<i>In Silico</i>Identification of Probable Drug and Vaccine Candidates Against Antibiotic-Resistant<i>Acinetobacter baumannii</i>

Hosseingholi, Elaheh Zadeh; Zarrini, Gholamreza; Pashazadeh, Marayam; Hayat, Seyed Mohammad Gheibi; Molavi, Ghader

doi:10.1089/mdr.2019.0236

Cited by 10 publications

(5 citation statements)

References 108 publications

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“…The aforementioned results underscored the importance of the pilus assembly system in the pathogenesis and immunogenicity of A. baumannii. Furthermore, the aforementioned data suggest that in silico approaches might be helpful in discovering likely drug and immunogenic candidates that have been ignored up to now (33).…”

Section: Discussionmentioning

confidence: 99%

In Silico Analyses of Extracellular Proteins of Acinetobacter baumannii as Immunogenic Candidates

et al. 2022

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Background: Acinetobacter baumannii is an important nosocomial pathogen causing high morbidity and mortality in immunocompromised patients with prolonged hospitalization. Multidrug-resistant A. baumannii infections are on the rise worldwide. Therefore, the discovery of an effective vaccine against this bacterium seems necessary as a cost-effective and preventive strategy. Methods: In this present study, 35 genomes of A. baumannii strains were considered, and the extracellular proteins were selected, maximally having one transmembrane helix with high adhesion probability and no similarity to host proteins, as immunogenic candidates using the web tool Vaxign. Subsequently, the role of these selected proteins in bacterial pathogenesis was investigated using VICMpred. Then, the major histocompatibility complex class II, linear B-cell epitopes, and conservation of epitopes were identified using the Immune Epitope Database, BepiPred, and Epitope Conservancy Analysis, respectively. Finally, the B-cell discontinuous epitopes of each protein were predicted using ElliPro and plotted on the three-dimensional structure (3D) of the proteins. The role of the unknown proteins was predicted using the STRING database. Results: In this study, eight acceptable immunogenic candidates, including FilF, FimA, putative acid phosphatase, putative exported protein, subtilisin-like serine protease, and three uncharacterized proteins, were identified in A. baumannii. Conclusions: The results of the STRING database showed that these three uncharacterized proteins play a role in nutrition (heme utilization), peptide bond cleavage (serine peptidases), and cellular processes (MlaD protein). Extracellular proteins might play a catalyst role in the outer membrane protein-based vaccine of A. baumannii. Furthermore, this study proposed a list of potent immunogenic candidates of extracellular proteins.

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Section: Discussionmentioning

confidence: 99%

In Silico Analyses of Extracellular Proteins of Acinetobacter baumannii as Immunogenic Candidates

et al. 2022

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“…By mapping small protein interactomes (SPIN) of virulent factors, vaccine candidates, and key factors retrieved from literature onto the whole genome protein interactome (GPIN), a study has reported crucial proteins via co-functional network analysis and k-shell decomposition, which can serve as potential vaccine candidates (22). Besides, a theoretical study on hypothetical proteins (HPs) in 30 multidrug-resistant A. baumannii strains has proposed 4 HPs as potential vaccine candidates via in silico immunological analyses (72). In addition, utilizing in silico functional analysis, the authors also proposed the druggability of 7 HPs.…”

Section: In-silico Methods In Driving Exploratory Research On Novel V...mentioning

confidence: 99%

Promising Acinetobacter baumannii Vaccine Candidates and Drug Targets in Recent Years

Tan

Lahiri

2022

Front. Immunol.

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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.

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“…Zadeh Hosseingholi et al. used bioinformatics analysis and found that four hypothetical proteins, HP4, HP6, HP8, and HP15, had the characteristics of vaccine candidates ( 131 ). Beiranvand et al.…”

Section: Candidate Subunit Vaccines For Acinetobacter Bauma...mentioning

confidence: 99%

“…Dcap-like protein and HP-2 have highly conserved surface-exposed epitopes (130). Zadeh Hosseingholi et al used bioinformatics analysis and found that four hypothetical proteins, HP4, HP6, HP8, and HP15, had the characteristics of vaccine candidates (131). Beiranvand et al used bioinformatics methods, reverse vaccinology, and subtractive genomics to select five vaccine candidates, namely, Pfsr, LptE, OmpH, CarO and FimF, which have appropriate antigenicity, solubility, and immunogenicity (57, 58).…”

Section: Novel Predicted Subunit Vaccine Candidate Proteinsmentioning

confidence: 99%

Subunit vaccines for Acinetobacter baumannii

et al. 2023

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Acinetobacter baumannii is a gram-negative bacterium and a crucial opportunistic pathogen in hospitals. A. baumannii infection has become a challenging problem in clinical practice due to the increasing number of multidrug-resistant strains and their prevalence worldwide. Vaccines are effective tools to prevent and control A. baumannii infection. Many researchers are studying subunit vaccines against A. baumannii. Subunit vaccines have the advantages of high purity, safety, and stability, ease of production, and highly targeted induced immune responses. To date, no A. baumannii subunit vaccine candidate has entered clinical trials. This may be related to the easy degradation of subunit vaccines in vivo and weak immunogenicity. Using adjuvants or delivery vehicles to prepare subunit vaccines can slow down degradation and improve immunogenicity. The common immunization routes include intramuscular injection, subcutaneous injection, intraperitoneal injection and mucosal vaccination. The appropriate immunization method can also enhance the immune effect of subunit vaccines. Therefore, selecting an appropriate adjuvant and immunization method is essential for subunit vaccine research. This review summarizes the past exploration of A. baumannii subunit vaccines, hoping to guide current and future research on these vaccines.

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In SilicoIdentification of Probable Drug and Vaccine Candidates Against Antibiotic-ResistantAcinetobacter baumannii

Cited by 10 publications

References 108 publications

In Silico Analyses of Extracellular Proteins of Acinetobacter baumannii as Immunogenic Candidates

In Silico Analyses of Extracellular Proteins of Acinetobacter baumannii as Immunogenic Candidates

Promising Acinetobacter baumannii Vaccine Candidates and Drug Targets in Recent Years

Subunit vaccines for Acinetobacter baumannii

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