**7. Discussion**

*S. aureus* is the main pathogenic species of its genus, and a common cause of various superficial and internal infections. Although some of this infection can be quickly resolved, this pathogen's current interest derives from its high frequency in life-threatening diseases such as sepsis, meningitis, or pneumonia by MDR-bacteria. The variability of *S. aureus* and the rapid adaptive response to changes in the environment and its continuous acquisition of antibiotic resistance determinants have made it a habitual resident of the hospital habitat and an important agent of HAIs. Since the main consequence of bacterial resistance is antibiotic therapy failure, the increase in morbidity and mortality, and the increase in medical care costs, it is essential to containing the problem. As MDRinfections with *S. aureus* increases worldwide to dangerous levels, the urgent search for new antimicrobial strategies is required. Complementary therapies and antimicrobial treatment options may help relieve pressure from multidrugresistant bacteria on healthcare systems. PDT then promises to be very useful to complement antibiotic treatment. The PDT is a noninvasive strategy, which uses inert compounds that need to be activated locally [6].

As we see in **Figure 1**, PDT's mechanism can change the internal and external structural integrity of bacterial cells and cause unspecific cell death. This process is closely related to the formation of ROS, without the generation of resistance. **Table 1**, shows the most widely used and explored SP are those derived from porphyrins since these present a high decrease in bacterial viability when irradiated. It should be noted that the irradiation to activate the photo-oxidative effect of PS is essential since the effectiveness of the treatment depends on this. The wavelength in the ranges of 620 to 700 nm is considered the most efficient technique as the red light manages to penetrate deep enough into the target tissue to produce its activity.

The BFs are important to point considering the pathogenicity of *S. aureus*. The PDT achieved the eradication of the BF in most investigations, but this disruption capacity was variable and is highly dependent on the technique used (the type of PS, type of irradiation, combination with antibiotics, among others). The decrease in bacterial survival in BF after PDT was much lower than observed for planktonic bacteria. The difference may radicate in the cell wall composition and growth rate, and the matrix components that hinder the photosensitizer absorption and light penetration.

The synergy with antimicrobials in combination therapy effectively increases microorganisms' sensitivity to the antibiotics of choice. In addition to avoiding a large amount of antibiotic use, this strategy minimizes the spread of resistance. On the other hand, a lower drug concentration can be used during combined therapy to reduce the side effects.

Genetics plays an important role, and PDT showed that it might generate a modulation in the genes associated with virulence. Promoting the silencing of gene expression, the PDT significantly decreases bacterial viability. In turn, the *agr* gene has been assigned a central role in the pathogenesis of *S. aureus*. Its down-regulation may affect colonization factors, components of the microbial surface, and the formation of BF that are regulated by *agr* gene.
