A targeted boost-and-sort immunization strategy using Escherichia coli BamA identifies rare growth inhibitory antibodies

Vij, Rajesh; Lin, Zhonghua; Chiang, Nancy Y.; Vernes, Jean-Michel; Storek, Kelly M.; Park, Summer; Chan, Joyce; Meng, Yaqi; Comps-Agrar, Laëtitia; Luan, Peng; Lee, Sophia; Schneider, Kellen; Bevers, Jack; Zilberleyb, Inna; Tam, Christine; Koth, Christopher M.; Xu, Min; Gill, Avinash; Auerbach, Marcy R.; Smith, Peter A.; Rutherford, Steven T.; Nakamura, Gerald; Seshasayee, Dhaya; Payandeh, Jian; Koerber, James T.

doi:10.1038/s41598-018-25609-z

Cited by 31 publications

(23 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…OMPs include a functional role in bacterial pathogenesis, OM permeability barrier, efflux pumps, diffusions of nutrients, membrane integrity and in active transport. For chimeric vaccine construction, bacterial OMPs has selected because of their antigenic and immunogenic behavior 34 . OMPs that plays an essential and virulent factor role may be useful in therapeutics design.…”

Section: Methodsmentioning

confidence: 99%

Prioritization of potential vaccine targets using comparative proteomics and designing of the chimeric multi-epitope vaccine against Pseudomonas aeruginosa

Solanki

Tiwari

2019

Sci Rep

View full text Add to dashboard Cite

Multidrug-resistant Pseudomonas aeruginosa is one of the worldwide health problems involved in elevated mortality and morbidity. Therefore, it is important to find a therapeutic for this pathogen. In the present study, we have designed a chimeric vaccine against P. aeruginosa with the help of comparative proteomics and reverse vaccinology approaches. Using comparative subtractive proteomic analysis of 1,191 proteomes of P. aeruginosa , a total of twenty unique non-redundant proteomes were selected. In these proteomes, fifteen outer membrane proteins (OMPs) of P. aeruginosa were selected based on the basis of hydrophilicity, non-secretory nature, low transmembrane helix (<1), essentiality, virulence, pathway association, antigenic, and protein-protein network analysis. Reverse vaccinology approach was used to identify antigenic and immunogenic MHC class I, MHC class II and B cell epitopes present in the selected OMPs that can enhance T cell and B cell mediated immunogenicity. The selected epitopes were shortlisted based on their allergenicity, toxicity potentials, solubility, and hydrophilicity analysis. Immunogenic peptides were used to design a multi-epitope vaccine construct. Immune-modulating adjuvants and PADRE (Pan HLA-DR epitopes) sequence were added with epitopes sequence to enhance the immunogenicity. All the epitopes, adjuvants and PADRE sequence were joined by linkers. The designed vaccine constructs (VT1, VT2, VT3, and VT4) were analyzed by their physiochemical properties using different tools. Selected chimeric vaccine constructs (VT1, VT3, and VT4) were further shortlisted by their docking score with different HLA alleles. The final selected VT4 construct was docked with TLR4/MD2 complex and confirmed by molecular dynamics simulation studies. The final vaccine VT-4 construct was in-silico cloned in pET28a. Therefore, the designed construct VT4 may be studied to control the interaction of P. aeruginosa with host and infection caused by P. aeruginosa .

show abstract

Section: Methodsmentioning

confidence: 99%

Prioritization of potential vaccine targets using comparative proteomics and designing of the chimeric multi-epitope vaccine against Pseudomonas aeruginosa

Solanki

Tiwari

2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Thus, it is well recognized that the BAM complex itself as well as chaperones in delivering proteins to the outer membrane are critical for membrane integrity as well as antibiotic resistance and could therefore be targets for drug development (Tamae et al, 2008; Weirich et al, 2017; Storek et al, 2018; Vij et al, 2018). Nevertheless, previous studies revealed species-specific differences in the importance of individual components in OMP biogenesis such as Skp and SurA (Sklar et al, 2007; Volokhina et al, 2011; Weirich et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Deprivation of the Periplasmic Chaperone SurA Reduces Virulence and Restores Antibiotic Susceptibility of Multidrug-Resistant Pseudomonas aeruginosa

Klein¹,

Sonnabend²,

Frank³

et al. 2019

Front. Microbiol.

View full text Add to dashboard Cite

Pseudomonas aeruginosa is one of the main causative agents of nosocomial infections and the spread of multidrug-resistant strains is rising. Therefore, novel strategies for therapy are urgently required. The outer membrane composition of Gram-negative pathogens and especially of Pa restricts the efficacy of antibiotic entry into the cell and determines virulence. For efficient outer membrane protein biogenesis, the β-barrel assembly machinery (BAM) complex in the outer membrane and periplasmic chaperones like Skp and SurA are crucial. Previous studies indicated that the importance of individual proteins involved in outer membrane protein biogenesis may vary between different Gram-negative species. In addition, since multidrug-resistant Pa strains pose a serious global threat, the interference with both virulence and antibiotic resistance by disturbing outer membrane protein biogenesis might be a new strategy to cope with this challenge. Therefore, deletion mutants of the non-essential BAM complex components bamB and bamC , of the skp homolog hlpA as well as a conditional mutant of surA were investigated. The most profound effects for both traits were associated with reduced levels of SurA, characterized by increased membrane permeability, enhanced sensitivity to antibiotic treatment and attenuation of virulence in a Galleria mellonella infection model. Strikingly, the depletion of SurA in a multidrug-resistant clinical bloodstream isolate re-sensitized the strain to antibiotic treatment. From our data we conclude that SurA of Pa serves as a promising target for developing a drug that shows antiinfective activity and re-sensitizes multidrug-resistant strains to antibiotics.

show abstract

“…Several studies aimed to identify the useful substance in these structural components for immunization against bacterial infection; however, almost all studies did not achieve the establishment of an effective strategy in the immunization. In fact, the immunization strategies using bacterial components have several side effects and lack a long-term immunization effect [18,19]. Furthermore, the exact immune response by the immunization is difficult to characterize in individuals [20,21].…”

Section: Discussionmentioning

confidence: 99%

Immunization with a Bacterial Lipoprotein Establishes an Immuno-Protective Response with Upregulation of Effector CD4+ T Cells and Neutrophils Against Methicillin-Resistant Staphylococcus aureus Infection

Zhang

Cao

et al. 2020

Pathogens

View full text Add to dashboard Cite

Staphylococcus aureus (S. aureus) is a commensal bacterium in the human body; however, the bacterium frequently generates serious inflammation and infectious diseases. Some strains of S. aureus, such as methicillin-resistant Staphylococcus aureus (MRSA), are still a serious problem in public health facilities. Thus, an effective protection strategy is eagerly expected for the prevention and cure of MRSA infection. Here, we report that a specific fraction of an S. aureus lipoprotein (SA-LP) established a protective response against MRSA infection. The fractionated S. aureus lipoprotein SA-LP-F2, which is contained in 30–50 kDa of crude S. aureus lipoprotein (SA-LP-C), effectively activated dendritic cells (DCs) and the SA-LP-F2-pulsed DCs generated IFN-γ+CD4+ T (Th1) and IL-17A+CD4+ T (Th17) cells by in vitro antigen presentation. The SA-LP-F2 immunization upregulated the Th1 and Th17 populations so that MRSA colonization on the skin was suppressed during the challenge phase with MRSA. By following the effector T cell upregulation, the neutrophil function, which was a substantial effector cell against MRSA, was also enhanced in the SA-LP-F2-immunized mice. Finally, we found that the protective effect of SA-LP-F2 immunization was maintained for at least 90 days because the immunized mice continued to show a protective response during the MRSA challenge period. In the MRSA challenge, reactivated Th1 and Th17 populations were maintained in the SA-LP-F2-immunized mice as compared to naive mice. In addition, the neutrophil population was also upregulated in the mice. The memory CD4+ T cell (central memory T; TCM and effector memory T; TEM) population was established by SA-LP-F2 immunization and was maintained at higher levels than usual. Taken together, our findings may provide a breakthrough in the establishment of an immunization strategy against MRSA infection.

show abstract

A targeted boost-and-sort immunization strategy using Escherichia coli BamA identifies rare growth inhibitory antibodies

Cited by 31 publications

References 38 publications

Prioritization of potential vaccine targets using comparative proteomics and designing of the chimeric multi-epitope vaccine against Pseudomonas aeruginosa

Prioritization of potential vaccine targets using comparative proteomics and designing of the chimeric multi-epitope vaccine against Pseudomonas aeruginosa

Deprivation of the Periplasmic Chaperone SurA Reduces Virulence and Restores Antibiotic Susceptibility of Multidrug-Resistant Pseudomonas aeruginosa

Immunization with a Bacterial Lipoprotein Establishes an Immuno-Protective Response with Upregulation of Effector CD4+ T Cells and Neutrophils Against Methicillin-Resistant Staphylococcus aureus Infection

Contact Info

Product

Resources

About