Chimeric vaccine designs against Acinetobacter baumannii using pan genome and reverse vaccinology approaches (original) (raw)
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Identification of Novel Vaccine Candidates against Multidrug-Resistant Acinetobacter baumannii
PLoS ONE, 2013
Acinetobacter baumannii is an emerging opportunistic bacterium associated with nosocomial infections in intensive care units. The alarming increase in infections caused by A. baumannii is strongly associated with enhanced resistance to antibiotics, in particular carbapenems. This, together with the lack of a licensed vaccine, has translated into significant economic, logistic and health impacts to health care facilities. In this study, we combined reverse vaccinology and proteomics to identify surface-exposed and secreted antigens from A. baumannii. Using in silico prediction tools and comparative genome analysis in combination with in vitro proteomic approaches, we identified 42 antigens that could be used as potential vaccine targets. Considering the paucity of effective antibiotics available to treat multidrug-resistant A. baumannii infections, these vaccine targets may serve as a framework for the development of a broadly protective multi-component vaccine, an outcome that would have a major impact on the burden of A. baumannii infections in intensive care units across the globe.
BMC Genomics, 2016
Background: Acinetobacter baumannii has emerged as a significant nosocomial pathogen during the last few years, exhibiting resistance to almost all major classes of antibiotics. Alternative treatment options such as vaccines tend to be most promising and cost effective approaches against this resistant pathogen. In the current study, we have explored the pan-genome of A. baumannii followed by immune-proteomics and reverse vaccinology approaches to identify potential core vaccine targets. Results: The pan-genome of all available A. baumannii strains (30 complete genomes) is estimated to contain 7,606 gene families and the core genome consists of 2,445 gene families (~32 % of the pan-genome). Phylogenetic tree, comparative genomic and proteomic analysis revealed both intra-and inter genomic similarities and evolutionary relationships. Among the conserved core genome, thirteen proteins, including P pilus assembly protein, pili assembly chaperone, AdeK, PonA, OmpA, general secretion pathway protein D, FhuE receptor, Type VI secretion system OmpA/MotB, TonB dependent siderophore receptor, general secretion pathway protein D, outer membrane protein, peptidoglycan associated lipoprotein and peptidyl-prolyl cis-trans isomerase are identified as highly antigenic. Epitope mapping of the target proteins revealed the presence of antigenic surface exposed 9-mer T-cell epitopes. Protein-protein interaction and functional annotation have shown their involvement in significant biological and molecular processes. The pipeline is validated by predicting already known immunogenic targets against Gram negative pathogen Helicobacter pylori as a positive control. Conclusion: The study, based upon combinatorial approach of pan-genomics, core genomics, proteomics and reverse vaccinology led us to find out potential vaccine candidates against A. baumannii. The comprehensive analysis of all the completely sequenced genomes revealed thirteen putative antigens which could elicit substantial immune response. The integration of computational vaccinology strategies would facilitate in tackling the rapid dissemination of resistant A.baumannii strains. The scarcity of effective antibiotics and the global expansion of sequencing data making this approach desirable in the development of effective vaccines against A. baumannii and other bacterial pathogens.
Frontiers in Cellular and Infection Microbiology
Nosocomial infections have become alarming with the increase of multidrug-resistant bacterial strains of Acinetobacter baumannii. Being the causative agent in ∼80% of the cases, these pathogenic gram-negative species could be deadly for hospitalized patients, especially in intensive care units utilizing ventilators, urinary catheters, and nasogastric tubes. Primarily infecting an immuno-compromised system, they are resistant to most antibiotics and are the root cause of various types of opportunistic infections including but not limited to septicemia, endocarditis, meningitis, pneumonia, skin, and wound sepsis and even urinary tract infections. Conventional experimental methods including typing, computational methods encompassing comparative genomics, and combined methods of reverse vaccinology and proteomics had been proposed to differentiate and develop vaccines and/or drugs for several outbreak strains. However, identifying proteins suitable enough to be posed as drug targets and/or molecular vaccines against the multidrug-resistant pathogenic bacterial strains has probably remained an open issue to address. In these cases of novel protein identification, the targets either are uncharacterized or have been unable to confer the most coveted protection either in the form of molecular vaccine candidates or as drug targets. Here, we report a strategic approach with the 3,766 proteins from the whole genome of A. baumannii ATCC19606 (AB) to rationally identify plausible candidates and propose them as future molecular vaccine candidates and/or drug targets. Essentially, we started with mapping the vaccine candidates (VaC) and virulence factors (ViF) of A. baumannii strain AYE onto strain ATCC19606 to identify them in the latter. We move on to build small networks of VaC and ViF to conceptualize their position in the network space of the whole genomic protein interactome (GPIN) and rationalize their candidature for drugs and/or molecular vaccines. To this end, we propose new sets of known proteins Mujawar et al. Vaccine Candidates and Drug Targets of A. baumannii unearthed from interactome built using key factors, KeF, potent enough to compete with VaC and ViF. Our method is the first of its kind to propose, albeit theoretically, a rational approach to identify crucial proteins and pose them for candidates of vaccines and/or drugs effective enough to combat the deadly pathogenic threats of A. baumannii.
The bacterial species Acinetobacter baumannii is a major cause of hospital acquired infection throughout the world and it is increasing public health concern. Infection caused by multidrug resistant A. baumannii is currently among the most difficult to treat due to propensity to acquire mobile genetic element. To date there is no vaccine or specific drug available for its treatment, this necessitate the need for the identification of therapeutic target enzyme and vaccine. Pharmacogenomic and computational biology represent an attractive alternative approach for the identification of common drug target and peptide-vaccine candidates in the pathogen. Vaccine designing is shifted from entire pathogen or whole antigen to peptide or epitope based-vaccines that are specific, safe and easy to produce. Comparative genomic approach was used to identify conserved protein signatures among five genomes. Three outer membrane proteins conserved among the genomes with high vaxijen scores were used to produce both B-cell and T-cell mediated immunity. Propred and propred1 were used to predict promiscuos helper T-Lymphocytes (HTL), Cytotoxic T-Lymphocyte (CTL) epitopes and MHCPred for their binding affinity.Three T-cell epitopes derived from identified B-cells bind to maximum number of MHC class I and class II alleles and specifically bind to HLA alleles such as DRB1*0101 and DRB1*0401.The epitopes are YEKLAAGPS, FYTSQPEDS and YVTGNPLGL with high potential to induce humoral and cell mediated immune responses. These predicted epitopes (small peptide) might be promising candidates for vaccine design against A. baumannii infection, though experimental validation.
Vaccinomics to Design a Multi-Epitopes Vaccine for Acinetobacter baumannii
International Journal of Environmental Research and Public Health
Antibiotic resistance (AR) is the result of microbes’ natural evolution to withstand the action of antibiotics used against them. AR is rising to a high level across the globe, and novel resistant strains are emerging and spreading very fast. Acinetobacter baumannii is a multidrug resistant Gram-negative bacteria, responsible for causing severe nosocomial infections that are treated with several broad spectrum antibiotics: carbapenems, β-lactam, aminoglycosides, tetracycline, gentamicin, impanel, piperacillin, and amikacin. The A. baumannii genome is superplastic to acquire new resistant mechanisms and, as there is no vaccine in the development process for this pathogen, the situation is more worrisome. This study was conducted to identify protective antigens from the core genome of the pathogen. Genomic data of fully sequenced strains of A. baumannii were retrieved from the national center for biotechnological information (NCBI) database and subjected to various genomics, immunoinf...
Asian Journal of Pharmaceutical and Clinical Research
Objective: Multiple drug resistance (MDR) in bacteria, particularly Gram-negative bacilli, has significantly hindered the treatment of infections caused by these bacteria. This results in the need for identifying new drugs and drug targets for these bacteria. The objective of this study was to identify novel drug targets in Acinetobacter baumannii which has emerged as a medically important pathogen due to an increasing number of infections caused by it and its MDR property.Methods: In our study, we implemented in silico subtractive genomics approach to identify novel drug targets in A. baumannii American type culture collection 17978. Various databases and online software were used to build a systematic workflow involving comparative genomics, metabolic pathways analysis, and drug target prioritization to identify pathogen-specific novel drug targets.Results: First, 458 essential proteins were retrieved from a database of essential genes, and by performing BLASTp against Homo sapie...
Promising Acinetobacter baumannii Vaccine Candidates and Drug Targets in Recent Years
Frontiers in Immunology, 2022
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.
Computationally designing antimicrobial peptides for Acinectobacter Baumannii
Acinetobacter Baumannii, which is mostly contracted in hospital stays, has been developing resistance to all available antibiotics, including the last line of drugs, such as carbapenem. Because of its quick adaptation there is an immediate need to design new antibiotics, possibly antimicrobial peptides (AMPs) to which bacteria do not develop resistance easily. Our threefold goal was to curate the available activity of AMPs on the same strain of A. Baumannii, build a neural network model for predicting their activity and use it to rationally pre-screen for lead generation from the thousands of naturally occurring AMPs. By curating and analyzing the recent activity data from 81 AMPs on ATCC 19606 strain, we develop a quantitative AMP activity prediction model. We selected three other models with comparable performance against a test set with known activities. With the goal of inspiring further studies on AMP drug candidates and their rational shortlisting, we made activity predictions...