory (DFT), which also demonstrated that the proposed compounds are more reactive than Linezolid.Communicated by Ramaswamy H. Sarma.
The diverse function of the moonlighting proteins in Acinetobacter baumannii is highly associated with its virulence that had spurred renewed attention in recent years. The existing and newly formed hypothetical moonlighting proteins, evolve without jeopardizing the structural constraints of their original roles. It is yet uncertain and undefined to lucidly describe the functions of the moonlighting proteins in A. baumannii albeit its overwhelming evidences on few proteins. This commentary thus highlights the expression and occurrence of potent moonlighting proteins in A. baumannii, rendering virulence to the strains and the reasons to target the same portraying an active arena of research.
