Intranasal Immunization Strategy To Impede Pilin-Mediated Binding of<i>Pseudomonas aeruginosa</i>to Airway Epithelial Cells

Hsieh, Jennifer C.; Tham, Doris M.; Feng, Weijun; Fan, Huang; Embaie, Selamawit; Liu, Keyi; Dean, Deborah; Hertle, Ralf; FitzGerald, David J.; Mrsny, Randall J.

doi:10.1128/iai.73.11.7705-7717.2005

Cited by 8 publications

(10 citation statements)

References 72 publications

(69 reference statements)

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“…Nevertheless, antigenicity of this region can be improved by conjugation to carriers. Two chimeric proteins were constructed through insertion of different sizes of the DSL region of PAK strain in a non-toxic form of the ETA [138,139]. When administered subcutaneously into rabbits, it produced antibodies against both antigens, which reduced bacterial adherence and neutralised the cell-killing activity of ETA [138].…”

Section: Type 4 Pilimentioning

confidence: 99%

Understanding Pseudomonas aeruginosa–Host Interactions: The Ongoing Quest for an Efficacious Vaccine

Sainz-Mejías

Jurado‐Martín

McClean

2020

Cells

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Pseudomonas aeruginosa is a leading cause of chronic respiratory infections in people with cystic fibrosis (CF), bronchiectasis or chronic obstructive pulmonary disease (COPD), and acute infections in immunocompromised individuals. The adaptability of this opportunistic pathogen has hampered the development of antimicrobial therapies, and consequently, it remains a major threat to public health. Due to its antimicrobial resistance, vaccines represent an alternative strategy to tackle the pathogen, yet despite over 50 years of research on anti-Pseudomonas vaccines, no vaccine has been licensed. Nevertheless, there have been many advances in this field, including a better understanding of the host immune response and the biology of P. aeruginosa. Multiple antigens and adjuvants have been investigated with varying results. Although the most effective protective response remains to be established, it is clear that a polarised Th2 response is sub-optimal, and a mixed Th1/Th2 or Th1/Th17 response appears beneficial. This comprehensive review collates the current understanding of the complexities of P. aeruginosa-host interactions and its implication in vaccine design, with a view to understanding the current state of Pseudomonal vaccine development and the direction of future efforts. It highlights the importance of the incorporation of appropriate adjuvants to the protective antigen to yield optimal protection.

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Section: Type 4 Pilimentioning

confidence: 99%

Understanding Pseudomonas aeruginosa–Host Interactions: The Ongoing Quest for an Efficacious Vaccine

Sainz-Mejías

Jurado‐Martín

McClean

2020

Cells

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“…Furthermore, immunological studies indicated that the specific humoral immune response against DSL region can be protective in animal models (Cachia and Hodges ; Hsieh et al . ). The existence of this protective epitope, two β ‐turns conformational region and unique curved shape helps DSL zone to induce production of cross‐reactive antibodies against this region (Sheth et al .…”

Section: Introductionmentioning

confidence: 97%

Immunogenicity of a fusion protein containing PilQ and disulphide turn region of PilA fromPseudomonas aeruginosain mice

Gholami

Chirani

Razavi

et al. 2017

Lett Appl Microbiol

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In this study we examined the potential of integrated PilQ/PilA (QA) antigen as a vaccine candidate against Pseudomonas aeruginosa. Nowadays, anti-adhesion based vaccines are considered as new means to prevent or treat bacterial infections. Our study revealed that chimeric protein PilQ and disulphide turn region of PilA triggers production of specific antibodies. This humoral immune responses augmented when QA was administered in combination with an adjuvant. The results demonstrated efficacy of the designed recombinant chimeric antigen as an effective candidate in prevention of P. aeruginosa infection.

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“…It is of interest to determine all of the regions exposed to the environment under tension for understanding the extraordinary plasticity of GC-T4P filaments. In addition, by uncovering what regions of the pilus filament become exposed under strain, more effective drugs, acting as inhibitors to T4P binding, could potentially be engineered [13], [14].…”

Section: Introductionmentioning

confidence: 99%

Steered Molecular Dynamics Simulations of a Type IV Pilus Probe Initial Stages of a Force-Induced Conformational Transition

2013

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Type IV pili are long, protein filaments built from a repeating subunit that protrudes from the surface of a wide variety of infectious bacteria. They are implicated in a vast array of functions, ranging from bacterial motility to microcolony formation to infection. One of the most well-studied type IV filaments is the gonococcal type IV pilus (GC-T4P) from Neisseria gonorrhoeae, the causative agent of gonorrhea. Cryo-electron microscopy has been used to construct a model of this filament, offering insights into the structure of type IV pili. In addition, experiments have demonstrated that GC-T4P can withstand very large tension forces, and transition to a force-induced conformation. However, the details of force-generation, and the atomic-level characteristics of the force-induced conformation, are unknown. Here, steered molecular dynamics (SMD) simulation was used to exert a force in silico on an 18 subunit segment of GC-T4P to address questions regarding the nature of the interactions that lead to the extraordinary strength of bacterial pili. SMD simulations revealed that the buried pilin α1 domains maintain hydrophobic contacts with one another within the core of the filament, leading to GC-T4P's structural stability. At the filament surface, gaps between pilin globular head domains in both the native and pulled states provide water accessible routes between the external environment and the interior of the filament, allowing water to access the pilin α1 domains as reported for VC-T4P in deuterium exchange experiments. Results were also compared to the experimentally observed force-induced conformation. In particular, an exposed amino acid sequence in the experimentally stretched filament was also found to become exposed during the SMD simulations, suggesting that initial stages of the force induced transition are well captured. Furthermore, a second sequence was shown to be initially hidden in the native filament and became exposed upon stretching.

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Intranasal Immunization Strategy To Impede Pilin-Mediated Binding ofPseudomonas aeruginosato Airway Epithelial Cells

Cited by 8 publications

References 72 publications

Understanding Pseudomonas aeruginosa–Host Interactions: The Ongoing Quest for an Efficacious Vaccine

Understanding Pseudomonas aeruginosa–Host Interactions: The Ongoing Quest for an Efficacious Vaccine

Immunogenicity of a fusion protein containing PilQ and disulphide turn region of PilA fromPseudomonas aeruginosain mice

Steered Molecular Dynamics Simulations of a Type IV Pilus Probe Initial Stages of a Force-Induced Conformational Transition

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