scholarly journals Development of Novel Protective Polyvalent Irradiated Pseudomonas aeruginosa Vaccine for Immuno-Compromised Patients

2021 ◽  
Vol 16 ◽  
pp. 1-10
Author(s):  
Manal M.E. Ahmed ◽  
Jakeen Eljakee ◽  
Tarek Mahran
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Protective Efficacy ◽  
Challenge Test ◽  
Opportunistic Pathogen ◽  
Effective Vaccine ◽  
The Novel ◽  
Therapeutic Approaches ◽  
Promising Strategy ◽  
Antigenic Expression ◽  
Compromised Patients

Pseudomonas aeruginosa is an opportunistic pathogen affecting immuno-compromised patients; however, no effective vaccine is currently available in the market. Here, we developed novel polyvalent irradiated P. aeruginosa vaccine using cobalt 60 that inhibited pathogen viability but retained antigenic expression functionally. Mice were vaccinated by the developed vaccine by intranasal, intramuscular and subcutaneous route of administration followed by challenge test. The protective efficacy of the novel vaccine reached up to 95%. This significant protection was mainly associated with measurable antiserum opsonic killing activity. In conclusion, the novel vaccine provides a promising strategy of both prophylactic and therapeutic approaches for immuno-compromised patients against MDR P. aeruginosa.

scholarly journals Effect of Two Unique Nanoparticle Formulations on the Efficacy of a Broadly Protective Vaccine Against Pseudomonas Aeruginosa

2021 ◽  
Vol 12 ◽  
Author(s):  
Debaki R. Howlader ◽  
Sayan Das ◽  
Ti Lu ◽  
Gang Hu ◽  
David J. Varisco ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Lipid A ◽  
Protective Efficacy ◽  
Initial Step ◽  
Opportunistic Pathogen ◽  
Multi Drug Resistance ◽  
Successful Vaccine ◽  
Wide Range ◽  
Tlr4 Agonist ◽  
Opsonophagocytic Killing

Pseudomonas aeruginosa is an opportunistic pathogen responsible for a wide range of infections in humans. In addition to its innate antibiotic resistance, P. aeruginosa is very effective in acquiring resistance resulting in the emergence of multi-drug resistance strains and a licensed vaccine is not yet available. We have previously demonstrated the protective efficacy of a novel antigen PaF (Pa Fusion), a fusion of the type III secretion system (T3SS) needle tip protein, PcrV, and the first of two translocator proteins, PopB. PaF was modified to provide a self-adjuvanting activity by fusing the A1 subunit of the heat-labile enterotoxin from Enterotoxigenic E. coli to its N-terminus to give L-PaF. In addition to providing protection against 04 and 06 serotypes of P. aeruginosa, L-PaF elicited opsonophagocytic killing and stimulated IL-17A secretion, which have been predicted to be required for a successful vaccine. While monomeric recombinant subunit vaccines can be protective in mice, this protection often does not transfer to humans where multimeric formulations perform better. Here, we use two unique formulations, an oil-in-water (o/w) emulsion and a chitosan particle, as well as the addition of a unique TLR4 agonist, BECC438 (a detoxified lipid A analogue designated Bacterial Enzymatic Combinatorial Chemistry 438), as an initial step in optimizing L-PaF for use in humans. The o/w emulsion together with BECC438 provided the best protective efficacy, which correlated with high levels of opsonophagocytic killing and IL-17A secretion, thereby reducing the lung burden among all the vaccinated groups tested.

A novel design of multi-epitope peptide vaccine against Pseudomonas aeruginosa

2021 ◽  
Vol 18 ◽  
Author(s):  
Fatemeh Esmaeilzadeh ◽  
Shirin Mahmoodi
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Outer Membrane Proteins ◽  
Peptide Vaccine ◽  
Opportunistic Pathogen ◽  
Bacterial Attachment ◽  
Effective Vaccine ◽  
Epitope Peptide ◽  
Neisseria Meningitides ◽  
Type Iv ◽  
Cell Immunity

Background: As an opportunistic pathogen, Pseudomonas aeruginosa causes many different hazardous infections. The high mortality rate resulting from infection with this antibiotic-resistant pathogen has made it a major challenge in clinical treatment; it has been listed as the most harmful bacterium to humans by the WHO. So far, no vaccine has been approved for P. aeruginosa. Objective: Infections performed by bacterial attachment and colonization with type IV pili (T4P), known as the most essential adhesive vital for adhesion, while pilQ is necessary for the biogenesis of T4P, also outer membrane proteins of a pathogen is also effective in stimulating the immune system; in this regard, pilQ, OprF, and OprI, are excellent candidate antigens for production of an effective vaccine against P. aeruginosa. Methods: In this research, various bioinformatics methods were employed in order to design a new multi-epitope peptide vaccine versus P. aeruginosa. Since T CD4+ cell immunity is important in eradicating P. aeruginosa, OprF, OprI, and pilQ antigens were analyzed to determineHelper T cell Lymphocyte (HTL) epitopes by many different immunoinformatics servers. One of the receptor agonists 2 (TLR2), a segment of the Por B protein from Neisseria meningitides was used as an adjuvant in order to stimulate an effective cellular immune response, and suitable linkers were used to connect all the above mentioned parts. In the vaccine construct, linear B cell epitopes were also identified. Results: Conforming the bioinformatics forecasts, the designed vaccine possesses high antigenicity and is not allergen. Conclusion: In this regard, the designed vaccine candidate is strongly believed to possess the potential of inducing cellular and humoral immunity against P. aeruginosa.

scholarly journals Anti-Virulence Properties of Coridothymus capitatus Essential Oil against Pseudomonas aeruginosa Clinical Isolates from Cystic Fibrosis Patients

2021 ◽  
Vol 9 (11) ◽  
pp. 2257
Author(s):  
Gianluca Vrenna ◽  
Marco Artini ◽  
Rino Ragno ◽  
Michela Relucenti ◽  
Ersilia Vita Fiscarelli ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Opportunistic Pathogen ◽  
Sem Analysis ◽  
Adhesion Assay ◽  
Potential Candidate ◽  
The Novel ◽  
Airway Infections ◽  
Almost All ◽  
Specific Virulence

Pseudomonas aeruginosa is an opportunistic pathogen responsible for nosocomial infections, and is often involved in airway infections of cystic fibrosis (CF) patients. P. aeruginosa virulence is related to its ability to form biofilm, trigger different types of motilities, and produce toxins (for example, bacterial pigments). In this scenario, essential oils (EOs) have gained notoriety for their role in phenotype modulation, including virulence modulation. Among different EOs previously analyzed, herein we investigated the activity of Coridothymus capitatus EO (CCEO) against specific virulence factors produced by P. aeruginosa isolated from CF patients. CCEO showed inhibition of new biofilm formation and reduction in mature biofilm in about half of the tested strains. On selected strains, SEM analysis provided interesting information regarding CCEO action in a pre-adhesion assay. CCEO treatment showed a dramatic modification of the extracellular matrix (ECM) structure. Our results clearly showed a drastic reduction in pyocyanin production (between 84% and 100%) for all tested strains in the presence of CCEO. Finally, CCEO was also able to strongly affect P. aeruginosa swarming and swimming motility for almost all tested strains. In consideration of the novel results obtained on clinical strains isolated from CF patients, CCEO may be a potential candidate to limit P. aeruginosa virulence.

The In Vitro Antibiofilm Activity of Water Leaf Extract of Papaya (Carica papaya L.) against Pseudomonas aeruginosa

2017 ◽  
Vol 2 (3) ◽  
pp. 150-163
Author(s):  
Ekajayanti Kining ◽  
Syamsul Falah ◽  
Novik Nurhidayat
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Contact Time ◽  
Cell Attachment ◽  
Water Extract ◽  
Opportunistic Pathogen ◽  
Bacterial Biofilm ◽  
Antibiofilm Activity ◽  
Bacterial Survival ◽  
Optimum Conditions

Pseudomonas aeruginosa is one of opportunistic pathogen forming bacterial biofilm. The biofilm sustains the bacterial survival and infections. This study aimed to assess the activity of water extract of papaya leaves on inhibition of cells attachment, growth and degradation of the biofilm using crystal violet (CV) biofilm assay. Research results showed that water extract of papaya leaves contains alkaloids, tanins, flavonoids, and steroids/terpenoids and showed antibacterial activity and antibiofilm against P. aeruginosa. Addition of extract can inhibit the cell attachment and was able to degrade the biofilm of 40.92% and 48.058% respectively at optimum conditions: extract concentration of 25% (v/v), temperature 37.5 °C and contact time 45 minutes. With a concentration of 25% (v/v), temperature of 50 °C and the contact time of 3 days, extract of papaya leaves can inhibit the growth of biofilms of 39.837% v/v.

scholarly journals Prevalence of metallo-β-lactamase genes among Pseudomonas aeruginosa isolated from various clinical samples in China

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Wei Wang ◽  
Xiaoya Wang
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Susceptibility ◽  
Ethylenediaminetetraacetic Acid ◽  
Carbapenem Resistance ◽  
Opportunistic Pathogen ◽  
Detection Methods ◽  
Clinical Samples ◽  
Routine Practice ◽  
Carbapenem Resistant ◽  
High Prevalence

AbstractBackgroundPseudomonas aeruginosa is an opportunistic pathogen which is associated with nosocomial infections and causes various diseases including urinary tract infection, pneumonia, soft-tissue infection and sepsis. The emergence of P. aeruginosa-acquired metallo-β-lactamase (MBL) is most worrisome and poses a serious threat during treatment and infection control. The objective of this study was to identify antibiotic susceptibility, phenotypic detection of MBL production and to determine the prevalence of MBL genes in carbapenem-resistant P. aeruginosa isolated from different clinical samples.MethodsA total of 329 non-duplicate P. aeruginosa isolated from various clinical samples from two hospitals in China between September 2017 and March 2019 were included in this study. Phenotypic detection of MBL was performed by the combined detection method using imipenem and imipenem-ethylenediaminetetraacetic acid (EDTA) discs. MBL-encoding genes including blaVIM-1, blaVIM-2, blaIMP-1, blaIMP-2, blaSPM-1, blaSIM, blaNDM-1 and blaGIM were detected by polymerase chain reaction (PCR).ResultsOf the 329 P. aeruginosa, majority of the isolates were resistant to imipenem (77.5%) followed by meropenem (64.7%). Of the 270 P. aeruginosa isolates tested, 149 (55.2%) isolates were found to be positive for MBL detection. Of the different samples, 57.8% (n = 26) of P. aeruginosa isolated from blood were found to be positive for MBL production. Of the various MBL genes, blaIMP-1 (28.2%) was the most predominant gene detected followed by blaVIM-2 (18.8%), blaVIM-1 (16.1%), blaNDM-1 (9.4%), blaIMP-2 (6.7%), blaSIM (6.0%), blaSPM-1 (4.0%) and blaGIM (1.3%) genes.ConclusionsThe high resistance of P. aeruginosa toward imipenem and meropenem and the high prevalence of blaIMP-1 and blaVIM-2 set the alarm on the increasing, perhaps the increased, carbapenem resistance. In addition to routine antibiotic susceptibility testings, our results emphasize the importance of both the phenotypic and genotypic MBL detection methods in routine practice for early detection of carbapenem resistance and to prevent further dissemination of this resistant pathogen.

scholarly journals Strategies for Vaccination: Conventional Vaccine Approaches Versus New-Generation Strategies in Combination with Adjuvants

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 140
Author(s):  
Abdellatif Bouazzaoui ◽  
Ahmed A. H. Abdellatif ◽  
Faisal A. Al-Allaf ◽  
Neda M. Bogari ◽  
Saied Al-Dehlawi ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Protein Production ◽  
Vaccine Development ◽  
Effective Vaccine ◽  
The Novel ◽  
Research Teams ◽  
Advantages And Disadvantages ◽  
Rapid Spread ◽  
New Generation ◽  
Conventional Vaccine

The current COVID-19 pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has raised significant economic, social, and psychological concerns. The rapid spread of the virus, coupled with the absence of vaccines and antiviral treatments for SARS-CoV-2, has galvanized a major global endeavor to develop effective vaccines. Within a matter of just a few months of the initial outbreak, research teams worldwide, adopting a range of different strategies, embarked on a quest to develop effective vaccine that could be effectively used to suppress this virulent pathogen. In this review, we describe conventional approaches to vaccine development, including strategies employing proteins, peptides, and attenuated or inactivated pathogens in combination with adjuvants (including genetic adjuvants). We also present details of the novel strategies that were adopted by different research groups to successfully transfer recombinantly expressed antigens while using viral vectors (adenoviral and retroviral) and non-viral delivery systems, and how recently developed methods have been applied in order to produce vaccines that are based on mRNA, self-amplifying RNA (saRNA), and trans-amplifying RNA (taRNA). Moreover, we discuss the methods that are being used to enhance mRNA stability and protein production, the advantages and disadvantages of different methods, and the challenges that are encountered during the development of effective vaccines.

scholarly journals Mutational hotspots and conserved domains of SARS-CoV-2 genome in African population

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Olabode E. Omotoso ◽  
Ayoade D. Babalola ◽  
Amira Matareek
Keyword(s):  
Global Economy ◽  
African Population ◽  
The Novel ◽  
Conserved Domains ◽  
Nucleocapsid Proteins ◽  
Genome Variability ◽  
Promising Strategy ◽  
Mutational Hotspots ◽  
Novel Coronavirus ◽  
Complete Protein

Abstract Background Since outbreak in December 2019, the highly infectious and pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over a million deaths globally. With increasing burden, the novel coronavirus has posed a dire threat to public health, social interaction, and global economy. Mutations in the SARS-CoV-2 genome are moderately evolving which might have contributed to its genome variability, transmission, replication efficiency, and virulence in different regions of the world. Results The present study elucidated the mutational landscape in the SARS-CoV-2 genome among the African populace, which may have contributed to the virulence, spread, and pathogenicity observed in the region. A total of 3045 SARS-CoV-2 complete protein sequences with the reference viral sequence (EPI_ISL_402124) were mined and analyzed. SARS-CoV-2 ORF1ab, spike, ORF3, ORF8, and nucleocapsid proteins were observed as mutational hotspots in the African population and may be of keen interest in understanding the viral host relationship, while there is conservation in the ORF6, ORF7a, ORF7b, ORF10, envelope, and membrane proteins. Conclusions The accumulation of moderate mutations (though slowly), in the SARS-CoV-2 genome as seen in this present study, could be a promising strategy to develop antiviral drugs or vaccines. These antiviral interventions should target viral conserved domains and host cellular proteins and/or receptors involved in viral invasion and replication to avoid a new viral wave due to drug resistance and vaccine evasion.

scholarly journals Genome-Scale Metabolic Network Analysis of the Opportunistic Pathogen Pseudomonas aeruginosa PAO1

2008 ◽  
Vol 190 (8) ◽  
pp. 2790-2803 ◽  
Author(s):  
Matthew A. Oberhardt ◽  
Jacek Puchałka ◽  
Kimberly E. Fryer ◽  
Vítor A. P. Martins dos Santos ◽  
Jason A. Papin
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Metabolic Network ◽  
Opportunistic Pathogen ◽  
Scale Model ◽  
Modeling Framework ◽  
Major Life ◽  
Metabolic Versatility ◽  
A Genome ◽  
Scale Properties ◽  
Genome Scale

ABSTRACT Pseudomonas aeruginosa is a major life-threatening opportunistic pathogen that commonly infects immunocompromised patients. This bacterium owes its success as a pathogen largely to its metabolic versatility and flexibility. A thorough understanding of P. aeruginosa's metabolism is thus pivotal for the design of effective intervention strategies. Here we aim to provide, through systems analysis, a basis for the characterization of the genome-scale properties of this pathogen's versatile metabolic network. To this end, we reconstructed a genome-scale metabolic network of Pseudomonas aeruginosa PAO1. This reconstruction accounts for 1,056 genes (19% of the genome), 1,030 proteins, and 883 reactions. Flux balance analysis was used to identify key features of P. aeruginosa metabolism, such as growth yield, under defined conditions and with defined knowledge gaps within the network. BIOLOG substrate oxidation data were used in model expansion, and a genome-scale transposon knockout set was compared against in silico knockout predictions to validate the model. Ultimately, this genome-scale model provides a basic modeling framework with which to explore the metabolism of P. aeruginosa in the context of its environmental and genetic constraints, thereby contributing to a more thorough understanding of the genotype-phenotype relationships in this resourceful and dangerous pathogen.

scholarly journals Disease Mechanisms and Therapeutic Approaches in C9orf72 ALS-FTD

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 601
Author(s):  
Keith Mayl ◽  
Christopher E. Shaw ◽  
Youn-Bok Lee
Keyword(s):  
The Body ◽  
The Novel ◽  
Therapeutic Approaches ◽  
Gain Of Function ◽  
Pathogenic Mechanisms ◽  
Hexanucleotide Repeat ◽  
Primary Driver ◽  
Hexanucleotide Repeat Expansion ◽  
Expansion Mutation ◽  
Lateral Sclerosis

A hexanucleotide repeat expansion mutation in the first intron of C9orf72 is the most common known genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Since the discovery in 2011, numerous pathogenic mechanisms, including both loss and gain of function, have been proposed. The body of work overall suggests that toxic gain of function arising from bidirectionally transcribed repeat RNA is likely to be the primary driver of disease. In this review, we outline the key pathogenic mechanisms that have been proposed to date and discuss some of the novel therapeutic approaches currently in development.

scholarly journals Presence of Chromosomal crpP-like Genes Is Not Always Associated with Ciprofloxacin Resistance in Pseudomonas aeruginosa Clinical Isolates Recovered in ICU Patients from Portugal and Spain

2021 ◽  
Vol 9 (2) ◽  
pp. 388
Author(s):  
Marta Hernández-García ◽  
María García-Castillo ◽  
Sergio García-Fernández ◽  
Diego López-Mendoza ◽  
Jazmín Díaz-Regañón ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Protein Function ◽  
Resistance Mechanism ◽  
Amino Acid Position ◽  
Genomic Islands ◽  
Missense Mutations ◽  
The Novel ◽  
Surveillance Studies ◽  
Ciprofloxacin Resistance ◽  
Chromosomal Mutations

CrpP enzymes have been recently described as a novel ciprofloxacin-resistance mechanism. We investigated by whole genome sequencing the presence of crpP-genes and other mechanisms involved in quinolone resistance in MDR/XDR-Pseudomonas aeruginosa isolates (n = 55) with both ceftolozane-tazobactam susceptible or resistant profiles recovered from intensive care unit patients during the STEP (Portugal) and SUPERIOR (Spain) surveillance studies. Ciprofloxacin resistance was associated with mutations in the gyrA and parC genes. Additionally, plasmid-mediated genes (qnrS2 and aac(6′)-Ib-cr) were eventually detected. Ten chromosomal crpP-like genes contained in related pathogenicity genomic islands and 6 different CrpP (CrpP1-CrpP6) proteins were found in 65% (36/55) of the isolates. Dissemination of CrpP variants was observed among non-related clones of both countries, including the CC175 (Spain) high-risk clone and CC348 (Portugal) clone. Interestingly, 5 of 6 variants (CrpP1-CrpP5) carried missense mutations in an amino acid position (Gly7) previously defined as essential conferring ciprofloxacin resistance, and decreased ciprofloxacin susceptibility was only associated with the novel CrpP6 protein. In our collection, ciprofloxacin resistance was mainly due to chromosomal mutations in the gyrA and parC genes. However, crpP genes carrying mutations essential for protein function (G7, I26) and associated with a restored ciprofloxacin susceptibility were predominant. Despite the presence of crpP genes is not always associated with ciprofloxacin resistance, the risk of emergence of novel CrpP variants with a higher ability to affect quinolones is increasing. Furthermore, the spread of crpP genes in highly mobilizable genomic islands among related and non-related P. aeruginosa clones alert the dispersion of MDR pathogens in hospital settings.

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