Targeting Staphylococcus aureus Toxins: A Potential form of Anti-Virulence Therapy

Abstract

Staphylococcus aureus is an opportunistic pathogen and the leading cause of a wide range of severe clinical infections. The range of diseases reflects the diversity of virulence factors produced by this pathogen. To establish an infection in the host, S. aureus expresses an inclusive set of virulence factors such as toxins, enzymes, adhesins, and other surface proteins that allow the pathogen to survive under extreme conditions and are essential for the bacteria’s ability to spread through tissues. Expression and secretion of this array of toxins and enzymes are tightly controlled by a number of regulatory systems. S. aureus is also notorious for its ability to resist the arsenal of currently available antibiotics and dissemination of various multidrug-resistant S. aureus clones limits therapeutic options for a S. aureus infection. Recently, the development of anti-virulence therapeutics that neutralize S. aureus toxins or block the pathways that regulate toxin production has shown potential in thwarting the bacteria’s acquisition of antibiotic resistance. In this review, we provide insights into the regulation of S. aureus toxin production and potential anti-virulence strategies that target S. aureus toxins.

New Threats from an Old Foe: Methicillin-Resistant <b><i>Staphylococcus aureus</i></b> Infections in Neonates

“…The reduced susceptibility of vancomycin to MRSA poses a great challenge for anti-infective treatment of MRSA in neonates, as vancomycin is the empiric antibiotic of choice in neonates presenting with sepsis and extensive skin infections, especially in regions where the prevalence of MRSA is high [61, 62]. Approaches targeting virulent determinants of MRSA may be promising [50], with their efficacy and safety yet to be validated in the neonatal population. So far, the best strategy to manage neonatal MRSA infections lies in prevention rather than treatment.…”

“…MRSA produces a vast repertoire of toxins, including phenol-soluble modulins, leukotoxins (Panton-Valentine leukocidin, LukED, and LukAB/DH), hemolysins, exfoliative toxins, staphylococcal enterotoxins, and toxic-shock syndrome toxin-1 [50]. Toxins may contribute to MRSA persistence in the host, relapse of infections, tissue damage, and the production of proinflammatory cytokines [47, 51, 52].…”

Cloning and Expression of Alpha Hemolysin Toxin Gene of Staphylococcus aureus Against Human Cancer Tissue

“…Alpha-toxin is a pore-forming hemolytic toxin that brings about membrane damage to many types of mammalian cells. Alpha hemolysin toxin can be increased the productivity by cloning (Leng et al, 2011;Tavares et al, 2014;Gurnev and Netorovich, 2014;Kong et al, 2016). Alpha hemolysin toxin plays a role in inducing apoptosis in tumor cells, so it can be used as anticancer .…”

Phenotypic and Genotypic Determination of Antibiotic Resistances of Some Clinical Staphylococcus aureus Isolates

“…S. aureus'un özellikle antibiyotiğe dirençli izolatları, ağırlıklı olarak ağır sepsis ve septik şok ile sonuçlanan hastane infeksiyonlarında tedavi güçlü-ğüne yol açarak yüksek morbidite ve mortaliteye neden olmaktadır. Bu durum da dünya çapında sağlık üzerinde önemli bir yük oluşturmaktadır [1] .…”

“…S. aureus'un özellikle antibiyotiğe dirençli izolatları, ağırlıklı olarak ağır sepsis ve septik şok ile sonuçlanan hastane infeksiyonlarında tedavi güçlü-ğüne yol açarak yüksek morbidite ve mortaliteye neden olmaktadır. Bu durum da dünya çapında sağlık üzerinde önemli bir yük oluşturmaktadır [1] .Stafilokoklarda metisilin direnci, mecA geni tarafından kodlanan ve penisilin bağlayan protein 2a (PBP2a) olarak adlandırılan bir proteinin üretimi sonucu ortaya çıkar. Bu modifiye olmuş proteinin beta-laktam grubu antibiyotiklere afinitesi düşük olduğu için tüm beta-laktam ve beta-laktam türevi antibiyotiklere dirence neden olmaktadır [2] .…”