Role of Host and Bacterial Lipids in Pseudomonas aeruginosa Respiratory Infections

Abstract

The opportunistic pathogen Pseudomonas aeruginosa is one of the most common agents of respiratory infections and has been associated with high morbidity and mortality rates. The ability of P. aeruginosa to cause severe respiratory infections results from the coordinated action of a variety of virulence factors that promote bacterial persistence in the lungs. Several of these P. aeruginosa virulence mechanisms are mediated by bacterial lipids, mainly lipopolysaccharide, rhamnolipid, and outer membrane vesicles. Other mechanisms arise from the activity of P. aeruginosa enzymes, particularly ExoU, phospholipase C, and lipoxygenase A, which modulate host lipid signaling pathways. Moreover, host phospholipases, such as cPLA₂α and sPLA₂, are also activated during the infectious process and play important roles in P. aeruginosa pathogenesis. These mechanisms affect key points of the P. aeruginosa-host interaction, such as: i) biofilm formation that contributes to bacterial colonization and survival, ii) invasion of tissue barriers that allows bacterial dissemination, iii) modulation of inflammatory responses, and iv) escape from host defenses. In this mini-review, we present the lipid-based mechanism that interferes with the establishment of P. aeruginosa in the lungs and discuss how bacterial and host lipids can impact the outcome of P. aeruginosa respiratory infections.

Keywords: Pseudomonas aeruginosa; inflammation; lipid; phospholipase; respiratory infection; virulence.

Figure 1

Role of host PLA₂ in inflammation and antibacterial defense during P. aeruginosa infection. P. aeruginosa interacts with host cells through the binding of PAMPs of this bacterium, mainly LPS and flagellin to the host receptors TLR4 and TLR5, respectively, leading to NF-kB activation. In parallel, toxins, including ExoS, are also injected by this bacterium into host cells, leading to activation of the transcription factor KLF-2. Both processes result ultimately in the induction and secretion of sPLA₂-IIA. Once in the extracellular media, this enzyme binds bacterial membranes and hydrolyzes their phospholipids leading to bacterial death (140). On the other hand, PAMPs stimulate cPLA₂ translocation and activation via a MAPK-dependent mechanism. This leads to the hydrolysis of phospholipids of host cell membranes and subsequent release of free fatty acids, such as arachidonic acid (AA), and lysophospholipids, such as lysophosphatidyl-choline (Lyso-PC). AA is converted into pro-inflammatory eicosanoids and lyso-PC exert toxic effects on host cells (141, 142).

Figure 2

Scheme model of Pseudomonas aeruginosa virulence factors using a lipid-based mechanisms to cause respiratory infections. Bacterial lipids (green) and bacterial enzymes (yellow) targeting host lipids promote (→) or inhibit (˧) different biological functions during respiratory infections. They can (1) facilitate the biofilm formation of P. aeruginosa, (2) promote the death of host cells and the invasion of tissues, leading to the spread of P. aeruginosa in the bloodstream, (3) interfere with the inflammatory response, and (3) block the host defense (e.g. neutrophils, macrophages). As a result, P. aeruginosa can benefit from lipid mechanisms to persist in its host. Created in BioRender.com.