Abstract
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.
Highlights
Pseudomonas aeruginosa is a motile and aerobic Gram-negative bacillus, with great diversity and adaptability in a wide range of environments, including non-clinical and clinical settings [1]
This review describes the host immune response against P. aeruginosa; the factors that allow the adaptation of the pathogen to the host; and the numerous vaccine candidates and adjuvants that have been evaluated over half a century of Pseudomonas vaccine development
IL-1β is elevated in the sputum and bronchoalveolar lavage inflammatory response, which is critical for the recruitment of neutrophils and macrophages, fluid of cystic fibrosis (CF) patients colonised with P. aeruginosa, and antibiotic treatment in children was correlated facilitating the bacterial clearance (Figure 2)
Summary
Pseudomonas aeruginosa is a motile and aerobic Gram-negative bacillus, with great diversity and adaptability in a wide range of environments, including non-clinical (soil, aquatic environments or plants) and clinical settings (nosocomial infections and medical equipment, such as inhalers, respirators, and vaporisers) [1]. Sinonasal disease and the occurrence of P. aeruginosa pulmonary colonisation in 210 CF patients, a multitude of genomic and phenotypic adaptations that promote bacterial survival by attenuating suggesting that T2R38, which encodes a taste receptor, is a novel modifier gene in CF [46] These and virulence and avoiding immune recognition have been reported [2,38]. (i) emergence of hypermutators, (ii) appearance of morphology variants, such as small colony variant (SCV) and rugose small colony variant (RSCV), (iii) auxotrophy, (iv) overproduction of alginate and loss of flagellum and pili, leading to a sessile-biofilm lifestyle, (v) changes in the LPS (loss of O-antigen and structural modifications of lipid A), (vi) selection against T3SS and loss of cytotoxicity, (vii) reduction in communication systems (QS), (viii) change in iron uptake strategy from siderophores towards haemoglobin utilisation, (ix) acquisition of antibiotic resistance and (x) loss of virulence [2,39,40,41,42]. These and other modifier genes contribute to the diversity of CF disease, contributing to P. aeruginosa pathogenesis and the adaptation of the bacterium to the host environment
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