Modifications of Pseudomonas aeruginosa cell envelope in the cystic fibrosis airway alters interactions with immune cells

Abstract

Pseudomonas aeruginosa is a ubiquitous environmental organism and an opportunistic pathogen that causes chronic lung infections in the airways of cystic fibrosis (CF) patients as well as other immune-compromised individuals. During infection, P. aeruginosa enters the terminal bronchioles and alveoli and comes into contact with alveolar lining fluid (ALF), which contains homeostatic and antimicrobial hydrolytic activities, termed hydrolases. These hydrolases comprise an array of lipases, glycosidases, and proteases and thus, they have the potential to modify lipids, carbohydrates and proteins on the surface of invading microbes. Here we show that hydrolase levels between human ALF from healthy and CF patients differ. CF-ALF influences the P. aeruginosa cell wall by reducing the content of one of its major polysaccharides, Psl. This CF-ALF induced Psl reduction does not alter initial bacterial attachment to surfaces but reduces biofilm formation. Importantly, exposure of P. aeruginosa to CF-ALF drives the activation of neutrophils and triggers their oxidative response; thus, defining human CF-ALF as a new innate defense mechanism to control P. aeruginosa infection, but at the same time potentially adding to the chronic inflammatory state of the lung in CF patients.

Tasked with a Challenging Objective: Why Do Neutrophils Fail to Battle Pseudomonas aeruginosa Biofilms

“…Another recent study demonstrated that α-mannosidase reduced in vitro biofilms [68]. We confirmed and expanded on these findings by providing evidence that neutrophil-derived α-mannosidases (Man2b1 and Man2c1) activity was needed for optimal bactericidal function against P. aeruginosa [28].…”

Frontline Science: Employing enzymatic treatment options for management of ocular biofilm-based infections

“…Consistent with recently published data by others, we observed that treatment with α‐mannosidase in vitro decreased P. aeruginosa biofilms. Another recent study demonstrated that α‐mannosidase targeted Psl . Furthermore, Psl inhibited neutrophil bactericidal activity and protected bacteria from proteolytic attach by neutrophil elastase .…”

“…Because Psl is a polymer of pentameric repeating Another recent study demonstrated that -mannosidase targeted Psl. 37 Furthermore, Psl inhibited neutrophil bactericidal activity 37 and protected bacteria from proteolytic attach by neutrophil elastase. 25 We confirmed and expanded on this foundation by providing evidence that neutrophil-derived -mannosidase activity is needed for optimal bactericidal function against P. aeruginosa and that the topical application of -mannosidase decreased corneal bacterial burden in vivo at least initially during infection (Fig.…”

“…Given that Psl is a mannose-rich polysaccharide and thatmannosidase digests, 37 the biofilm-reducing capacity of exogenously added -mannosidase was examined. Bacterial biofilms of P. aeruginosa 6294 were grown for 24 h and treated with -mannosidase for 3 h at 37 • C after biofilms had formed.…”

Variation of Burkholderia cenocepacia cell wall morphology and mechanical properties during cystic fibrosis lung infection, assessed by atomic force microscopy

“…Under those stresses, several genetic changes accumulate in the initial infecting bacterial strain leading to phenotype and genotype heterogeneity. CF bacterial pathogens phenotypic diversification can be recognized in terms of colony morphology diversity 11–17 and variation of clinically relevant phenotypes such as antibiotic resistance 11,17–20 , ability to form biofilms 16,21–24 , virulence potential 14,25–27 , among many others 12,17,28–32 . Remarkably, such phenotypic heterogeneity within human hosts has important clinical implications.…”