Targeting Surface Protein SasX by Active and Passive Vaccination To Reduce Staphylococcus aureus Colonization and Infection

Abstract

c SasX is a recently described surface protein of Staphylococcus aureus that is linked to the epidemic success of hospital-associated methicillin-resistant clones, in particular in Asia. It enhances nasal colonization and virulence in skin and lung infection models. Here, we evaluated the potential of SasX as a vaccine component in passive and active immunization efforts using mouse infection models. We found that SasX induced a specific immune response predominantly based on IgG1 antibodies. Active immunization with recombinant SasX or passive immunization with rabbit polyclonal anti-SasX IgG significantly decreased the size of lesions caused by S. aureus in a skin infection model. Furthermore, active immunization reduced acute lung injury in a lung infection model. Moreover, active or passive immunization significantly reduced S. aureus colonization in a nasal colonization model. Finally, anti-SasX IgG enhanced the susceptibility of S. aureus to killing by human neutrophils. We conclude that SasX is a potential target for therapeutics or vaccines designed to moderate colonization and infection by sasX-positive epidemic strains of S. aureus. Staphylococcus aureus is a major global source of morbidity and mortality (1), causing more than 11,000 deaths per year in the United States alone (2). It is particularly notorious as a dangerous hospital-associated pathogen. Treatment of S. aureus infections is severely complicated by antibiotic resistance (3). In particular, resistance to methicillin in methicillin-resistant S. aureus (MRSA), which in many countries occurs in more than half of infectious S. aureus isolates, is a major health care concern. In addition, many S. aureus strains are resistant to a wide variety of other antibiotics, leaving only very limited options for treatment. In an era that has seen a broad withdrawal of pharmaceutical companies from the much-needed development of novel antibiotics, researchers in companies and academia are again beginning to attempt vaccine development against S. aureus. A working vaccine against S. aureus infections is not available, and multiple reasons have been discussed for why an anti-S. aureus vaccine is difficult to find (4, 5). These include first and foremost the large arsenal of immune evasion factors of S. aureus, which target both acquired and innate immune defenses (6). However, there is promising evidence indicating that passive and active vaccination against S. aureus should in principle be possible, notwithstanding the fact that we still do not completely understand the mechanisms the immune system uses for protective immunity against S. aureus (4).Infective S. aureus and MRSA isolates are very diverse regarding geographical origin and time of isolation. Over the years, specific predominant MRSA clones arose and were thereafter replaced by others, in a scenario of epidemic waves (7). Furthermore, infections in different geographic areas are characterized by a divergent and often endemic composition of prevalent S. aureus and MRSA lineages. This situation ...

The Staphylococcal Biofilm: Adhesins, Regulation, and Host Response

“…SasX has recently been shown to be a promising vaccine candidate for S. aureus infection. Active or passive immunization to SasX decreased S. aureus virulence in murine models of skin infection, lung infection, and nasal colonization (152). …”

Regulation of saeRS, agrA and sarA on sasX Expression in Staphylococcus aureus

“…It is also a virulence factor during S. aureus skin and lung infection models (9). Anti-SasX IgG reduced S. aureus colonization and infection (10). However, the regulation mechanism of sasX is not clear.…”

Genotype Diversity and Evaluation of Biofilm Formation in sasX Positive Methicillin-Resistant Staphylococcus aureus

“…One of these important proteins is sasX that has many different roles in this process, including biofilm formation, which helps the bacteria in producing micro colonies and adhesion on the surfaces and bacterial resistance against unexpected conditions (11). Regarding recent studies, SasX had an important role in the pathogenesis of the asian population and ST239 colon (8) and based on its importance, even new studiese have focused on the role of SasX protein in immunization and vaccinaton (9). Furthermore, recent studies have shown that the sasX gene is spreading to other colonies and species (8,12).…”