Pneumonia caused by Staphylococcus aureus constitutes 1%–10% of cases of community-acquired
pneumonia and around 20% of cases of hospital acquired pneumonia (HAP). The emergence of antibiotic
resistance, especially to methicillin among nosocomial strains, resulted in difficulties in treatment, which is
then responsible for prolonged hospital stays, increased mortality and morbidity of infections. The rates of
methicillin resistance among clinical isolates vary from country to country, ranging from a small percent in
Scandinavian countries to ~50-75% in the U.S. and Asian countries. Additionally, biofilm formation on
patient’s tissues plays important role in S. aureus virulence as bacteria in biofilm are more resistant eradication.
Furthermore, as individual cells detach from mature biofilm and establish new sites of infection or mediate an
acute infection such as sepsis. Bacteriophages, the viruses that infect bacteria, have been shown to be able to
successfully eradicate biofilm. Phages can prevent biofilm formation and maturation by destroying bacteria in
the outer layer of biofilm. They can also penetrate into biofilm matrix and break down biofilm its structure as
phage lytic enzymes, depolymerase and lysins, are being released from the cells upon phage progeny release.
However, even phages have their limitations. Therefore, it is currently recommended to pair bacteriophages
with other antimicrobials. Since the global consensus is to reduce the use of antibiotics, other compounds with
antimicrobial activity are being considered. Lactoferrin, an 80 kDa protein of the transferrin family is an
important part of the innate immune system. It is present in the blood, at the mucosa, and it is secreted with
fluids such as milk, tears or sweat. It has been shown that lactoferrin can act as anti-biofilm agent reducing the
biomass, loosening the biofilm structure and enabling its dispersion. In our previous works we have paired 1.0
mg/ml of lactoferrin with 109 PFU/ml of staphylococcal bacteriophages and have observed that the
combination was effective in reducing biofilm biomass and biofilm metabolic activity in vitro. This project is
intended to be a first step of a complex study that aims to assess the safety and efficacy of phage therapy in
MRSA respiratory tract infections. Using already isolated and characterized bacteriophages with proven
antibacterial activity mixed with lactoferrin it intends to test the influence of phages on metabolic state and
membrane integrity of human lung epithelial cells (line A549) in order to assess if phages pose no harm to the
cells.