Abstract
Pseudomonas aeruginosa efficiently adheres to human tissues, including the lungs and skin, causing infections that are difficult to treat. Laminin is a main component of the extracellular matrix, and in this study we defined bacterial laminin receptors on P. aeruginosa. Persistent clinical P. aeruginosa isolates from patients with cystic fibrosis, wounds or catheter-related urinary tract infections bound more laminin compared to blood isolates. Laminin receptors in the outer membrane were revealed by 2D-immunblotting, and the specificities of interactions were confirmed with ELISA and biolayer interferometry. Four new high-affinity laminin receptors were identified in the outer membrane; EstA, OprD, OprG and PA3923. Mutated bacteria devoid of these receptors adhered poorly to immobilized laminin. All bacterial receptors bound to the heparin-binding domains on LG4 and LG5 of the laminin alpha chain as assessed with truncated laminin fragments, transmission electron microscopy and inhibition by heparin. In conclusion, P. aeruginosa binds laminin via multiple surface receptors, and isolates from lungs of cystic fibrosis patients bound significantly more laminin compared to bacteria isolated from the skin and urine. Since laminin is abundant in both the lungs and skin, we suggest that laminin binding is an important mechanism in P. aeruginosa pathogenesis.
Highlights
Pseudomonas aeruginosa efficiently adheres to human tissues, including the lungs and skin, causing infections that are difficult to treat
We have previously demonstrated that these strains have gained increased ability to bind vitronectin, a human complement regulator of the terminal pathway of the complement system, and an important component of the extracellular matrix (ECM)[4]
Pseudomonas aeruginosa isolated from cystic fibrosis (CF) patients have adapted to bind laminin
Summary
Pseudomonas aeruginosa efficiently adheres to human tissues, including the lungs and skin, causing infections that are difficult to treat. P. aeruginosa binds laminin via multiple surface receptors, and isolates from lungs of cystic fibrosis patients bound significantly more laminin compared to bacteria isolated from the skin and urine. Pseudomonas aeruginosa is a Gram-negative rod-shaped bacterial species with the ability to cause infections in almost every anatomical compartment of the human body Opportunistic infections by this species are common in situations with destroyed barriers, such as skin defects in chronic or burn wounds, or epithelial impairment in advanced stages of chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF)[1,2]. This is required in order to prevent trapping and removal by the respiratory mucus, as it is propelled towards the oropharynx by ciliary beating on bronchial epithelial cells[5]. It is mainly composed of proteoglycans such as heparan sulphate, soluble glycoproteins (vitronectin and fibronectin) and fibrous proteins (collagen, elastin and laminin)
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