Virulence Factor Targeting of the Bacterial Pathogen Staphylococcus aureus for Vaccine and Therapeutics

Abstract

Background Staphylococcus aureus is a major bacterial pathogen capable of causing a range of infections in humans from gastrointestinal disease, skin and soft tissue infections, to severe outcomes such as sepsis. Staphylococcal infections in humans can be frequent and recurring, with treatments becoming less effective due to the growing persistence of antibiotic resistant S. aureus strains. Due to the prevalence of antibiotic resistance, and the current limitations on antibiotic development, an active and highly promising avenue of research has been to develop strategies to specifically inhibit the activity of virulence factors produced S. aureus as an alternative means to treat disease. Objective In this review we specifically highlight several major virulence factors produced by S. aureus for which recent advances in antivirulence approaches may hold promise as an alternative means to treating diseases caused by this pathogen. Strategies to inhibit virulence factors can range from small molecule inhibitors, to antibodies, to mutant and toxoid forms of the virulence proteins. Conclusion The major prevalence of antibiotic resistant strains of S. aureus combined with the lack of new antibiotic discoveries highlight the need for vigorous research into alternative strategies to combat diseases caused by this highly successful pathogen. Current efforts to develop specific antivirulence strategies, vaccine approaches, and alternative therapies for treating severe disease caused by S. aureus have the potential to stem the tide against the limitations that we face in the post-antibiotic era.

Targeting ESKAPE pathogens with anti-infective medicinal plants from the Greater Mpigi region in Uganda

“…Selectively inhibiting quorum sensing pathways could prove to be an efficient alternative to antibiotics that simply try to kill the pathogen. One advantage of targeting the agr system is disruption of a wide variety of virulence factors, instead of targeting each virulence factor individually 70,71 . Use of botanical formulations or small molecule quorum sensing inhibitors isolated from medicinal plants might offer some additional benefits, e.g.…”

Staphylococcal Enterotoxin C—An Update on SEC Variants, Their Structure and Properties, and Their Role in Foodborne Intoxications

“…Staphylococcal virulence factors include exopolysaccharides, surface-associated protein adhesins, immune modulators, and exoproteins including a variety of toxins [8]. Staphylococcal virulence factors [9,10] and their role in both infectious diseases [6,11] and food intoxications [12,13] have been previously reviewed. The most relevant secreted toxins are SEs, hemolysins, leukotoxins, exfoliative toxins, and toxic shock syndrome toxin (TSST-1) [14].…”

Contribution of anti-inflammatory and anti-virulence effects of azithromycin in the treatment of experimental Staphylococcus aureus keratitis

“…Secondly, although we tried to detect the bacterial toxins in the culture supernatant that were reduced by AZM using an immunoassay (data not shown), we could not identify these toxins. It is considered that AZM can suppress the production of pore-forming toxins, such as alpha-toxin and Panton-Valentine leucocidin, which are major virulence factors leading to corneal damage by S. aureus [5,[25][26][27]. The inhibition of bacterial virulence factors by AZM was not confirmed in vivo because the bacterial virulence factor influenced by AZM had not been identified in the in vitro study.…”