**1. Introduction**

Staphylococci are a large group of gram-positive cocci, whose diameter varies from 0.5 to 1.5 μm whose grouping resembles grape Clusters. To date, 35 known species and 17 subspecies of the genus *Staphylococcus* have been reported [1]. *Staphylococcus aureus* (*S. aureus*) is a bacterium with wide dissemination; Although it is part of the human body's commensal microbiota, it can cause severe skin infections, localized abscesses, and also may cause osteomyelitis, endocarditis, and other life-threatening diseases. Also, *S. aureus* has become a significant cause of healthcare-associated infections (HAIs) [2]. Besides, *S. aureus* acts as an early colonizer, creating a favorable environment for the adhesion and colonization of bacteria producing biofilms (BF). BFs consist of an array of proteins and polysaccharides that form an extracellular matrix (**Figure 1**). This matrix is considered an essential virulence factor of *S. aureus* strains, as it functions as a barrier against antimicrobial agents and the host's immune system, helping to maintain bacterial colonization [3, 4].

Since the discovery of antibiotics and their application, many bacterial infections have been successfully treated. However, in recent years the resistance of bacteria to antibiotics is emerging and increasing rapidly. *S. aureus* has progressively

**Figure 1.**

*Target structures from the Gram+ envelope for Photodynamic inactivation. Photodynamic therapy generates ROS that acts unspecifically on macromolecules present in the envelope of Gram + bacteria, such as lipids and proteins of the plasma membrane, peptidoglycan of the cell wall, and the array of proteins and polysaccharides macromolecules of the matrix that forms the biofilm.*

gained multiple resistance to antibiotics, such as penicillin, methicillin, and other multiple drugs, leading to infections with frustrated or ineffective antibiotic therapies [5, 6]. The scarce development of new antibiotic added to the progressive increasing in multidrug-resistance of this and other clinically relevant bacteria has been considered by the World Health Organization (WHO) as one of the most pressing global threats to human health in the 21st century and described the situation as a global crisis and impending catastrophe of a return to the pre-antibiotic era. In this regard, the WHO published a list of microorganisms that should be investigated with priority to generate new antimicrobial drugs [7]. According to this list, *S. aureus,* with resistance to methicillin or vancomycin, is ranked second with high priority [7].

*S. aureus* displays various resistance mechanisms; for example, resistance to penicillin is mediated by hydrolytic enzymes called beta-lactamases. Betalactamases confer resistance to all penicillins except isoxazolyl penicillins (oxacillin, methicillin, cloxacillin, and nafcillin), as well as sensitivity to combinations of beta-lactams with beta-lactamase inhibitors (clavulanic acid, tazobactam, and sulbactam), or cephalosporins and carbapenems [8]. Resistance to methicillin, nafcillin, and oxacillin is independent of beta-lactamase production. This resistance is mediated by the *mec*A gene acquisition, which is translated into a new penicillinbinding protein (PBP2a). PBP2a decreases *S. aureus*'s affinity for methicillin and, therefore, allows it to survive treatments with this antibiotic [9]. Strains of *S. aureus* that express the *mec*A gene are called methicillin-resistant *S. aureus* (MRSA). MRSA strains are resistant to all beta-lactams (except 5th generation cephalosporins) and usually to aminoglycosides, erythromycin, clindamycin, tetracyclines, sulfonamides, quinolones, and rifampicin. While colonization of MRSA in a healthy

*Photodynamic Treatment of* Staphylococcus aureus *Infections DOI: http://dx.doi.org/10.5772/intechopen.95455*

individual is generally not serious, it can be life-threatening for patients with deep wounds, intravenous catheters, or other invasive instruments, as well as secondary infections in patients with a weakened immune system. Following the guidelines of the Clinical and Laboratory Standards Institute (CLSI), there are strains of *S. aureus* that present low-level or borderline resistance, for example, to oxacillin (BORSA) or vancomycin (VISA). The BORSA is characterized by a minimum inhibitory concentration (MIC) of oxacillin at the resistance cut-off point (4 mg / L) or a dilution above it [8]. *S. aureus* may present resistance to glycopeptides when it presents a MIC of vancomycin (VAN) of 4–8 mg/L. Furthermore, it is considered resistant with a MIC of NPV ≥ 16 mg/L [10]. The MIC should be determined using the broth microdilution method, according to CLSI.

Due to all those mentioned above, there is a challenge in urgently searching for new antimicrobial approaches to treat bacteria without producing resistance to antibiotics. Several new strategies have been developed, such as metallic nanoparticles, cationic polymers, peptidoglycans, nanocarriers, photothermotherapy and photodynamic therapy (PDT). Due to its demonstrated antitumor activity, PDT has been strongly developed to treat cancer, although not so much in its antimicrobial activity. Some studies have shown that PDT successfully reduces the biological activity of specific virulence factors produced by Gram-negative strains, and therefore, the analysis of the efficacy of this therapy in Gram-positive bacteria is essential [3, 4].

PDT is based on the use of photosensitizer molecules (PS) that produce local cytotoxicity after being activated by light (photo-oxidative stress). PS compounds absorb energy from visible light of a specific wavelength and transfer it to molecular oxygen, producing reactive oxygen species (ROS). **Figure 2** shows the mechanism for ROS production, which could be by electron transfer (e-) to produce superoxide (O2 •−) or by energy transfer, which produces highly reactive singlet oxygen (1 O2). ROS production induces nonspecific bacterial death [12].

Very few initiatives have studied the information described to date on PDT antimicrobial therapy against *S. aureus* infections, and a bibliographic exploration of this strategy is relevant. The present review is a bibliographic study of the information available on the application of PDT against strains of *S. aureus* with particular

#### **Figure 2.**

*The extraordinary power of the PSs. The basal state of PS is with two opposite lower energy molecular spin e-. The irradiation must penetrate the tissues deep enough to deliver enough energy to excite an e- to a higher energy orbital. An intersystem crossover can reach the excited state to a triplet state, where the excited e- spin is reversed. Excited triplet can produce two types of reactions: Type I and Type II. Type I: the excited triplet state can gain an e- from a nearby reducing agent, oxidizing it, producing H2O2. Type II: the excited triplet state transfers its energy directly to molecular oxygen, forming 1 O2. The type II reaction provides most of the photooxidative stress. 1 O2 is a ROS that produces concerted addition reactions to groups of alkenes present in organic molecules such as proteins, lipids o nuclear acids leading to nonspecific bacterial death. The generation of <sup>1</sup> O2 will be effective, taking into account the PS, where its excited states have a longer half-life. It is essential to improve the probability of interacting with triple oxygen and producing 1 O2 [11].*

emphasis on *S. aureus* sensitive to multiple drugs (MDSSA); *S. aureus* multi-drug resistant strains (MDRSA); Methicillin-sensitive *S. aureus* (MSSA) and MRSA.
