Staphylococcus aureus is responsible for several infections, from boils to sepsis, which can cause death [1]. The conventional treatment is carried out by administering antibiotics. However, indiscriminate use is responsible for the emergence of resistant bacteria. Strains of S. aureus resistant to several antibiotics have already been described, the most clinically important being methicillin-resistant Staphylococcus aureus (MRSA) [2].

The Center for Disease Control and Prevention (CDC) identified in 2019 that the rate of MRSA strains exceeded 41% among adults and 28% among pediatric patients, with approximately 323,700 cases and reaching about 10,600 deaths, resulting in 1.7 billion dollars in expenses [3]. These high mortality rates in hospitalized patients have caused worldwide concern.

In 2017, a list of the 12 bacteria most at risk to human health due to their high resistance was divided into three categories of urgency, in which MRSA was reported as a high priority [4]. In 2019, WHO reinforced the alert about the shortage of developing new antibiotics for MRSA. Currently, only seven antibiotics are in the preclinical phase for treating these infections, but with no prediction of applicability, reinforcing the importance of alternatives to antibiotic therapy [4]. Among these alternatives, antimicrobial photodynamic therapy (aPDT) stands out due to its effectiveness and not generating antimicrobial resistance.

The aPDT comprises the association of a photosensitizer (PS), which, after interacting with the cell, is excited by light with a wavelength appropriate to that PS, reacting with molecular oxygen and forming reactive oxygen species (ROS), responsible for cell inactivation [[5], [6], [7]]. ROS can cause bacterial cell death instead of inhibiting their growth, reducing the chances of microorganisms developing tolerance or resistance to aPDT [7]. Photodithazine® (PDZ) is an e6 chlorin of Russian origin, obtained from the cyanobacterium Spirulina platensis, demonstrating a high ROS production when irradiated [8,9].

Therefore, additional studies are needed to evaluate the application of aPDT with PDZ, both in vitro and in vivo, as an alternative to antibiotic therapy. Invertebrate models for in vivo research stand out due to the ease of handling and the size of the larvae, allowing the injection of substances directly into the hemolymph, which will be collected to be analyzed. In addition, they have an innate immune system with the action, mainly, of hemocytes with a similar function to the neutrophils of mammals, as is the case of the species Galleria mellonella, thus allowing us to understand both the effect of the bacteria in the organism and the impact of the action of aPDT with PDZ in MRSA strains [[10], [11], [12]]. It is important to emphasize that invertebrate models have limitations and do not reflect the complexity of mammalian systems. However, carrying out studies in invertebrates beforehand leads to a decrease in the use of animals for further study in mammals. This study aimed to assess the impact of PDZ-mediated aPDT on multiresistant Staphylococcus aureus (MRSA) through two stages: i) in vitro testing to determine its effectiveness in inactivating mature biofilms with a high density of sessile cells to mimic the challenge of eliminating a biofilm in the absence of the immune system, as in industrial biofouling; and ii) in vivo testing, to assess the effectiveness of aPDT in treating MRSA infection in larvae of Galleria mellonella, which serve as an in vivo model possessing an immune system. The findings from this work will aid in determining the applicability of general or specific aPDT conditions for eliminating biofilms on abiotic surfaces or those related to bacterial infection.