Ricerc@Sapienza

One of the main causes of microbial keratitis is the improper use of soft contact lenses (CLs). This is because CLs can be colonized and infected by different types of microorganisms, such as Pseudomonas aeruginosa or Staphylococcus aureus. These pathogens are opportunistic microorganisms that are able to directly damage the corneal tissue leading to its perforation. They can adhere to the CLs surface forming biofilms. In additions, they have the ability to easily develop resistance to conventional antibiotics, making treatment of the infection often useless. In this scenario, new compounds capable of eradicating microbial infections, but also new strategies able to reduce lens colonization are highly necessary. Thanks to their interesting biological properties, antimicrobial peptides (AMPs) have attracted the attention of scientific research as candidates for the development of new antibacterial compounds. This is due to their membrane-perturbing mechanism of action that very rarely leads to resistance. AMPs have recently been characterized not only by their antibacterial properties, but also by a series of immunomodulatory functions. It has recently been demonstrated that two derivatives of the frog-skin esculentin-1a, named Esc(1-21) and Esc(1-21)-1c, have a potent anti-pseudomonal activity with immunomodulatory properties. Furthermore, Esc(1-21) was found to cause significant bacterial clearance in mouse models of keratitis. Another class of AMPs includes temporins, e.g. TA and TB, active especially against Gram-positive bacteria. These peptides are able to stimulate migration of keratinocytes and to kill intracellular S. aureus. Nevertheless, a relevant aim that needs to be achieved for the usage of AMPs in therapy includes the increase of their half-life and reduction in cytotoxicity. A promising strategy to reach these goals is given by peptides immobilization on CLs. The project will mainly focus on the biological characterization of peptide-coated CLs.