Binding of a Cytopathic or an Invasive Strain of p. Aeruginosa to Cytoskeletal, Basement Membrane, or Matrix Proteins of Wounded Cornea is Similar and does not Rely on Interaction with Actin Filaments

Abstract

Pseudomonas aeruginosa is a typically opportunistic bacterium. Although it is widely distributed in human biology and produces numerous virulence-associated factors, P. aeruginosa does not infect human tissues unless the normal host defense mechanisms have been impaired. The bacteria does not exhibit tissue specificity, shown by many human pathogens; it infects tissues of diverse origins but only ones that have been damaged in some way. Why the affinity for damaged tissues by this organism remains unanswered. In this regard, several studies have examined P. aeruginosa adherence to unmasked extracellular matrix (ECM) following tissue damage in both human^1,2 and experimental³ systems. Tissue damage may result in exposure of the basement membrane, which consists mainly of collagen (Type IV) and glycoproteins such as fibronectin (FN), laminin (LN), and heparan sulfate proteoglycan. P. aeruginosa has been shown to bind to soluble FN, but not to polymerized cellular or plasma FN,⁴ and to laminin.⁵ But simply being able to adhere or even being able to enter a host cell is not sufficient, and pathogenicity usually exhibits a multifactoral phenotype.⁶ Pili are the major adhesin by which P. aeruginosa interacts with mammalian host tissue,⁷ but studies have shown that pilusdeficient mutants of P. aeruginosa bind to respiratory mucus⁸ and to corneal epithelium⁹ as well as to other non-epithelial cell types.¹⁰ Binding to laminin, for example, may involve a noo-pilus adhesion from the bacterial outer membrane.⁵ It also has been shown that bacterial elastase and alkaline protease cleave soluble laminin,¹¹ providing for tissue invasion and hemorrhagic tissue necrosis, as well as exposure of lipase-sensitive receptors, allowing enhanced bacterial bingiding to the corneal epithelium.¹²