**1.2 History of bacterial EVs**

The first study regarding bacterial EVs dates back to 1966, when lipid-like structures purified from culture supernatants of *Escherichia coli* were observed under electron microscopy [9]. In Gram-negative bacteria, vesiculation occurs from the budding out of the outer membrane (OM) that captures components present in the periplasm. This process forms nanoparticles called outer membrane vesicles (OMVs), which are released in the extracellular milieu [10]. Gram-positive bacteria lack an outer membrane and have a thicker peptidoglycan (PGN) cell wall, which was regarded as a barrier to EV release. This might explain why the first observations of EV release in Gram-positive bacteria were reported much later, in 2009,

*Extracellular Vesicles and Their Role in* Staphylococcus aureus *Resistance and Virulence DOI: http://dx.doi.org/10.5772/intechopen.96023*

when Lee and collaborators demonstrated the production of EVs by *Staphylococcus aureus* [11]. Ever since, other studies confirmed EVs release by other Gram-positive bacteria belonging to various genera such as *Bacillus sp*, *Bifidobacterium sp*, *Cutibacterium sp*, *Clostridium sp*, *Enterococcus sp*, *Lactobacillus sp*, *Mycobacterium sp*, *Propionibacterium sp*, and *Streptococcus sp*, among others [12–22].

### **1.3** *S. aureus* **and its derived EVs**

*S. aureus* is a bacterium that asymptomatically colonizes the nasal track of 20–80% of the human population without causing disease [23]. *S. aureus* is also a major opportunistic pathogen in humans, being a common cause of nosocomial infections [24]. It is a causative agent of life-threatening diseases such as sepsis, endocarditis, pneumonia, and minor infections in soft tissues [25]. *S. aureus* is also an important pathogen in veterinary medicine. It is one of the main etiological agents of mastitis, an inflammation of the mammary gland that affects dairy herds and causes vast economic losses worldwide [26]. The type and severity of infections depend on strain-specific virulence factors, mostly expressed from accessory genetic elements [27]. Secreted and surface-exposed *S. aureus* virulence factors are responsible for weakening the host immune response, immune evasion, damage to host tissues, and infection onset [28].

One emerging field of great interest is the involvement of EVs in the infections caused by *S. aureus*. Recent studies have shown that *S. aureus* EVs carry important bacterial survival and virulence factors, such as β-lactamases, superantigens, toxins, coagulases, and proteins associated with bacterial adherence to host cells [11, 29–34]. In some cases, they trigger production of cytokines and promote tissue inflammation [35–38]. As EVs are also regarded as potential vehicles for biotechnological and clinical applications, such as the development of vaccines [39–42], their study is an attractive area in microbiology and the future development of new strategies against bacterial infections. Here, we will address the main studies regarding *S. aureus* EVs, their biogenesis, composition, and roles in bacterial resistance, virulence, host-pathogen interactions, and the possible applications of EVs for diagnostic, therapy, and vaccine development against diseases caused by this bacterium (see **Figure 1**).
