Repair Process Impairment by Pseudomonas aeruginosa in Epithelial Tissues: Major Features and Potential Therapeutic Avenues

Abstract

Epithelial tissues protecting organs from the environment are the first-line of defense against pathogens. Therefore, efficient repair mechanisms after injury are crucial to maintain epithelial integrity. However, these healing processes can be insufficient to restore epithelial integrity, notably in infectious conditions. Pseudomonas aeruginosa infections in cutaneous, corneal, and respiratory tract epithelia are of particular concern because they are the leading causes of hospitalizations, disabilities, and deaths worldwide. Pseudomonas aeruginosa has been shown to alter repair processes, leading to chronic wounds and infections. Because of the current increase in the incidence of multi-drug resistant isolates of P. aeruginosa, complementary approaches to decrease the negative impact of these bacteria on epithelia are urgently needed. Here, we review the recent advances in the understanding of the impact of P. aeruginosa infections on the integrity and repair mechanisms of alveolar, airway, cutaneous and corneal epithelia. Potential therapeutic avenues aimed at counteracting this deleterious impact of infection are also discussed.

Keywords: Pseudomonas aeruginosa infections; airway; burn; cornea; epithelial repair; lung; skin; wound repair.

Figure 1

(A) Structural organization of the human cutaneous, corneal, airway, and alveolar epithelia in healthy conditions. (B) Schematic model of the effects of P. aeruginosa on epithelial integrity. Structural constituents (pili, LPS, lectins) and secreted factors (e.g., pyocyanin, ExoA, LasB, rhamnolipids) contributes to cell death, cytoskeleton disorganization and/or tight junction disruption. Paracellular permeability then favors bacterial transmigration and infiltration toward the basolateral compartment; ECM disruption by MMP and cell detachment to the ECM then favor bacterial propagation. T3SS toxins (e.g., ExoS, ExoT, ExoU, ExoY) injected through the basolateral membrane contribute to cell death and altered epithelial integrity. Pili and flagellum are also involved in bacterial adherence to the host cell. Cytokines, released by epithelial cells, macrophages and infiltrated neutrophils also contribute to epithelial damage. BM, basement membrane; ASL, airway surface liquid; ECM, extracellular matrix.

Figure 2

(A) Schematic model of the negative effects of P. aeruginosa structural constituents (LPS, LecB) and exoproducts (pyocyanin, ExoA, LasB, LasA, T3SS exotoxins) on epithelial cell proliferation, migration and wound repair. As reported in section Evidence for Epithelial Repair Impairment by Pseudomonas aeruginosa, it has to be noted that some factors (LPS, flagellum, 3-oxo-C₁₂-HSL) can also elicit stimulatory effects. (B) Summary of the deleterious effects of P. aeruginosa on epithelial integrity and repair.